Teratogenicity of Valproic Acid: Can Reverse its Possible Effects on Testicular Development with Vitamin E? / Teratogenicidad del Ácido Valproico: ¿Se Pueden Revertir sus Posibles Efectos sobre el Desarrollo Testicular con la Vitamina E?

Epilepsy is the chronic non-communicable disease of the nervous system most prevalent in the world. Valproic acid (VPA) is one of the most used drugs in the treatment of epilepsy but with various side effects. One of the organs that can be affected is the testis, where it has been seen that men treated with VPA reduce their fertility rates, in addition to causing endocrine disorders by decreasing androgens and gonadotropins. In animal models, it has been shown to reduce the weights of the glands attached to the male reproductive tract, as well as at the testicular level, decreasing sperm concentration and increasing apoptotic cell count. These effects are because VPA increases reactive oxygen species (ROS), causing damage to macromolecules and affecting all cellular processes sensitive to oxide reduction. Throughout testicular development, in utero, it has been seen that the expression of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase, are lower during early embryonic development, as well as vitamin E (VE) is decreased. Therefore, they are not sufficient to reverse the toxic effects of ROS. The objective of this study was to review the use of VPA during pregnancy, its effect on testicular development, and to explore the potential protective role of vitamin E.

La epilepsia es una enfermedad crónica no transmisible que afecta al sistema nervioso más prevalente en el mundo. Dentro de los tratamientos, uno de los fármacos más utilizados es el ácido valproico (AVP), el que ocasiona diversos efectos secundarios. Entre los órganos que se pueden ver afectados se encuentra la gónada masculina, en donde se ha visto que hombres en tratamiento con AVP reducen sus tasas de fecundidad, además de causar trastornos endocrinos disminuyendo andrógenos y gonadotrofinas. En modelos animales, se ha visto que disminuye los pesos de las glándulas anexas al tracto reproductor masculino, como también a nivel testicular, disminuyendo la concentración espermática y aumentando el recuento de células apoptóticas. Estos efectos se deberían a que el AVP aumenta las especies reactivas de oxígeno (ROS), ocasionando daño en macromoléculas, afectando todos los procesos celulares sensibles a óxido reducción. A lo largo del desarrollo testicular, in utero se ha visto que la expresión de enzimas antioxidantes como superóxido dismutasa, catalasa y glutatión peroxidasa, son más bajos durante el desarrollo embrionario temprano, como también la vitamina E (VE) se encuentra disminuida. Por tanto, no resultan suficientes para revertir los efectos tóxicos de las ROS. El objetivo de esta revisión fue asociar el uso de AVP durante la gestación y sus efectos a nivel del desarrollo testicular y describir el potencial rol protector de la VE.

Efecto de la Vitamina E en Células Peritubulares de Testículos de Ratones Mus musculus Tratados con Ácido Valproico Durante el Estado Fetal y Pubertad / Effect of Vitamin E on Peritubular Cells from Testis of Mus musculus Mice Treated with Valproic Acid During the Fetal Stage and Puberty

El ácido valproico (VPA) es un fármaco antiepiléptico teratógenico que, al ser administrado durante etapas tempranas del embarazo, puede producir alteraciones en el desarrollo embriofetal, las que se manifiestan tanto a nivel del sistema nervioso como del testículo. No obstante, se ha reportado que la administración de vitamina E (VE) podría revertir dichas alteraciones. El objetivo del presente estudio fue determinar el efecto protector de la VE a nivel testicular en fetos y ratones púberes expuestos a VPA durante la fase embrionaria de su desarrollo. Se utilizó un total de 30 ratones hembra adultas gestantes (Mus musculus) cepa BALB/c, las cuales se dividieron en 6 grupos. El estudio contempló el análisis de fetos machos a los 17,5 días post-coital (dpc) y machos juveniles a las 6 semanas post-natal. A los grupos 1 y 4 se les administró 0,3 mL de solución fisiológica (grupos control para 17,5 dpc y 6 semanas postnatal, respectivamente). A los grupos 2 y 5 se les suministró la cantidad de 600 mg/kg de VPA (grupos VPA), en tanto que a los grupos 3 y 6 se les aplicó la misma dosis de VPA complementada con 200 UI de VE (grupos VPA+VE). Se describió la histología normal y patológica del compartimento peritubular del testículo. En los grupos VPA se evidenció una degeneración de la pared peritubular, y atrofia de túbulos seminíferos, así como exfoliación de las células germinales. Por el contrario, en los grupos VPA+VE tales signos no fueron observados y la morfología presentó aspecto normal solo con algunas alteraciones focales. Estos resultados corroboran el hecho que la administración de VE contrarresta en parte, los efectos deletéreos que ocasiona el VPA.

SUMMARY: Valproic acid (VPA) is a teratogenic antiepileptic drug that, when administered during the early stages of pregnancy, can produce alterations in embryo-fetal development, which manifest both at the level of the nervous system and the testicle. However, it has been reported that the administration of vitamin E (VE) could reverse these alterations. The study aimed to determine the protective effect of VE at the testicular level in fetuses and pubertal mice exposed to VPA during the embryonic phase of their development. 30 pregnant adult female mice (Mus musculus) BALB/c strain were used, which were divided into 6 groups. The study included the analysis of male fetuses at 17.5 days post-coital (dpc) and juvenile males at 6 weeks post-natal. Groups 1 and 4 were administered 0.3 mL of physiological solution. Groups 2 and 5 were given 600 mg/kg of VPA (VPA groups), while groups 3 and 6 were given the same dose of VPA supplemented with 200 IU of VE (VPA+VE). The normal and pathological histology of the peritubular compartment of the testis was described. In the VPA groups, degeneration of the peritubular wall, and atrophy of the seminiferous tubules, as well as exfoliation of the germ cells, were evident. On the contrary, in the VPA+VE groups such signs were not observed and the morphology presented a normal appearance with only some focal alterations. These results corroborate the fact that the administration of VE partially counteracts the deleterious effects caused by VPA.

Preparation of an ophthalmic formulation of TPGS-modified insulin-loaded liposomes and its in vitro corneal permeation and pharmacokinetics in rabbit eyes / 南方医科大学学报

OBJECTIVE@#To prepare vitamin E polyethylene glycol 1000 succinate (TPGS)-modified insulin-loaded liposomes (T-LPs/INS) and evaluate its safety, corneal permeability, ocular surface retention and pharmacokinetics in rabbit eyes.@*METHODS@#The safety of the preparation was investigated in human corneal endothelial cells (HCECs) using CCK8 assay and live/dead cell staining. In the ocular surface retention study, 6 rabbits were randomized into 2 equal groups for application of fluorescein sodium dilution or T-LPs/INS labeled with fluorescein in both eyes, which were photographed under cobalt blue light at different time points. In the cornea penetration test, another 6 rabbits divided into 2 groups for application of Nile red diluent or T-LPs/INS labeled with Nile red in both eyes, after which the corneas were harvested for microscopic observation. In the pharmacokinetic study, 2 groups of rabbits (n=24) were treated with eye drops of T-LPs/INS or insulin, and the aqueous humor and cornea were collected at different time points for measurement of insulin concentrations using enzyme linked immunosorbent assay. DAS2 software was used to analyze the pharmacokinetic parameters.@*RESULTS@#The prepared T-LPs/INS showed good safety in cultured HCECs. Corneal permeability assay and fluorescence tracer ocular surface retention assay demonstrated a significantly higher corneal permeability of T-LPs/INS with a prolonged drug residence in the cornea. In the pharmacokinetic study, insulin concentrations in the cornea at 6, 15, 45, 60, and 120 min (P < 0.01) and in the aqueous humor at 15, 45, 60, and 120 min after dosing were significantly higher in T-LPs/INS group. The changes in insulin concentrations in the cornea and aqueous humor were consistent with a two-compartment model in T-LPs/INS group and with the one-compartment model in the insulin group.@*CONCLUSION@#The prepared T-LPs/INS shows an improved corneal permeability, ocular surface retention capacity and eye tissue concentration of insulin in rabbits.

In vitro approaches to antioxidant screening for the development of a sunscreen formulation

Abstract The incorporation of antioxidants into sunscreens may provide additional skin photoprotection against the harmful photobiological effects of ultraviolet radiation. The present study evaluated the applicability of a screening approach to the assessment of the antioxidant and photoprotective properties of vitamin C, vitamin E, and coenzyme Q10 and then determined the performance of the most effective antioxidant in a sunscreen formulation. Antioxidant activity was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, 2,2`-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and oxygen radical absorbance capacity (ORAC) assay, and the photoprotective potential was investigated by the yeast photoprotection assay. The antioxidant with the best effect was incorporated into sunscreen formulations which were evaluated for 120 days regarding their in vitro photoprotective parameters. Vitamin C showed high antioxidant capacity as well as a photoprotective potential against simulated solar irradiation applied for times longer than 1 h. Although the Sun Protection Factor, UVA/UVB ratio and critical wavelength did not differed significantly (p<0.05) between the formulation blank and the formulations containing 0.5% or 1% vitamin C, formulations with vitamin C kept their photostability for 6 months. Consequently, the proposed screening approach seems to be promising for the development of an antisolar photostable formulation containing vitamin C as an antioxidant.

Desafios terapêuticos da mucosite oral em oncopediatria / Therapeutic challenges of oral mucositis in pediatric oncology

O Neuroblastoma (NB) é uma neoplasia do sistema nervoso simpático, e o segundo tumor sólido maligno extracraniano mais comum da infância. Na terapia antineoplásica, complicações orais podem ser observadas, dentre elas a mucosite oral (MO). Trata-se de uma inflamação aguda da mucosa, proveniente da toxicidade dos quimioterápicos. Este relato de caso enfatiza o manejo da MO, bem como sua influência na condição sistêmica e qualidade de vida. Paciente do sexo feminino, nove anos, apresentou recidiva de NB metastático, após tratamento de primeira linha. Admitida na unidade hospitalar para tratamento oncológico na enfermaria de pediatria oncológica, queixando-se de dor intensa em cavidade bucal e orofaringe, associada a pancitopenia severa febril. Ao exame físico apresentava disfagia e déficit ponderal grave, que debilitava a deglutição da própria saliva. O exame intraoral revelou lesões de MO grau 3, segundo a Organização Mundial de Saúde (OMS), em lábios, gengiva anterior e orofaringe. O tratamento consistiu em remoção de debris local, higiene da cavidade bucal com clorexidina 0,12% e utilizando haste flexível de algodão estéril tipo "Swab", visando controle microbiano local, diariamente. Além disso, foi aplicado no leito eritematoso e hemorrágico fotobiomodulação (660 nm, 50 mW, 2 J/cm2, 90 segundos) pontualmente nas áreas do leito da lesão e em varredura na região de orofaringe (sessões intercaladas). Foi prescrito acetato de racealfatocoferol (vitamina E) para ação antioxidante e hidratação dos lábios. Concomitante a mucosite, a paciente apresentou pancitopenia febril severa, sendo necessário uso de cefepima 150 mg/kg/dia, com coleta prévia de hemoculturas, fator estimulador de colônias de granulócitos, Fluconazol, hidratação e suporte nutricional. As hemoculturas foram negativas. As consequências da mucosite contribuíram para desnutrição e piora da qualidade de vida. Conclui-se que a intervenção odontológica em interdisciplinaridade, possibilitou o restabelecimento físico e emocional, possibilitando melhor uma qualidade de vida da paciente (AU).

Neuroblastoma (NB) is a neoplasia of the sympathetic nervous system and the second most common extracranial malignant solid tumor in childhood. In antineoplastic therapy, oral complications can be observed in antineoplastic therapy, among them oral mucositis (OM). It is an acute mucosa inflammation resulting from the toxicity of chemotherapy drugs. This case report emphasizes the management of OM and its influence on the systemic condition and quality of life. A female patient, nine years old, presented a recurrence of metastatic NB after first-line treatment. She was admitted to the hospital unit for oncological therapy in the pediatric oncology ward, complaining of severe pain in the oral cavity and oropharynx associated with severe febrile pancytopenia. On physical examination, she presented dysphagia and severe weight deficit, which weakened the swallowing of her saliva. According to the World Health Organization (WHO), the intraoral exam revealed third-grade OM lesions on the lips, anterior gum, and oropharynx. Treatment consisted of removing local debris, cleaning the oral cavity with 0.12% chlorhexidine, and using a flexible, sterile cotton swab, aiming for daily local microbial control. In addition, photobiomodulation (660 nm, 50 mW, 2 J/cm2, 90 seconds) was applied to the erythematous and hemorrhagic bed, punctually in the areas of the lesion and sweeps in the oropharynx region (interspersed sessions). Racealphatocopherol acetate (vitamin E) was prescribed for antioxidant action and lip hydration. Concomitant with mucositis, the patient had severe febrile pancytopenia, requiring cefepime 150 mg/kg/day, with previous collection of blood cultures, granulocyte colony-stimulating factor, fluconazole, hydration, and nutritional support. Blood cultures were negative. The consequences of mucositis contributed to malnutrition and worsened quality of life. It is concluded that the interdisciplinary dental intervention enabled physical and emotional restoration, enabling a better quality of life for the patient (AU).

Estado nutricional de vitamina E e fatores de risco cardiovascular em adultos e idosos: estudo Brazuca Natal / Nutritional status of vitamin E and cardiovascular risk factors in adults and elderly people: Brazuca Natal study

Introdução: As doenças cardiovasculares (DCV) são a principal causa de morbimortalidade no mundo. Diante disso, são estudadas estratégias de prevenção e tratamento de eventos cardiovasculares. Dentre elas, a vitamina E destaca-se por suas propriedades antioxidantes e anti-inflamatórias, apoiado por descobertas de que maior ingestão dietética de vitamina E e maiores concentrações de α-tocoferol (α-TOH) sérico estão associados com menor risco de eventos cardiovasculares. Com isso, dados sobre o estado nutricional de vitamina E da população e a sua relação com os fatores de risco cardiovascular são estratégias importantes para subsidiar programas e políticas públicas voltadas a prevenção e tratamento das DCV. Objetivo: Avaliar o estado nutricional de vitamina E e a relação com fatores de risco cardiovascular em adultos e idosos do Estudo Brazuca Natal. Métodos: Trata-se de um estudo de diferentes métodos. 1) A revisão narrativa que investigou na literatura estudos populacionais sobre a relação da vitamina E e as DCV, buscando compreender se a deficiência de vitamina E (DVE) também deve ser considerada um problema de saúde pública. 2) Estudo transversal que se decompõe, a partir das variáveis dependentes, em dois artigos científicos. O primeiro artigo desse estudo buscou avaliar a prevalência de DVE e os fatores de risco cardiovascular que estão associados ao status do α-TOH sérico em adultos e idosos do estudo Brazuca Natal. Análise de regressão linear múltipla foi realizada entre o αTOH sérico (variável dependente) e fatores de risco cardiovascular. O segundo artigo do estudo transversal objetivou avaliar o consumo de vitamina E, e identificar as principais fontes alimentares consumidas do micronutriente pela população avaliada. Para tanto, foram analisadas as condições socioeconômicas e demográficas (sexo, idade, cor/raça, escolaridade, renda per capita e distrito sanitário de moradia) e o consumo alimentar de vitamina E (variável dependente). Resultados: Na revisão narrativa foi observado que a DVE pode ser um problema de saúde pública, por ocorrer uma variação de 0,6% a 55,5% de DVE em todo o mundo, com percentuais mais elevados na Ásia e na Europa, onde se destacam as elevadas taxas de mortalidade por DCV. Estudos populacionais sugerem efeitos protetores da vitamina E nas DCV, porém, estudos de intervenção com suplementação de α-TOH não confirmaram a sua ação cardioprotetora. No artigo 2 do estudo transversal foi observado que 24,8% dos adultos e idosos de Natal apresentavam DVE e 89% apresentaram baixas concentrações de αTOH circulante (abaixo de 30 µmol/L). Verificamos que as pessoas do sexo feminino tinham maiores valores médios de α-TOH sérico. Além disso, o índice de adiposidade visceral elevado e maiores valores do escore de risco global foram associados a maiores concentrações de α-TOH sérico. O artigo 3 demonstrou que 95,7% dos indivíduos apresentavam baixa ingestão de vitamina E, considerando a Estimated Average Requirement (EAR) de 12 mg/dia, com menores valores de ingestão em indivíduos acima de 40 anos, mulheres, naqueles com renda per capita menor que um salário-mínimo e com menor escolaridade. O óleo de soja, polpa de açaí e carne vermelha forneceram o maior teor de vitamina E ingerida. Conclusão: A partir da revisão narrativa, foi demonstrado que a DVE pode ser um problema de saúde pública. O estudo transversal observou uma elevada prevalência de DVE na população estudada, em que o sexo, o índice de adiposidade visceral e o escore de risco global estão associados ao α-TOH sérico. Além disso, foi observado um baixo consumo de vitamina E, principalmente, em indivíduos mais velhos, mulheres e com baixa condição socioeconômica. A maior parte da vitamina E consumida era proveniente do óleo de soja, polpa de açaí e carne vermelha, destacando-se também a vitamina E proveniente de alimentos ultraprocessados, principalmente, na população de menor renda (AU).

Introduction: Cardiovascular diseases (CVD) are the principal cause of morbidity and mortality in the world. Therefore, experts have studied strategies for preventing and treating cardiovascular events. One of this knowledge is vitamin E stands out for its antioxidant and anti-inflammatory properties, supported by findings that higher dietary intake of vitamin E and higher concentrations of serum α-tocopherol (α-TOH) are associated with a lower risk of cardiovascular events. Therefore, data on the nutritional status of vitamin E in the population and its relationship with cardiovascular risk factors are relevant strategies to support programs and public policies aimed at preventing and treating CVD. Objective: To evaluate the nutritional status of vitamin E and its association with cardiovascular risk factors in adults and older adults in the Brazuca Natal Study. Methods: This is a study of different methodological strategies. 1) The narrative review aimed to verify if surveys could demonstrate an association between serum vitamin E and the occurrence of CVD. Moreover, we would like to understand whether vitamin E deficiency (VED) should also be considered a public health problem. 2) Cross-sectional study, divided into two scientific articles. The first article of this study sought to evaluate the prevalence of VED and cardiovascular risk factors that are associated with serum α-TOH status in adults and elderly people from the Brazuca Natal study. We performed a multiple linear regression analysis between serum α-TOH (dependent variable) and cardiovascular risk factors. The second article aimed to evaluate vitamin E intake, and we would like to identify the principal food sources of this micronutrient intake. To this end, we analyzed socioeconomic and demographic conditions (sex, age, color/race, education, per capita income, and health district of residence), and vitamin E intake (dependent variable). Results: In the narrative review, we observed that VED could be a public health problem. The prevalence of VED varies from 0.6% to 55.5% in the world, with higher percentages in Asia and Europe, where the high mortality rates from CVD stand out. Population studies suggest the protective effects of vitamin E on CVD. However, intervention studies with α-TOH supplementation have not confirmed its cardioprotective action. In article 2 of the crosssectional study, we observed that 24.8% of adults and older adults in Natal had VED, and 89% had low concentrations of circulating α-TOH (below 30 µmol/L). Furthermore, high visceral adiposity index and higher global risk score values were associated with higher serum α-TOH concentrations. Article 3 demonstrated that 95.7% of individuals had a low intake of vitamin E, considering the Estimated Average Requirement (EAR) of 12 mg/day, with lower intake values in individuals over 40 years of age, women, those who have a per capita income of less than the minimum wage and with less education. Soybean oil, açaí pulp, and red meat provided the highest content of ingested vitamin E. Conclusion: From the narrative review, it was demonstrated that VED can be a public health problem. The cross-sectional study observed a high prevalence of VED in the studied population, in which sex, visceral adiposity index and global risk score are associated with serum α-TOH. Furthermore, a low consumption of vitamin E was observed, mainly in older individuals, women and those with low socioeconomic status. Most of the vitamin E consumed came from soybean oil, açaí pulp and red meat, with vitamin E also coming from ultra-processed foods, especially in the lowerincome population (AU).

Vitamin E suppresses aortic ultrastructural alterations induced by toxic doses of monosodium glutamate / La vitamina E suprime las alteraciones ultraestructurales aórticas inducidas por dosis tóxicas de glutamato monosódico

SUMMARY: An association between certain food additives and chronic diseases is reported. Current study determined whether administering toxic doses of the food additive monosodium glutamate (MSG) into rats can induce aortopathy in association with the oxidative stress and inflammatory biomarkers upregulation and whether the effects of MSG overdose can be inhibited by vitamin E. MSG at a dose of (4 mg/kg; orally) that exceeds the average human daily consumption by 1000x was administered daily for 7 days to the rats in the model group. Whereas, rats treated with vitamin E were divided into two groups and given daily doses of MSG plus 100 mg/ kg vitamin E or MSG plus 300 mg/kg vitamin E. On the eighth day, all rats were culled. Using light and electron microscopy examinations, a profound aortic injury in the model group was observed demonstrated by damaged endothelial layer, degenerated smooth muscle cells (SMC) with vacuoles and condensed nuclei, vacuolated cytoplasm, disrupted plasma membrane, interrupted internal elastic lamina, clumped chromatin, and damaged actin and myosin filaments. Vitamin E significantly protected aorta tissue and cells as well as inhibited MSG-induced tissue malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The highest used vitamin E dosage was more effective. Additionally, a significant correlation was observed between the aortic injury degree and tissue MDA, TNF-α, IL-6, and superoxide dismutase (SOD) levels (p=0.001). Vitamin E effectively protects against aortopathy induced by toxic doses of MSG in rats and inhibits oxidative stress and inflammation.

RESUMEN: Se reporta una asociación entre ciertos aditivos alimentarios y enfermedades crónicas. El objetivo de este estudio fue determinar si la administración de dosis tóxicas del aditivo alimentario glutamato monosódico (MSG) en ratas puede inducir aortopatía en asociación con el estrés oxidativo y la regulación positiva de los biomarcadores inflamatorios y si el efecto de una sobredosis de MSG se puede inhibir con vitamina E. Se administró MSG diariamente durante 7 días una dosis de (4 g/kg; por vía oral) que excede el consumo diario humano promedio, en 1000x a las ratas del grupo modelo. Mientras que las ratas tratadas con vitamina E se dividieron en dos grupos y se administraron dosis diarias de MSG más 100 mg/kg de vitamina E o MSG más 300 mg/kg de vitamina E. Todas las ratas fueron sacrificadas en el octavo día. Usando exámenes de microscopía óptica y electrónica, se observó una lesión aórtica profunda en el grupo modelo demostrada por una capa endotelial dañada, células musculares lisas degeneradas (SMC) con vacuolas y núcleos condensados, citoplasma vacuolado, membrana plasmática rota, lámina elástica interna interrumpida, cromatina agrupada y filamentos de actina y miosina dañados. La vitamina E protegió significativamente el tejido y las células de la aorta, además de inhibir el malondialdehído tisular (MDA) inducido por MSG, la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-α). La dosis más alta de vitamina E utilizada fue más efectiva. Además, se observó una correlación significativa entre el grado de lesión aórtica y los niveles tisulares de MDA, TNF-α, IL-6 y superóxido dismutasa (SOD) (p=0,001). La vitamina E efectivamente protege contra la aortopatía inducida por dosis tóxicas de MSG en ratas e inhibe el estrés oxidativo y la inflamación.

Levels of fat-soluble vitamins A, D, and E and their influencing factors in children with obesity / 中国当代儿科杂志

OBJECTIVES@#To investigate the levels of fat-soluble vitamins A, D, and E in children with obesity and their influencing factors.@*METHODS@#A total of 273 children with obesity who attended the Department of Clinical Nutrition, Xi'an Children's Hospital, from January 2019 to April 2021 were enrolled as the obesity group. A total of 226 children with normal body weight who underwent physical examination during the same period were enrolled as the control group. Anthropometric parameters and body composition were measured for both groups, and the serum concentrations of vitamins A, D, and E were also measured.@*RESULTS@#Compared with the control group, the obesity group had significantly higher serum levels of vitamin A [(1.32±0.21) μmol/L vs (1.16±0.21) μmol/L, P<0.001] and vitamin E [(9.3±1.4) mg/L vs (8.3±1.2) mg/L, P<0.001] and a significant reduction in the level of 25-hydroxyvitamin D [(49±22) nmol/L vs (62±24) nmol/L, P<0.001]. In the obesity group, the prevalence rates of marginal vitamin A deficiency, vitamin D deficiency/insufficiency, and vitamin E insufficiency were 5.5% (15/273), 56.8% (155/273), and 4.0% (11/273), respectively. After adjustment for body mass index Z-score and waist-to-height ratio, serum vitamin A level was positively correlated with age (P<0.001), while vitamins E and 25-hydroxyvitamin D levels were negatively correlated with age in children with obesity (P<0.001). After adjustment for age, the serum levels of vitamin A, vitamin E and 25-hydroxyvitamin D were not correlated with degree of obesity, percentage of body fat, and duration of obesity in children with obesity, while the serum levels of vitamins A and E were positively correlated with waist-to-height ratio (P<0.001).@*CONCLUSIONS@#There are higher serum levels of vitamins A and E in children with obesity, especially in those with abdominal obesity, while serum vitamin D nutritional status is poor and worsens with age. Therefore, vitamin D nutritional status should be taken seriously for children with obesity, and vitamin D supplementation should be performed when necessary.

Relationship between micronutrients supplementation during periconceptional period and serum concentration of vitamin E in the 1st trimester of gestational period / 北京大学学报(医学版)

OBJECTIVE@#To explore the association of maternal periconceptional folic acid or multiple micronutrients supplementation during periconceptional period and the serum vitamin E (Vit.E) concentration in the 1st trimester of gestational period.@*METHODS@#A retrospective cohort study was conducted based on the prenatal health care system and clinical laboratory information system. Totally, 22 171 pregnant women who had their prenatal health care and gave birth in Tongzhou Maternal & Child Health Hospital of Beijing from Jan. 2016 to Dec. 2018 were recruited. The usage patterns of nutritional supplements [folic acid (FA) or multiple micronutrients (MM)] during periconceptional period were independent variables, and serum Vit.E concentration and serum Vit.E concentration≥11.2 mg/L in the 1st trimester of gestational period were outcome variables for generalized linear regression model and Logistic regression model, respectively, to analyze the relationships between the independent and outcome variables.@*RESULTS@#The range of the serum Vit.E concentration in the 1st trimester of gestational period was 5.2-24.0 mg/L, and the median concentration was 10.1 (8.8-11.6) mg/L; the excess rate of the serum Vit.E of those who took MM supplementation was 0.3%, and the rates for the groups of FA only or no nutritional supplements used were both 0.1%. Compared with women without nutritional supplement or the women taking FA, the women who took MM had higher serum Vit.E levels in the 1st trimester of gestational period (both P < 0.05). The women taking FA or MM initiated before the conception showed that the serum Vit.E concentration in the 1st trimester of gestational period was higher than that after the conception (P < 0.05), and the serum Vit.E concentration of women who took regularly was higher than that of irregular taking (P < 0.05); with taking compliance elevated, the serum Vit.E concentration of the two groups of women taking FA or MM increased (P < 0.05). The risk of serum Vit.E concentration≥11.2 mg/L among the women taking MM was higher than that of the women without nutritional supplements or taking FA only [odds ratio (OR)=1.36, 95% confidence interval (95%CI): 1.21-1.53; OR=1.39, 95%CI: 1.31-1.48)]; women who took FA or MM showed a lower risk for serum Vit.E concentration≥11.2 mg/L of taking it after the conception than before, the ORs (95%CI) were 0.86 (95%CI: 0.77-0.96) and 0.88 (95%CI: 0.81-0.95), respectively; the women taking the two supplements regularly had higher risk for serum Vit.E concentration≥11.2 mg/L than irregular taking, the ORs (95%CI) were 1.16 (95%CI: 1.05-1.29) and 1.13 (95%CI: 1.04-1.22) for FA and MM users, respectively; with the compliance increasing, the women taking MM had a higher risk of serum Vit.E levels≥11.2 mg/L in the 1st trimester [OR (95%CI) was 1.10 (1.07-1.14)], but for FA users, the OR (95%CI) was 1.04(1.00-1.08).@*CONCLUSION@#Vit.E nutritional status in women in early gestational period in Beijing was generally good, and the excess rate of serum Vit.E was higher in women who took MM during periconceptional period than those without nutritional supplement or taking FA only, suggesting that women need to consider their own Vit.E nutritional status to choose the type of nutritional supplements during periconceptional period, so as to avoid related health hazards.

Endométriose et supplémentation nutritionnelle: une revue de littérature / Endometriosis and nutritional supplementation : a literature review

Contexte et objectif. L'endométriose est une maladie gynécologique caractérisée par la présence des glandes et du stroma endométrial en dehors de la cavité utérine. Elle serait influencée par la nutrition. Cette maladie touche 10 à 15 % des femmes en âge de procréer et a comme composante essentielle l'inflammation chronique. Les symptômes les plus fréquents sont la douleur et l'infertilité. La littérature actuelle fait état des effets bénéfiques des aliments antiinflammatoires et antioxydants sur l'endométriose. L'objectif de la présente mini revue est d'établir des pistes de réflexion sur le bénéfice d'une supplémentation nutritionnelle dans l'endométriose. Méthodes. Nous avons effectué une recherche avec les bases de données de Pubmed, Cinahl, Cochrane Library et Embase pour identifier les articles et essais cliniques randomisés dont sept ont été retenus pour l'analyse. Résultats. La supplémentation en souches probiotiques, en vitamine E et en vitamine C a une influence positive sur les symptômes liés à l'endométriose. De plus, un ensemble des composés contenant des vitamines, sels minéraux, ferments lactiques et oméga 3 et 6 ainsi qu'une alimentation de type anti-inflammatoire et les aliments pauvres en glucides fermentés cibles auraient également une influence positive sur les symptômes. En revanche, la vitamine n'aurait aucun effet significatif. Conclusion. Une prise en charge nutritionnelle, notamment axée sur une supplémentation en antioxydants, anti-inflammatoires et en souches probiotiques constitue une piste prometteuse pour la prise en charge de l'endométriose

Context and objective. Endometriosis is a gynecological disease which is characterized by the presence of endometrial glands and stroma outside the uterine cavity and might be influenced by nutrition. It affects 10 to 15 % of women of childbearing age and has chronic inflammation as an essential component. The most common symptoms are pain and infertility. Current literature reports the beneficial effects of antiinflammatory and antioxidant foods on endometriosis. The present paper reviews the benefits of nutritional supplementation in endometriosis. Methods. A search was performed using the Pubmed, Cinahl, Cochrane Library and Embase database engines to identify articles and randomized clinical trials, of which seven were selected for analysis. Results. Supplementation with probiotic strains, vitamin E and vitamin C has a positive influence on the symptoms associated with endometriosis. In addition, a set of compounds containing vitamins, minerals, lactic ferments and omega 3 and 6 as well as an antiinflammatory type diet and foods low in fermentable carbohydrates would also have a positive influence on the symptoms. In contrast, vitamin D did not have any significant effect. Conclusion. Nutritional management, in particular focusing on supplementation with antioxidants, anti-inflammatory drugs and probiotic strains, is a promising avenue for the management of endometriosis.

Effects of vitamin e on the epithelial-mesenchymal transition in testicular development exposed to valproic acid / Efectos de la vitamina e en la interacción epitelio-mesenquimático en el desarrollo testicular expuesto a ácido valproico

SUMMARY: In testicular differentiation, somatic cells must adopt a specific destiny towards sustentacular, peritubular and interstitial cells, being fundamental for the morphogenesis of seminiferous tubules, mediated by morphogens such as Desert Hedgehog (DHH), insulin-like growth factor-1 (IGF-1) and fibroblastic growth factor 2 (FGF-2). Its alteration could be related to failures in the development mechanisms, such as those caused by valproic acid (VPA), which can be reversed with vitamin E (VE). The objective of the study was to evaluate the epithelial-mesenchymal transition (EMT) in the testicular development of mice exposed to VPA and VE. 12 groups of pregnant female mice were formed that were separated by days post-coital (dpc) at 12.5 dpc, 17.5 dpc and 6 weeks postnatal, each one subdivided into 4 groups of 5 pregnant women each. Subgroups received different treatments from the beginning to the end of gestation orally: 600 mg/kg of VPA, 600 mg/kg of VPA and 200 IU of VE, 200 IU of VE and the control group 0.3 mL of 0.9% physiological solution. Immunohistochemistry was performed for the detection of DHH, IGF-1 and FGF-2. Immunolocalization of DHH was observed in all stages, with more evident significant differences in integrated optical density (IOD) and percentage of immunoreaction area at 6 weeks postnatal, being lower in the VPA group. In IGF-1, lower intensity and distribution of immunostaining was observed in the fetal and pubertal stages in the VPA groups, a similar situation with FGF-2, but only evident at 17.5 dpc, with significant differences. These results demonstrate that VPA can alter EMT between somatic cells in testicular development, with VE being an agent capable of attenuating this process.

RESUMEN: En la diferenciación testicular, es necesario que las células somáticas adopten un destino específico hacia células sustentaculares, peritubulares e intersticiales, siendo fundamental para la morfogénesis de los túbulos seminíferos, mediado por morfógenos como Desert Hedgehog (DHH), Factor de Crecimiento Fibroblástico 2 (FGF-2) y Factor de Crecimiento símil a Insulina (IGF-1). Su alteración se podría relacionar a fallas en los mecanismos de desarrollo, como los que ocasiona el ácido valproico (VPA), los cuales pueden ser revertidos con la vitamina E (VE). El objetivo de estudio fue evaluar la transición epitelio-mesenquimática (EMT) en el desarrollo testicular de ratones expuestos a VPA y VE. Se conformaron 12 grupos de ratones hembra gestantes que se separaron por días post-coital (dpc) a los 12.5 dpc, 17.5 dpc y 6 semanas post-natal, cada uno subdividido en 4 grupos de 5 gestantes cada uno. Cada subgrupo recibió diferentes tratamientos desde el inicio hasta el término de la gestación vía oral: 600 mg/kg de VPA, 600 mg/kg de VPA y 200 UI de VE, 200 UI de VE y el grupo control 0,3 mL de solución fisiológica 0,9%. Se realizó técnica inmunohistoquímica para la detección de DHH, IGF-1 y FGF-2. Se observó la inmunolocalización de DHH en todos los estadios, con diferencias significativas más evidentes en la densidad óptica integrada (IOD) y porcentaje de área de inmunoreacción a las 6 semanas post-natal, siendo menor en el grupo VPA. En IGF-1, se observó en la etapa fetal y puberal menor intensidad y distribución de la marcación en los grupos VPA, situación similar con la inmunomarcación de FGF-2, pero sólo evidenciándose a los 17.5 dpc, con diferencias significativas. Estos resultados demuestran que el VPA puede alterar la EMT entre las células somáticas en el desarrollo testicular, siendo la VE un agente capaz de atenuar este proceso.

Effects of dietary vitamin E on the wound healing induced in Oreochromis niloticus / Efeitos da suplementação com vitamina E na cicatrização de feridas induzidas em Oreochromis niloticus

In the present study, the effect of vitamin E supplementation 450 mg/kg diet was appraised in the process of induced wound healing in Nile tilapias Oreochromis niloticus. Fish were distributed into 18 tanks (10 fish each). Nine tanks were fed the non-supplemented diet and the other 9 tanks were fed 450 mg vitamin E for 60 days. Subsequently, the fish were anesthetized and the epidermis and dermis were surgically removed. The rate of cicatricial retraction and appearance of the wounds, and the histomorphometry of mucous cells, chromatophores, revascularization, inflammatory cells, presence of fibroblasts, collagen fibers, and scales were checked after 3-, 7-, 14-, 21-, and 28-days post-wounding. The retraction rate of the wound was significantly higher in the supplemented fish. The higher concentrations of inflammatory cells, mucous cells, and chromatophores, as well as the production and organization of collagen fibers, resulted in a higher retraction rate. We concluded that a dietary supplementation diet improves specific aspects of the cutaneous healing process in Nile tilapia fish.(AU)

No presente estudo, o efeito da suplementação com vitamina E de 450 mg / kg de dieta foi avaliado no processo de cicatrização induzida de feridas em tilápias do Nilo, Oreochromis niloticus. Os peixes foram distribuídos em 18 tanques (N=10), sendo 9 tanques com dieta não suplementada e os outros 9 tanques suplementados com 450 mg de vitamina E por 60 dias. Posteriormente, os peixes foram anestesiados e a epiderme e derme foram removidas cirurgicamente. Nos tempos pré-determinado de 3, 7, 14, 21 e 28 dias após a ferida foi analisado a taxa de retração cicatricial, a aparência das feridas e a histomorfometria das células mucosas, dos cromatóforos, das células inflamatórias, a revascularização, a presença de fibroblastos, de fibras de colágeno e escamas. A taxa de retração da ferida foi significativamente maior nos peixes suplementados. As maiores concentrações de células inflamatórias, mucosas e cromatóforos, bem como a produção e organização das fibras de colágeno, resultaram em uma maior taxa de retração. Concluímos que a dieta de suplementação melhora aspectos específicos do processo de cicatrização cutânea em peixes de tilápia do Nilo.(AU)

Efeito da adição do ácido palmítico e da vitamina E ao diluidor Tris-gema na criopreservação de sêmen canino / Effect of addition of palmitic acid and Vitamin E to the Tris-egg yolk diluter in canine semen cryopreservation

Canine sperm is a very delicate cell that is quite susceptible to oxidative stress since the cytoplasm is restricted and features little antioxidant reserves. Furthermore, the sperm membrane has some polyunsaturated fatty acids sensitive to lipid peroxidation, which makes it important to addition antioxidant substances to the diluter aiming at decreasing such stress to the sperm cell, particularly during seminal cryopreservation. Several antioxidants have been used in this process in some domestic animal's species, however, the use of palmitic acid has been little reported in works on cryopreservation of semen of the canine species. Hence, this study aimed to assess the effect of addition antioxidants palmitic acid and vitamin E to the Tris-egg yolk diluter on the semen quality of dogs after thawing. Samples were collected from the ejaculates of 4 adult dogs, apparently healthy, of the American Pit Bull Terrier breed of kennels in the city of Teresina, PI, places where the pre-freezing procedures of the dog's semen were performed. The samples were diluted in Tris citric acid fructose (3.28 g Tris-hydroxymethyl-aminomethane, 1.78 g citric acid monohydrate and 1.25 g D-fructose), dissolved in 100 mL distilled water, and added 20% egg yolk and 6% glycerol, at the concentration of 100x106 sptz/mL. The semen samples were divided into 3 mL aliquots to form 3 experimental groups: G1 - Only Tris-egg yolk (Control group); G2 - Tris-egg yolk + 100 µM palmitic acid; and G3 - Tris-egg yolk + 116 µM vitamin E. Semen was collected weekly over a period of little over 2 months. After thawing, thermorresistance test (TTR) was carried out at 0, 30, 60, and 90 min to assess spermatics motility and vigor, in addition to analysis of integrity of plasma membrane, acrosomal membrane and mitochondrial activity of the sperm, using fluorescent probes. These assessments were performed out at the Animal Reproduction Biotechnology Laboratory (LBRA/UFPI). In the TTR, G2 and G3 didn't exhibit significant results for spermatics motility or vigor when compared with the control group. The palmitic acid and vitamin E also had no significant effects on the parameters of acrosomal membrane integrity or mitochondrial activity. However, sperm cryopreserved with the addition of palmitic acid exhibited significant differences for plasma membrane integrity, providing greater protection to the sperm cells in G2. The palmitic acid is one of the most saturated fatty acids in human semen, with reports of great proportions also in the seminal plasma of dogs. Its main role is to protect the plasma membrane from external damage, improving viability and fertility of the sperm after cryopreservation. Data is scarce in the literature on the composition of fatty acids in canine semen and regarding the use of palmitic acid as a seminal antioxidant in that species, which grants further studies aiming to investigate such valuable information for canine reproduction. It is concluded that addition palmitic acid at 100µM concentration to the Tris-egg yolk diluter was able to preserve the integrity of the plasma membrane during the process of cryopreservation of canine semen.(AU)

Vitamin e intake and food sources in adolescent diet: a cross-sectional population-based study / Consumo de vitamina e e fontes alimentares na dieta de adolescentes: um estudo transversal de base populacional

ABSTRACT Objective: To assess vitamin E intake and its relationship with sociodemographic variables, and to identify the main dietary sources of the nutrient in the diet of adolescents. Methods: This is a population-based cross-sectional study that used data from 891 adolescents living in Campinas, SP, participating in ISACamp 2014/15 (Health Survey) and ISACamp-Nutri 2015/16 (Food Consumption and Nutritional Status Survey). The nutrient intake averages were estimated using the Generalized Linear Model, adjusted for the total energy of the diet. Dietary sources of vitamin E were identified from the calculation of the relative contribution. Results: The average vitamin E intake was 3.2 mg for adolescents aged 10 to 13 years and 3.5 mg for those aged 14 to 19 years, results far below the recommended values of 9 and 12 mg, respectively. The prevalence of inadequacy was 92.5%. ­Ten ­foods/­food groups represented 85.7% of vitamin E present in the adolescents' diet; the vegetable oils group accounted for more than a quarter of the contribution (25.5%), followed by cookies (9.1%) and beans (8.9%). Conclusions: There were a low intake and a high prevalence of inadequate vitamin E intake among adolescents in Campinas, with vegetable oil as the main source. For the total number of adolescents, almost 33% of the nutrient content was derived from foods of poor nutritional quality such as cookies, packaged snacks, and margarine. The results of this study can guide public health actions that aim to improve the quality of adolescents' diets.

RESUMO Objetivo: Avaliar a ingestão de vitamina E e sua relação com variáveis sociodemográficas, e identificar as principais fontes alimentares do nutriente na dieta de adolescentes. Métodos: Trata-se de estudo transversal de base populacional que utilizou dados de 891 adolescentes residentes em Campinas, SP, participantes do ISACamp 2014/15 (Inquérito de Saúde) e ISACamp-Nutri 2015/16 (Inquérito de Consumo Alimentar e Estado Nutricional). As médias de ingestão do nutriente foram estimadas por meio de modelo linear generalizado, ajustado pela energia total da dieta. As fontes alimentares de vitamina E foram identificadas pelo cálculo de contribuição relativa. Resultados: A ingestão média de vitamina E foi de 3,2 mg para os adolescentes de 10 a 13 anos e de 3,5 mg para os de 14 a 19 anos, resultados bem inferiores aos valores recomendados de 9 e 12 mg, respectivamente. A prevalência de inadequação foi de 92,5%. Dez alimentos/grupos alimentares representaram 85,7% da vitamina E presente na dieta dos adolescentes; o grupo dos óleos vegetais totalizou mais de um quarto da contribuição (25,5%), seguido dos biscoitos (9,1%) e dos feijões (8,9%). Conclusões: Observou-se baixa ingestão e elevada prevalência de inadequação do consumo de vitamina E nos adolescentes de Campinas, apontando o óleo vegetal como principal fonte. Para o total de adolescentes, quase 33% do teor do nutriente derivava de alimentos de má qualidade nutricional como biscoitos, salgadinhos de pacote e margarina. Os resultados deste estudo podem direcionar ações de saúde pública que objetivem melhorar a qualidade da dieta dos adolescentes.

Vitamin E deficiency and associated factors among Brazilian school children / Deficiência de vitamina E e fatores associados entre crianças escolares brasileiras

ABSTRACT: Objective: Brazilian national data show a significant deficiency in pediatric vitamin E consumption, but there are very few studies evaluating laboratory-proven nutritional deficiency. The present study aimed to settle the prevalence of vitamin E deficiency (VED) and factors associated among school-aged children attended at a primary health unit in Ribeirão Preto (SP). Methods: A cross-sectional study that included 94 children between 6 and 11 years old. All sub-jects were submitted to vitamin E status analysis. To investigate the presence of factors associated with VED, socio-economic and anthropometric evaluation, determination of serum hemoglobin and zinc levels, and parasitological stool exam were performed. The associations were performed using Fisher's exact test. Results: VED (α-tocopherol concentrations <7 µmol/L) was observed in seven subjects (7.4%). None of them had zinc deficiency. Of the total of children, three (3.2%) were malnourished, 12 (12.7%) were anemic, and 11 (13.5%) presented some pathogenic intestinal parasite. These possible risk factors, in addition to maternal-work, maternal educational level, and monthly income, were not associated with VED. Conclusions: The prevalence of VED among school-aged children attended at a primary health unit was low. Zinc deficiency, malnutrition, anemia, pathogenic intestinal parasite, maternal-work, maternal educational level, and monthly income were not a risk factor for VED. (AU)

RESUMO: Objetivo: Determinar a prevalência da deficiência de vitamina E (DVE) e os fatores associados a essa deficiência em escolares atendidos em uma unidade básica de saúde de Ribeirão Preto (SP). Métodos: Estudo transversal que incluiu 94 crianças entre 6 e 11 anos de idade, atendidas em uma unidade básica de saúde. Todos os indivíduos foram submetidos à análise do status de vitamina E. Para investigar a presença de fatores associados à DVE, foi realizada avaliação socio-econômica e antropométrica, determinação dos níveis séricos de hemoglobina e zinco, e exame parasitológico de fezes. As associações foram realizadas por meio do teste exato de Fisher. Resultados: A DVE (concentrações de α-tocoferol <7 µmol/l) foi observada em sete indivíduos (7,4%). Nenhum sujeito apresentou deficiência sérica de zinco. Do total de crianças, três (3,2%) eram desnutridas, 12 (12,7%) anêmicas e 11 (13,5%) apresentavam algum parasita intestinal patogênico. Estes possíveis fatores de risco, além do trabalho materno, escolaridade materna e renda mensal, não foram associados à DVE (p>0,05). Conclusão: A prevalência de DVE em escolares atendidos em uma unidade básica de saúde foi baixa. Desnutrição, anemia, parasitose intestinal, renda mensal e trabalho e nível educacional maternos não se apre-sentaram como fatores de risco para a DVE. (AU)

Daño pulmonar asociado al uso de cigarrillos electrónicos-vapeadores / Pulmonary damage associated with the use of electronic cigarettes or vapers

Ha habido mucha discusión sobre los efectos dañinos para la salud producidos por los cigarrillos electrónicos o vapeadores y su utilidad como ayuda para dejar de fumar. Cada vez aparecen más publicaciones con efectos deletéreos sobre la salud. Esta discusión se ha acentuado en los últimos años, por el importante aumento del uso de los vapeadores en todo el mundo, especialmente entre los adolescentes y adultos jóvenes. En septiembre de 2019 el Centro de Control y Prevención de Enfermedades (CDC) de los EE. UU. alertó sobre un importante número de casos de enfermedad pulmonar asociada al uso de cigarrillo electrónico (EVALI: e-cigarette or vaping associated lung injury). Epidemiológicamente se consideró un brote que al 17 de enero, 2020 ha presentado 2.668 pacientes hospitalizados, con 57 fallecidos. Durante la semana del 15 de septiembre 2019 ocurrió el 'peak' de hospitalizaciones por EVALI. La mayoría eran varones jóvenes. El 82% usó productos con Tetrahidrocanabinoides (THC) y el 14% productos con nicotina. En el lavado bronquio-alveolar de 51 casos de EVALI se encontró la presencia de acetato de Vitamina E, producto utilizado como espesante para la elaboración de productos de 'vapeo' que contienen THC, lo que lo hace un posible factor causal, pero no se puede descartar el papel de otros compuestos tóxicos. Las principales sociedades científicas del mundo y la OMS han advertido de los riesgos a largo plazo del uso de los cigarrillos electrónicos y recomiendan su control y regulación.

There has been a lot of discussion about the harmful health effects caused by electronic cigarettes or vapers and their usefulness as a smoking cessation aid. More and more publications appear with deleterious effects on health. This discussion has been straightened in recent years, due to the significant increase in the use of vapers worldwide, especially among adolescents and young adults. In September 2019, the US Center for Disease Control and Prevention warned of a significant number of cases of lung disease associated with the use of electronic cigarettes (EVALI: e-cigarette or vaping associated lung injury). Epidemiologically it was considered an outbreak that as of January 17, 2020 presented 2668 hospitalized patients, with 57 deaths. During the week of September 15, 2019 the peak of hospitalizations for EVALI occurred. The majority were young men. 82% of them used products with Tetrahydrocanabinoids (THC) and 14% products with nicotine. In the bronchoalveolar lavage of 51 cases of EVALI, the presence of Vitamin E acetate was found, a product used as a thickener for the elaboration of vaping products containing THC, which makes it a possible causal factor, but it cannot be ruled out the contribution of other toxic compounds. The world's leading scientific societies and World Health Organization have warned of the long-term risks of using electronic cigarettes and recommend their control and regulation.

Protective effect of dietary vitamin E (alpha; Tocopherol) on artemisinin induced oxidative liver tissue damage in rats / Efecto protector de la vitamina E en la dieta (alfa; tocoferol) sobre el daño oxidativo del tejido hepático inducido por artemisinina en ratas

This experiment was designed to study the effects of oral administration of artemether which is the most rapid-acting class of antimalarial drugs and the possible protective effect of vitamin E taken with it on the liver of albino rats. A total of twenty-four adult male albino rats were used in this study and were divided into four groups. Group one served as a control and rats in group two exposed to oral intake of artemether daily for fifteen days. The third and fourth groups treated with artemether plus low and high doses of vitamin E respectively. At the end of the experiment, the rats were sacrificed, and the livers were obtained and processed for histological, biochemical and statistical studies. Histological study of the hepatocytes of rats exposed to artemether showed nearly complete disintegration of most cellular contents except few numbers of mitochondria and rough endoplasmic reticulum. Also, the cytoplasm of these cells had few lysosomes, many vacuoles and irregular nuclei with abnormal distribution of chromatin and were shown. The hepatic sinusoids were dilated and filled with blood and vacuoles and bile ductules were abnormal in its structure. Treatment with low and high doses of vitamin E in concomitant with artemether ameliorated the hepatic histopathological lesions and its parenchyma attained nearly normal structure. As far as biochemical changes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in rats treated with artemether were significantly elevated as compared to the control. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were significantly increased in the liver in rats treated with artemether. However, vitamin E ameliorated the rise in ALT and AST with decreased MDA concentration and levels of SOD as compared to the corresponding artemether group values. Results of the present suggest that artemether has a harmful and stressful effect on hepatic tissue and the treatment with vitamin E may alleviate this toxicity.

Este experimento fue diseñado para estudiar los efectos de la administración oral de arteméter, la clase de medicamentos antipalúdicos de acción rápida, y el posible efecto protector de la vitamina E en el hígado de ratas albinas. Se utilizaron un total de 24 ratas albinas machos adultas y se dividieron en cuatro grupos. El grupo uno sirvió como control y las ratas en el grupo dos recibieron la dosis oral de arteméter diariamente durante 15 días. Los grupos tres y cuatro fueron tratados con arteméter, más dosis bajas y altas de vitamina E, respectivamente. Al final del experimento, se sacrificaron las ratas y se obtuvieron y procesaron los hígados para estudios histológicos, bioquímicos y estadísticos. El estudio histológico de los hepatocitos de ratas expuestas a arteméter mostró una desintegración casi completa de la mayoría de los contenidos celulares, excepto algunos mitocondrias y retículo endoplásmico rugoso. Además, el citoplasma de estas células tenía pocos lisosomas, muchas vacuolas y núcleos irregulares con distribución anormal de cromatina. Los sinusoides hepáticos estaban dilatados y llenos de sangre y vacuolas, y los conductos biliares tenían una estructura anormal. El tratamiento con dosis bajas y altas de vitamina E en forma concomitante con arteméter mejoró las lesiones histopatológicas hepáticas y su parénquima alcanzó una estructura casi normal. En cuanto a los cambios bioquímicos, la alanina aminotransferasa (ALT) y la aspartato aminotransferasa (AST) en ratas tratadas con arteméter se elevaron significativamente en comparación con el control. Los niveles de superóxido dismutasa (SOD) y malondialdehído (MDA) aumentaron significativamente en el hígado en ratas tratadas con arteméter. Sin embargo, la vitamina E mejoró el aumento de ALT y AST con una disminución de la concentración de MDA y los niveles de SOD en comparación con los valores correspondientes del grupo de arteméter. Los resultados del presente estudio sugieren que el arteméter tiene un efecto dañino y estresante sobre el tejido hepático y el tratamiento con vitamina E puede aliviar esta toxicidad.

Ameliorative effect of vitamin E on biochemical and ultrastructural changes in artemether-induced renal toxicity in rats / Efecto paliativo de la vitamina E sobre los cambios bioquímicos y ultraestructurales en la toxicidad renal inducida por arteméter en ratas

This experiment was designed to study the administration of normal doses of one of recent antimalarial drug and coadministration of vitamin E on the kidney tissue. A total twenty-four adult male albino rats were used and divided into four groups: the first one served as a control, the second received artemether orally for three days consecutively. The rats of the third and fourth groups received the same dose of artemether concomitantly with 50 and 100 mg/kg vitamin E orally daily for 2 weeks. After the last dose, the rats were sacrificed and the kidney tissues with blood samples obtained and processed for light, electron microscopic and biochemical analysis. Histologically, artemether treated kidneys showed atrophied glomeruli with widened urinary space and kidney tubules were degenerated with disturbed contour and some vacuoles inside it. Ultrastructurally, the glomeruli of this group showed hypertrophic endothelial cells, irregularity of its basement membrane, disrupted foot processes and filtration slits. The kidney tubule cells showed loss of basal infoldings, cytoplasmic vacuolation, polymorphic damaged swollen mitochondria a loss of its microvilli towards its capillary lumen. Artemether plus vitamin E of the rat kidney groups showed improvement of morphological changes compared to the changes seen in artemether alone. These data were confirmed by biochemical findings with marked improvement of blood urea and creatinine levels and increase of anti-oxidant enzyme activities of glutathione peroxidase and superoxide dismutase in the vitamin E treated groups. The results of this study revealed that vitamins E can improve the adverse changes of artemether of rat renal tissue.

Este proyecto fue diseñado para estudiar la administración de dosis normales de uno de los medicamentos antipalúdicos y de la administración de vitamina E en el tejido renal. Se utilizaron 24 ratas albinas machos adultas divididas en cuatro grupos: el primero sirvió como control, el segundo recibió arteméter por vía oral durante tres días consecutivos. Las ratas del tercer y cuarto grupos recibieron la misma dosis de arteméter concomitantemente con 50 y 100 mg / kg de vitamina E por vía oral diariamente durante 2 semanas. Después de la última dosis, las ratas fueron sacrificadas y se obtuvo el tejido renal de cada muestra los cuales fueron procesados para análisis con microscopías de luz y electrónica, además de exámenes bioquímicos. Histológicamente, los riñones tratados con arteméter mostraron atrofia glomerular con espacio urinario ensanchado y túbulos renales degenerados con contorno alterado y algunas vacuolas en su interior. Ultraestructuralmente, los glomérulos de este grupo mostraron células endoteliales hipertróficas, irregularidad de su membrana basal, procesos alterados del pie y hendiduras de filtración. Las células del túbulo renal mostraron pérdida de inflexiones basales, vacuolación citoplasmática, mitocondrias dañadas y pérdida de sus microvellosidades hacia la luz capilar. Arteméter más vitamina E en los grupos de riñón de rata mostraron una mejora de los cambios morfológicos, en comparación con los cambios observados en arteméter solamente. Estos datos fueron confirmados por hallazgos bioquímicos con una marcada mejoría de los niveles de urea y creatinina en sangre y un aumento de las actividades enzimáticas antioxidantes de la glutatión peroxidasa y la superóxido dismutasa en los grupos tratados con vitamina E. Los resultados de este estudio revelaron que la vitamina E puede mejorar los cambios adversos del arteméter del tejido renal de la rata.

Vitamin E reduces radiation injury of hippocampal neurons in mice by inhibiting ferroptosis / 南方医科大学学报

OBJECTIVE@#To explore the protective effect of vitamin E (VE) against radiation injury of hippocampal neurons in mice and explore the possible mechanism.@*METHODS@#Cultured HT-22 and U251 cells with or without exposure to 8 Gy irradiation were treated with VE (200 μmol/L for 24 h), ferroptosis inhibitor (ferrostatin-1, 5 μmol/L for 24 h), apoptosis inhibitor (ZVAD-FMK, 2 μmol/L), or necroptosis inhibitor (100 μmol/L). MTT assay was used to evaluate the cell viability after the treatments, and reduced glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (lipid ROS), and intracellular iron ion levels were detected for assessment of ferroptosis. The mice exposed to 16 Gy irradiation with or without vitamin E (500 U/kg) treatment for 6 weeks were assessed for behavioral changes and cognitive functions using Morris water maze test.@*RESULTS@#Treatment with VE significantly promoted the cell survival following irradiation in HT-22 cells ( < 0.05) but not in U251 cells ( > 0.05). Ferrostatin-1, but not ZVAD or the necroptosis inhibitor, promoted the survival of HT-22 cells following the irradiation. Exposure to irradiation significantly increased ferroptosis-related oxidative stress level in HT-22 cells, manifested by decreased GSH level and increased MDA, lipid ROS and intracellular iron ion levels ( < 0.05); treatment with VE and ferrostatin-1 both obviously reversed radiation-induced ferroptosis-related oxidative stress in the cells ( < 0.05). In Morris water maze test, the mice with radiation exposure showed obviously increased exploration time and distance ( < 0.05), which were significantly decreased after treatment with VE ( < 0.05).@*CONCLUSIONS@#Vitamin E reduces radiation injury by inhibiting ferroptosis in the hippocampal neurons in mice.

Relationship between serum vitamin E concentration in first trimester and the risk of developing hypertension disorders complicating pregnancy / 北京大学学报(医学版)

OBJECTIVE@#To investigate the incidence of hypertension disorders complicating pregnancy (HDCP) and vitamin E (VE) nutritional status among pregnant women in Beijing, and to determine the relationship between serum VE concentration in the first trimester of pregnancy and the risk of developing HDCP.@*METHODS@#A retrospective cohort study was performed including 22 283 cases of pregnant women who underwent singleton deliveries in Tongzhou Maternal & Child Health Hospital of Beijing from January 2016 through December 2018 and received tests of serum VE concentrations in the first trimester of pregnancy. Nonconditional Logistic regression model was used to analyze the association between serum VE concentration levels and the risk of developing HDCP.@*RESULTS@#The total incidence of HDCP was 5.4%, with the incidence of gestational hypertension around 2.1% and the incidence of preeclampsia-eclampsia around 3.3%. The median concentration of serum VE in early pregnancy was 10.1 (8.8-11.6) mg/L, and 99.7% of the participants had normal serum VE concentrations. The incidence of gestational hypertension and that of preeclampsia-eclampsia had been annually increasing in three years; a linear-by-linear association had also been observed between the serum VE concentrations and the years of delivery. According to the results of the univariable and the multivariable Logistic regression analyses, higher risks of developing HDCP had been observed among women with higher serum VE concentrations. Compared to those with serum VE concentrations in interquartile range (P25-P75) of all the participants, the women whose serum VE concentrations above P75 were at higher risks to be attacked by HDCP (OR = 1.34, P < 0.001), gestational hypertension (OR = 1.39, P = 0.002), or preeclampsia-eclampsia (OR = 1.34, P = 0.001), as suggested by the results of the multivariable Logistic regression model analyses. In addition, the women with serum VE concentrations of 11.2 mg/L or above had a significantly higher risk of developing HDCP than those whose serum VE concentrations of P40-P60 of all the participants, and this risk grew higher as serum VE concentrations in the first trimester of pregnancy increased.@*CONCLUSION@#Women in Beijing are at good nutritional status. From January 2016 to December 2018, the incidence of HDCP increased with serum VE concentration level, and serum VE concentration of 11.2 mg/L is an indicator of an increased risk of developing HDCP, suggesting that pregnant women should take nutritional supplements containing VE carefully.