Can pumpkin save us of doxorubicin induced cardiotoxicity? / ¿Puede la calabaza salvarnos de la cardiotoxicidad inducida por doxorrubicina?

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.

A study on the antioxidant activity of rosmarinic acid against carbon tetrachloride-induced liver toxicity in adult male albino rats / Estudio sobre la actividad antioxidante del ácido rosmarínico contra la toxicidad hepática inducida por tetracloruro de carbono en ratas albinas macho adultas

SUMMARY: Carbon tetrachloride (CCl4) is a manufactured chemical and does not occur naturally in the environment. CCl4 is a clear liquid that evaporates very easily. It has a sweet odor. CCl4 is toxic to the mammalian liver and is hepatocarcinogenic in both rats and mice. Rosemary (Rosmarinus Officinalis) is commonly used as a spice and flavoring agent in food processing. It is known for its antioxidant properties. The present study aims to investigate the antioxidant activity of rosmarinic acid (RA) on CCl4-induced liver toxicity in adult male albino rats. Forty adult male albino rats were divided into 4 groups with 10 rats in each group. Group I (control group). Group II animals received RA at a dose of 50 mg/kg/day by oral gavage for 4 weeks. Group III animals received CCl4 intraperitoneally at a dose of 3ml/kg twice weekly for 4 weeks. Group IV animals received CCl4 Plus RA. At the end of the experiment, liver specimens are processed for histological, immunohistochemical, EM and biochemical studies. Administration of RA deceased the elevated serum liver enzymes (AST, ALT, and ALP), elevated MDA level and immunoexpression of the proapoptotic protein (Bax) induced by CCl4. It increased reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also improved the histological and ultrastructural changes induced by CCl4. It appears that Rosmarinic acid has protective effects against CCl4-induced hepatotoxicity as indicated by biochemical, histological, immunohistochemical and ultrastructural results.

RESUMEN: El tetracloruro de carbono (CCl4) es un producto químico fabricado y no se encuentra de forma natural en el medio ambiente. CCl4 es un líquido transparente que se evapora fácilmente; tiene un olor dulce. CCl4 es tóxico para el hígado de los mamíferos y es hepatocarcinogénico tanto en ratas como en ratones. El romero (Rosmarinus officinalis) se usa comúnmente como condimento y agente aromatizante en el procesamiento de alimentos. Es conocido por sus propiedades antioxidantes. El presente estudio tuvo como objetivo investigar la actividad antioxidante del ácido rosmarínico (RA) sobre la toxicidad hepática inducida por CCl4 en ratas albinas macho adultas. Se dividieron cuarenta ratas albinas macho adultas en 4 grupos con 10 ratas en cada grupo. Grupo I (grupo control). Los animales del grupo II recibieron AR a una dosis de 50 mg / kg / día por sonda oral durante 4 semanas. Los animales del grupo III recibieron CCl4 por vía intraperitoneal a una dosis de 3 ml / kg dos veces por semana durante 4 semanas. Los animales del grupo IV recibieron CCl4 Plus RA. Al final del experimento, las muestras de hígado se procesaron para estudios histológicos, inmunohistoquímicos, EM y bioquímicos. La administración de AR eliminó las enzimas hepáticas séricas elevadas (AST, ALT y ALP), el nivel elevado de MDA y la inmunoexpresión de la proteína proapoptótica (Bax) inducida por CCl4. Aumentó el glutatión reducido (GSH), glutatión peroxidasa (GSH-Px), la superóxido dismutasa (SOD) y la inmunoexpresión de la proteína antiapoptótica (Bcl2). También mejoró los cambios histológicos y ultraestructurales inducidos por CCl4. El ácido rosmarínico puede tener efectos protectores contra la hepatotoxicidad inducida por CCl4, tal como lo indican los resultados bioquímicos, histológicos, inmunohistoquímicos y ultraestructurales.

Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients / 中国医学科学院学报

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

Oxidative and biochemical profile of Gyr dairy heifers during the peripartum period / Perfil oxidativo e bioquímico em novilhas Gir leiteiras durante o periparto

O período de transição em vacas leiteiras aumenta o suprimento de oxigênio aos tecidos e a produção de espécies reativas de oxigênio. Junto com o comprometimento do sistema antioxidante, gera estresse oxidativo, que pode estar ligado ao desenvolvimento de diversas doenças. Este estudo teve como objetivo avaliar o estresse oxidativo em 35 novilhas leiteiras Gir, durante o período periparto. Foram analisados ácido úrico, cobre, ferro, zinco, albumina, bilirrubina total, superóxido dismutase (SOD) e glutationa peroxidase (GSH-Px). Um modelo linear com distribuição de Poisson foi aplicado usando o procedimento GENMOD. A primeira medida (30d antes do parto) foi considerada como referência (T0), e as amostras foram coletadas 16 dias antes do parto (T1) e sete (T2), 14 (T3), 28 (T4) e 42 dias pós-parto (T5). Cobre, zinco e albumina variaram dentro da faixa de referência, apesar de ter havido aumento no cobre de 45,92% no T3. Os níveis de ácido úrico aumentaram durante o período de transição, sem diferença significativa até 16 dias pré-parto, quando foi observado aumento de 67,57%, sendo sua maior concentração observada em T4. A SOD teve um aumento maior (300%) do que a GSH-Px (36%) no final do período experimental, acompanhada por adaptações bioquímicas para garantir uma resposta antioxidante eficaz. Dessa forma, pode-se concluir que o período periparto causa estresse oxidativo em novilhas leiteiras Gir.(AU)

O período de transição em vacas leiteiras aumenta o suprimento de oxigênio aos tecidos e a produção de espécies reativas de oxigênio. Junto com o comprometimento do sistema antioxidante, gera estresse oxidativo que pode estar ligado ao desenvolvimento de diversas doenças. Este estudo teve como objetivo avaliar o estresse oxidativo em 35 novilhas leiteiras Gir durante o período periparto. Foram analisados ácido úrico, cobre, ferro, zinco, albumina, bilirrubina total, superóxido dismutase (SOD) e glutationa peroxidase (GSH-Px). Um modelo linear com distribuição de Poisson foi aplicado usando o procedimento GENMOD. A primeira medida (30d antes do parto) foi considerada como referência (T0) e as amostras foram coletadas 16 dias antes do parto (T1) e 7 (T2), 14 (T3), 28 (T4) e 42 dias pós-parto (T5). Cobre, zinco e albumina variaram dentro da faixa de referência, apesar de um aumento no cobre de 45,92% no T3. Os níveis de ácido úrico aumentaram durante o período de transição, sem diferença significativa até 16 dias pré-parto, quando foi observado um aumento de 67,57%, sendo sua maior concentração observada em T4. A SOD teve um aumento maior (300%) do que GSH-Px (36%) no final do período experimental, acompanhada por adaptações bioquímicas para garantir uma resposta antioxidante eficaz. Dessa forma, pode-se concluir que o período periparto causa estresse oxidativo em novilhas leiteiras Gir.(AU)

Remote ischemic conditioning improves rat brain antioxidant defense in a time-dependent mechanism

ABSTRACT Purpose To clarify the best protocol for performing remote ischemic conditioning and to minimize the consequences of ischemia and reperfusion syndrome in brain, the present study aimed to evaluate different time protocols and the relation of the organs and the antioxidant effects of this technique. Methods The rat's left femoral artery was clamped with a microvascular clamp in times that ranged from 1 to 5 minutes, according to the corresponding group. After the cycles of remote ischemic conditioning and a reperfusion of 20 minutes, the brain and the left gastrocnemius were collected. The samples were used to measure glutathione peroxidase, glutathione reductase and catalase levels. Results In the gastrocnemius, the 4-minute protocol increased the catalase concentration compared to the 1-minute protocol, but the latter increased both glutathione peroxidase and glutathione reductase compared to the former. On the other hand, the brain demonstrated higher catalase and glutathione peroxidase in 5-minute group, and the 3-minute group reached higher values of glutathione reductase. Conclusions Remote ischemic conditioning increases brain antioxidant capacity in a time-dependent way, while muscle presents higher protection on 1-minute cycles and tends to decrease its defence with longer cycles of intermittent occlusions of the femoral artery.

Effects of a single trace minerals injection on antioxidant and immune response, resistance to endoparasites, health and growth of newborn Boer kids / Efeitos de uma aplicação de microminerais injetáveis sobre a resposta antioxidante e imunológica, resistência a endoparasitas, saúde e crescimento de cabritos Boer recém-nascidos

This study evaluated the effects of injectable trace minerals (ITM) on antioxidant and immune response, resistance to endoparasites, health and growth of newborn Boer kids. Forty-six Boer kids [24 males and 22 females; 3.94±1.03kg of body weight (BW); 6.2±2.4 d of age] were enrolled in the study. Kids were stratified by type of birth (twins or singlet), sex, and BW and assigned to 1 of 2 treatments: one subcutaneous injection (0.1mL/4.5kg of BW) of (1) saline solution or (2) ITM (60, 10, 5, and 15mg/mL of Zn, Mn, Se and Cu, respectively). Blood samples were collected on d 0, 7, 14, 28 and 56. Feces samples were collected on d 56 and BW on d 0, 28 and 56. Kids were checked daily for signs of diarrhea. ITM kids had greater (P<0.01) plasma concentration of superoxide dismutase and tended (P=0.06) to have greater plasma concentration of glutathione peroxidase. ITM kids had greater (P=0.05) concentration of eosinophils, but no differences (P≥0.11) were observed for other hemogram variables. The ITM application did not affect (P≥0.11) the EPG count. However, ITM kids had less (P=0.02) cumulative incidence of diarhea until d 42 (3.85 vs. 25.93±6.8% for ITM vs. Saline kids, respectively) but no differences (P>0.10) were observed after d 42. The ITM application did not affect (P≥0.40) the growth of kids (0.071 vs. 0.065±0.005kg/day for ITM vs. Saline kids, respectively). Thus, the ITM application, increased the plasma concentration of antioxidant enzymes and eosinophils, decreased the incidence of diarrhea only in the middle of the experiment, but did not affected the EPG count and growth of Boer kids.(AU)

Este estudo avaliou os efeitos de microminerais injetáveis (ITM) na resposta antioxidante e imune, resistência a endoparasitas, saúde e crescimento de cabritos Boer recém-nascidos. Quarenta e seis cabritos [24 fêmeas e 22 machos; 3,94±1,03kg de peso corporal (PC); 6,2±2,4 dias de idade] foram incluídos no estudo. Os animais foram estratificados por tipo de nascimento (gêmeos ou singular), sexo e peso ao nascimento (PN) e atribuídas a 1 de 2 tratamentos. Uma injeção subcutânea (0,1ml/4,5 de PC de (1) Solução salina ou (2) ITM (60,10,5 e 15mg/ml de Zn, Mn, Se e Cu, respectivamente). As amostras de sangue foram coletadas nos dias 0, 7, 14, 28 e 56. As amostras de fezes foram coletadas no dia 56 e PC nos dias 0, 28 e 56. Os recém-nascidos foram verificados diariamente quanto a sinais de diarreia. Os cabritos ITM apresentaram maior (P<0.01) concentração de superóxido desmutase no plasma e tenderam (P=0,06) a ter maior concentração de glutationa peroxidase no plasma. Os animais ITM apresentaram maior (P=0,05) concentração de eosinófilos, mas não foram observadas diferenças (P≥0.11) para outras variáveis do hemograma. A aplicação de ITM não afetou (P≥0.11) a contagem de EPG. No entanto, os cabritos ITM apresentaram menor incidência cumulativa de diarreia (P=0,02) ate d 42 (3,85 vs. 25,93±6,8% para animais ITM vs. animais salina, respectivamente), mas nenhuma diferença (P>0.10) foi observada após d 42. A aplicação do ITM não afetou (P≥0.40) o crescimento dos animais (0.071 vs. 0.065±0.005kg/dia para ITM vs. Salina, respectivamente). Assim, a aplicação do ITM aumentou a concentração plasmática de enzimas antioxidantes e eosinófilos, diminuiu a incidência de diarreia somente na metade do experimento, mas não afetou a contagem de OPG e crescimento de cabritos Boer recém-nascidos.(AU)

Preventive and therapeutic effects and mechanism of Xiaoer Feike Granules on chronic bronchitis induced by lipopolysaccharide in rats / 中国中药杂志

The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1β and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.

Antioxidant activity of selenium on bisphenol-induced apoptosis and testicular toxicity of Albino rats / Actividad antioxidante el selenio sobre la apoptosis inducid por bisfenol y toxicidad testicular en ratas albinas

SUMMARY: Bisphenol A (BPA) is an industrial chemical widely used to make polycarbonate plastics for packaging and epoxy resins. This study sought to examine how selenium (Se) affects BPA toxicity in terms of albino rats' histological structure, antioxidant enzymes and reproductive organs (seminiferous tubules). Twenty-four adult male rats were divided into four experimental groups: Group 1: Control; Group 2: Orally administered BPA; Group 3: Orally administered sodium selenite; Group 4: Treated daily with BPA followed by selenium (Se). All experiment done for 4 weeks. BPA exposure caused changes in the testicular histological structure, which consists apoptosis, and led to changes in several biochemical markers: Malondialdehyde, catalase, superoxide dismutase, and glutathione peroxidase. However, these BPA side effects may be ameliorated in rats treated with BPA-plus-Se. These protective effects of Se may attributable to its ability to remove potentially damaging oxidizing agents in living organisms. The results may confirm that Se countered the oxidant effects and increased the BPA-induced stress response in rats. So, Se promotes the healthy growth and development of mammals by protecting them from oxidative stress. As human are greatly exposed to BPA and it can accumulate in tissues, there is concern about human reproductive functions particularly for occupational workers exposed usually to greater levels of BPA. Thus, the use of BPA in multiple industries must be restricted and the inaccurate usage of plastic containers should be avoided to decrease the health hazards. Administration of Se may protect against the adverse effects of BPA on reproductive functions and structures.

RESUMEN: El bisfenol A (BPA) es un químico industrial ampliamente utilizado para fabricar plásticos de policarbonato para envases y resinas epoxi. Este estudio examinó el efecto de selenio (Se) en la toxicidad del BPA en términos de la estructura histológica, enzimas antioxidantes y los órganos reproductivos (túbulos seminíferos) de ratas albinas. Se dividieron veinticuatro ratas macho adultas en cuatro grupos experimentales: Grupo 1: control; Grupo 2: BPA administrado por vía oral; Grupo 3: BPA administrado por vía oral para; Grupo 4: tratado diariamente con BPA seguido de selenio (Se). El experimento se realizó durante cuatro semanas y se observó que la exposición al BPA provocó cambios en la estructura histológica testicular, incluyendo apoptosis, y alteraciones en varios marcadores bioquímicos:malondialdehído, catalasa, superóxido dismutasa y glutatión peroxidasa. Sin embargo, estos efectos secundarios del BPA pueden mejorar en ratas tratadas con BPA-plus-Se. Estos efectos protectores del Se pueden ser atribuidos a la capacidad de eliminar agentes oxidantes potencialmente dañinos en organismos vivos. Los resultados indicaron que se contrarrestaron los efectos oxidantes y aumentó la respuesta al estrés inducido por BPA en ratas, y favorece el crecimiento y desarrollo en los mamíferos al protegerlos del estrés oxidativo. Debido a la exposición al BPA en el ser humano, se puede acumular en los tejidos, por lo que existe una preocupación por el daño a las funciones reproductivas en particular de los trabajadores que generalmente están expuestos a niveles más altos de BPA. Por lo tanto, se debe restringir el uso de BPA en las industrias y evitar el uso incorrecto de envases de plástico para así disminuir los riesgos para la salud. La administración correcta de Se puede proteger contra los efectos adversos del BPA en las funciones y estructuras reproductivas.

Cardioprotective effect of taurine and ß-alanine against cardiac disease in myocardial ischemia and reperfusion-induced rats

BACKGROUND: The present study analyzed the synergistic protective effect of ß-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. RESULTS: Combined treatment with ß-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of ß-alanine and taurine. ß-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 µM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 µM. CONCLUSION: Taken together, these results suggest that the combined supplementation of ß-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion.

Otoprotection Mechanisms Against Oxidative Stress Caused by Cisplatin

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.

Vitamin C administration attenuated artemether induced hepatic injury in rats / La aAdministración de vitamina C atenúa la lesión hepática inducida por artemeter en ratas

This research was designed to investigate the potential protective effect of vitamin C supplementation against hepatocyte ultrastructural alterations induced by artemether (antimalarial drug) administration. Twenty-four adult male albino rats were used in this study and were divided into four groups (n=6). Group I served as a control and rats in group II administrated artemether (4 mg/kg B.W) orally for three consecutive days. Group III administered artemether plus a low dose of vitamin C (2.86 mg/kg/l water) while group IV received artemether plusa high dose of vitamin C (8.56 mg/kg). At the end of the experimental period (14 days), the harvested liver tissues were examined by transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of liver injury and oxidative stress. Artemether significantly (p<0.05) augmented biomarkers of liver injury such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and oxidative stress such as superoxide dismutase (SOD), Glutathione Peroxidase (GPX), and caused degeneration and damage of the rough endoplasmic reticulum and disrupted mitochondria. The blood sinusoids were also damaged with distortion of their canaliculi. Administration of vitamin C showed improvement of liver biomarkers, and liver parenchyma, especially in a high dose of vitamin C.We concludes that vitamin C is a partial protective agent against artemether-induced liver injury.

Esta investigación fue diseñada para investigar el posible efecto protector de la vitamina C contra las alteraciones ultraestructurales de los hepatocitos, inducidas por la administración de arteméter (medicamento antipalúdico). En el estudio se utilizaron 24 ratas albinas macho adultas y se dividieron en cuatro grupos (n = 6). El grupo I fue designado como control y las ratas en el grupo II se adminstró Arteméter (4 mg / kg de peso corporal) por vía oral durante tres días consecutivos. En el grupo III se administró arteméter, además de una dosis baja de vitamina C (2,86 mg / kg / l de agua) mientras que el grupo IV recibió arteméter más una dosis alta de vitamina C (8,56 mg / kg). Al final del período experimental (14 días), los tejidos hepáticos recolectados se examinaron por microscopía electrónica de transmisión (MET), y las muestras de sangre se analizaron en busca de biomarcadores de daño hepático y estrés oxidativo. El arteméter aumentó significativamente (p <0,05) los biomarcadores de daño hepático como alanina aminotransferasa (ALT), aspartato aminotransferasa (AST) y estrés oxidativo como superóxido dismutasa (SOD), glutatión peroxidasa (GPX) y causó degeneración y daño de la retículo endoplásmico rugoso y mitocondrias alteradas. Los sinusoides sanguíneos también fueron dañados con la distorsión de sus canalículos. La administración de vitamina C mostró una mejoría de los biomarcadores hepáticos y el parénquima hepático, especialmente en una dosis alta de vitamina C. Concluimos que la vitamina C es un agente protector parcial contra la lesión hepática inducida por arteméter.

The effect of rosmarinic acid on deformities occurring in brain tissue by craniectomy method. Histopathological evaluation of IBA-1 and GFAP expressions

Abstract Purpose To investigate the role of Rosmarinic acid (RA) in the prevention of traumatic brain injury and the immunohistochemical analysis of IBA-1 and GFAP expressions. Methods Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows; control group, traumatic brain injury (TBI) group, and TBI+RA group. After traumatic brain injury, blood samples were taken from the animals and analyzed with various biochemical markers. And then IBA-1 and GFAP expressions were evaluated immunohistochemically. Results Significant results were obtained in all biochemical parameters between groups. Immunohistochemical sections showed IBA-1 not only in microglia and macrophage activity but also in degenerative neurons in blood vessel endothelial cells. However, GFAP reaction and post-traumatic rosmarinic acid administration showed positive expression in astrocytes with regular structure around the blood vessel. Conclusion Rosmarinic acid in blood vessel endothelial cells showed that preserving the integrity of astrocytic structure in the blood brain barrier may be an important antioxidant.

Mild-intensity Exercise Triggers VEGF in the Digestive Tract Via Both Hypoxic and Nonhypoxic Mechanisms

Abstract Hypoxia occurs in the splanchnic region during exercise associated with sympathetic activity. In the elderly, vascular insufficiency and low vascular endothelial growth factor (VEGF) expression are observed. Compared to young people, sympathetic signals of older individuals are blunted and more resistant to splanchnic blood flow alterations during exercise. VEGF induces vasodilation responses and hence may retain blood in the splanchnic vascular bed. We hypothesized that regular mild-intensity exercise triggers weak VEGF expression in the digestive tract of the elderly. The effects of exercise on the levels of VEGF, superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in the stomach, jejunum, ileum and colon tissues were evaluated. With exercise, the VEGF levels in the stomach and colon increased. Although the SOD, GPx, and MDA levels decreased in the stomach, they increased in the colon. T-AOC increased in the stomach and there was no change in the jejunum, ileum and colon. The hypoperfusion during exercise was not equal in all regions of the gastrointestinal tract in the aged subjects. Hypoxia and other exercise-related mechanisms could have led to this VEGF induction. The stomach, jejunum, and ileum might have developed resistance to ischemia. The induction of VEGF may be beneficial in aging-associated impaired gastrointestinal homeostasis and neovascularization.

Efeitos da vareniclina no tecido pulmonar em modelo animal / Effects of varenicline on lung tissue in the animal model

RESUMO Objetivo O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental. Métodos Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas. Resultados Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas. Conclusões Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar.

ABSTRACT Objective This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study. Methods A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out. Results Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations. Conclusion This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.

Estudo da morfologia e status oxidativo em rim de ratos com nefropatia isquêmica após tratamento com células-tronco mesenquimais de tecido adiposo / Study of morphology and oxidative status in kidney of rats with ischemic nephropathy after treatment with adipose tissue mesenchymal stem cells

A nefropatia isquêmica é uma doença renal crônica provocada pela redução do fluxo sanguíneo renal que pode progredir para a doença renal terminal, cujo tratamentos disponíveis se baseiam em terapias substitutivas da função renal, como diálise ou transplante renal. No entanto, devido ao alto custo dos tratamentos e a carência de órgãos, se faz necessária a busca por novas terapias, como as células-tronco (CT). Apesar do potencial terapêutico das CT em doenças crônicas, não está claro se essas células mantêm seus efeitos benéficos em órgãos lesionados por tempo prolongado. O objetivo desse estudo foi avaliar os efeitos precoces e tardios do tratamento com células-tronco adiposas (CTA) sobre a morfologia e o status oxidativo em rins de ratos com nefropatia isquêmica. A isquemia renal foi induzida pelo modelo 2rins-1clip (2R1C) e, depois de um mês da clipagem da artéria renal, foram injetadas 106 células-tronco na região subscapsular do rim afetado. Após 15 e 30 dias da injeção das CTA, a morfologia renal foi verificada por meio da análise macroscópica, microscópica e ultraestrutural. Além disso, o status oxidativo foi avaliado no tecido renal através da mensuração da atividade das enzimas antioxidantes catalase e glutationa peroxidase; e de marcadores biológicos de dano oxidativo, como proteínas carboniladas, 3-Nitrotirosina e 4-Hidroxinonenal. Por imunoperoxidase foi possível localizar as células-tronco adiposas GFP+ foram rastreadas e encontradas tanto 15 dias, quanto 30 dias após a injeção na região subcapsular. A restauração da arquitetura renal foi evidenciada 15d após o uso das células, onde detectamos redução na deposição de fibras colágenas no parênquima renal, o que não foi observado 30d após o uso das células. Os resultados também foram confirmados através da análise da ultraestrutura renal que mostraram restauração da arquitetura renal no grupo de 15d, não evidenciada no grupo de 30d. Quanto a análise do status oxidativo, somente os animais com nefropatia isquêmica mais prolongada apresentaram estresse oxidativo com redução da atividade da enzima antioxidante catalase no tecido renal. Além disso, foi observado dano proteico e lipídico, sem melhora dessa condição nos animais 30d após o tratamento com as células-tronco. No modelo de nefropatia isquêmica avaliado, o tratamento com CTA mostrou benefícios na morfologia renal a curto prazo, mas não tardiamente, apesar da permanência dessas células no tecido. Acreditamos que o estresse oxidativo, evidenciado somente no tecido renal com isquemia mais prolongada, possa ter dificultado a ação das células-tronco, contribuindo para tais achados. Esses resultados abrem perspectivas para o aprofundamento do estudo quanto à caracterização dos mecanimos de ação das CTA nas respostas anti-fibrogênicas, assim como o estabelecimento do número, frequência, vias de administração e melhor momento para uso dessas células no tratamento de doenças renais crônicas.

Ischemic nephropathy is a chronic kidney disease caused by reduced kidney blood flow that can progress to end stage kidney disease, whose available treatments are based on kidney function replacement therapies, such as dialysis or kidney transplantation. However, due to the high cost of treatments and the lack of organs, it is necessary to search for new therapies, such as stem cells (SC). Despite the therapeutic potential of SC in chronic diseases, it is unclear whether these cells maintain their beneficial effects on injured organs for a long time. The aim of this study was to evaluate the early and late effects of adipose-derived stem cells (ADSC) treatment on the morphology and oxidative status in kidneys of rats with ischemic nephropathy. Renal ischemia was induced by the 2kidneys-1clip (2K1C) model and, after a month of clipping the renal artery, 106 stem cells were injected into the subscapsular region of the affected kidney. After 15 and 30 days of ADSC injection, renal morphology was verified by macroscopic, microscopic, and ultrastructural analysis. In addition, oxidative status was assessed in renal tissue by measuring the activity of the antioxidant enzymes catalase and glutathione peroxidase; and biological markers of oxidative damage, such as carbonylated proteins, 3-nitrotyrosine and 4-hydroxynonenal. By immunoperoxidase, it was possible to locate GFP + adipose-derived stem cells that were tracked and found both 15 days and 30 days after injection in the subcapsular region. The restoration of the renal architecture was evidenced 15d after the use of the cells, where we detected a reduction in the deposition of collagen fibers in the renal parenchyma, which was not observed 30d after the use of the cells. The results were also confirmed by analyzing the renal ultrastructure, which showed restoration of the renal architecture in the 15d group, not evidenced in the 30d group. Regarding the analysis of oxidative status, only animals with more prolonged ischemic nephropathy presented oxidative stress with reduced activity of the antioxidant enzyme catalase in renal tissue. In addition, protein and lipid damage was observed, with no improvement in this condition in the animals 30d after treatment with stem cells. In the evaluated ischemic nephropathy model, treatment with ADSC showed benefits in renal morphology in the short term, but not late, despite the permanence of these cells in the tissue. We believe that oxidative stress, evidenced only in renal tissue with more prolonged ischemia, may have hindered the action of stem cells, contributing to such findings. These results open perspectives for further study on the characterization of ADSC mechanisms of action in anti-fibrogenic responses, as well as the establishment of the number, frequency, routes of administration and the best time to use these cells in the treatment of chronic kidney diseases.

The association between genetic polymorphism of glutathione peroxidase 1 (rs1050450) and keratoconus in a Turkish population / A associação entre o polimorfismo genético da glutationa-peroxidase 1 (rs1050450) e pacientes com ceratocone em uma população turca

ABSTRACT Purpose: To investigate the potential associations between keratoconus and catalase rs1001179, superoxide dismutase 2 rs4880, and glutathione peroxidase 1 rs1050450 gene polymorphisms in a Turkish population. Methods: The study group included 121 unrelated keratoconus patients and 94 unrelated healthy controls. Blood samples (200 ml) were collected from all patients and controls to isolate genomic DNA. Genotyping was performed to identify rs1001179, rs4880, and rs1050450 using real-time polymerase chain reaction (PCR). Genotype and allele frequencies were calculated; their associations with keratoconus risk were assayed, and the association with keratoconus risk and demographic factors was examined. Results: Glutathione peroxidase 1 rs1050450 polymorphism was present in 41% cases compared with 29% controls (OR=1.66; 95% CI=1.11-2.50; p=0.014). No association was observed between catalase rs1001179 and SOD2 rs4880 polymorphisms and keratoconus (for all, p>0.05). Conclusions: This study evaluated possible relationships between rs1050450, rs1001179, and rs4880 polymorphisms and keratoconus susceptibility. We found a possible association between glutathione peroxidase 1 rs1050450 polymorphism and an increased risk of keratoconus. However, the genotype and allele frequencies were identical in the catalase rs1001179 and superoxide dismutase 2 rs4880 polymorphisms. Further studies are needed to analyze the effect of such variations in identifying keratoconus susceptibility.

RESUMO Objetivo: Investigar as possíveis associações entre o ceratocone e os polimorfismos rs1001179 da catalase, rs4880 da superóxido-dismutase 2 e rs1050450 da glutationa-peroxidase 1 rs1050450 em uma população turca. Métodos: O grupo de estudo incluiu 121 pacientes com ceratocone não relacionados e 94 controles saudáveis também sem pa rentesco. Amostra de sangue (200 mL) foram coletadas de todos os pacientes e controle para isolar o DNA genômico. A genotipagem foi realizada para identificar rs1001179, rs4880 e rs1050450 utilizando a reação em cadeia da polimerase (PCR) em tempo real. As frequências de genótipos e alelos foram calculadas, suas associações com o risco de ceratocone foram avaliadas, e a associação com risco de ceratocone e fatores demográficos foi examinada. Resultados: O polimorfismo da glutationa-peroxidase 1 rs1050450 estava presente em 41% dos casos, comparado com 29% dos controles (OR=1,66, IC 95%=1,11-2,50; p=0,014). Não foi observada associação entre o ceratocone e os polimorfismos rs1001179 e SOD2 rs4880 da catalase (para todos, p>0,05). Conclusões: Este estudo avaliou possíveis relações entre os polimorfismos rs1001179, rs4880 e suscetibilidade a cerato cone. Encontramos uma possível associação entre po limorfis mo da glutationa-peroxidase 1 rs1050450 e um risco aumentado de ceratocone. No entanto, o genótipo e as frequências alélicas foram idênticas nos polimorfismos rs1001179 da catalase e superóxido-dismutase 2 rs4880. Mais estudos são necessários para esclarecer o efeito dessas va riações na detecção da sus cetibilidade ao ceratocone.

Effect of Arrabidaea chica extract against chemically induced breast cancer in animal model

Abstract Purpose: To examine the effects of Arrabidaa chica (Bignoniacea) extract, a native plant of the Amazon known as crajiru, on a 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced breast cancer model in Wistar rats. Methods: We compared the response of breast cancer to the oral administration of A. chica extract (ACE) for 16 weeks, associated or not with vincristine. Groups: normal control; DMBA (50mg/kg v.o,) without treatment; DMBA+ACE (300 mg/kg); DMBA+vincristine. 500μg/kg injected i.p; DMBA+ACE+Vincristine 250μg/kg i.p. Imaging by microPET and fluorescence, biochemistry, oxidative stress, hematology and histopathology were used to validate the treatments. Results: All animals survived. A gradual weight gain in all groups was observed, with no significant difference (p>0.05). The oral administration of ACE and ACE+vincristine 50% significantly reduced breast tumors incidence examined with PET-18FDG and fluorescence (p<0.001). Significant reduction of serum transaminases, oxidative stress and hematological toxicity were observed in these groups. Antioxidant enzyme levels in breast tissue were significantly higher compared to the DMBA and DMBA+vincristine groups. Conclusion: These results demonstrate for the first time that ACE positively influences the treatment of DMBA-induced breast cancer in animal model, inducing a reduction in oxidative stress and chemotherapy toxicity, meaning that ACE may have clinical implication in further studies.

Relationship of the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) index with antioxidant enzymes and with the oxLDL/HDL index

Introduction: The low-density lipoprotein (LDL)/high-density lipoprotein (HDL) index is a predictive factor for atherosclerosis, which is associated with oxidative modifications. Objective: To assess the association of the index with oxidative stress markers. Methods: 444 subjects were included and were clinically, anthropometrically and biochemically characterized; superoxide dismutase, glutathione peroxidase 3 (GPx3), magnesium and oxidized LDL (oxLDL) index (oxLDL/HDL) were quantified. Results: A decrease of 1.014 units in the LDL/HDL index was associated with a superoxide dismutase increase of 1 unit/mL (p = 0.030), while a decrease of 0.023 units was associated with a GPx3 increase of 1 nmol/min/mL (p < 0.0005). An increase of one unit in the index was associated with an increase of 0.831 in the oxLDL/HDL index (p < 0.05). After controlling for the effect of gender, age, smoking, obesity and insulin resistance, a reduction of 0.001 per index unit was associated with an increase of 1 µg/g of magnesium in the nails (p = 0.020). Conclusions: The LDL/HDL index shows an inverse relationship with the antioxidant status and a direct relationship with oxidation status, regardless of other cardiovascular and oxidative stress risk factors.

Marcadores de estrés oxidativo en pacientes con esclerosis múltiple durante un brote y su remisión / Oxidative stress markers in patients with multiple sclerosis during an outbreak and its remission / Marcadores de estresse oxidativo em pacientes com esclerose múltipla durante um surto e sua remissão

La esclerosis múltiple remitente-recurrente (EM-RR) es una enfermedad desmielinizante del sistema nervioso central. A fin de entender la asociación del estrés oxidativo a nivel periférico con la recaída de la enfermedad se determinaron los niveles de marcadores de estrés oxidativo en plasma de pacientes en la recaída o brote y una semana después de la misma. Se analizaron muestras de 60 personas (20 pacientes con recaída, 20 pacientes sin recaída y 20 controles sanos). Se cuantificaron mediante métodos espectrofotométricos las actividades enzimáticas de óxido nítrico sintasa (ONS), glutatión peroxidasa (GPx), los niveles de lipoperóxidos y nitritos-nitratos y la fluidez de membrana. En el brote de la enfermedad aumentan significativamente los niveles de las actividades enzimáticas de ONS y GPx y los niveles de nitritos-nitratos y lipoperóxidos (p<0,01 en todos los casos), al ser comparados con los de individuos sanos. Dichos parámetros disminuyeron significativamente una semana después de iniciado el brote. Además, los parámetros evaluados se mantuvieron elevados en pacientes que no experimentaron un brote de la enfermedad cuando se los comparó con individuos sanos. La fluidez de membrana en los pacientes con y sin brote fue similar a la de los controles. En conclusión, el estrés oxidativo es un componente importante en los pacientes con esclerosis múltiple.

Recurrent-remitting multiple sclerosis (RR-MS) is a demyelinating disease of the central nervous system. In order to understand the association of oxidative stress at the peripheral level with the relapse of the disease, the levels of oxidative stress markers in plasma of patients in the relapse or outbreak and one week after relapse were determined. Samples of 60 subjects were analyzed (20 patients in relapse, 20 patients without relapse, and 20 healthy controls). The enzymatic activities of nitric oxide synthase (NOS), glutathione peroxidase (GPx), lipoperoxides and nitrite-nitrate levels and membrane fluidity were quantified by spectrophotometric methods. In relapse, the levels of enzymatic activities of NOS and GPx, and the levels of lipoperoxides and nitrites-nitrates were significantly increased (p<0.01, in all cases), compared with healthy individuals. These parameters decreased significantly 1 week after the start of the outbreak. In addition, the parameters evaluated remained high in patients who did not experience an outbreak of the disease compared to healthy subjects. The membrane fluidity in the patients with and without outbreak was similar to that of the controls. In conclusion, oxidative stress is an important component in patients with multiple sclerosis.

A esclerose múltipla recorrente-remitente (EM-RR) é uma doença desmielinizante do sistema nervoso central. Para compreender a associação do estresse oxidativo a nível periférico com a recaída da doença foram determinados os níveis de marcadores de estresse oxidativo em plasma de doentes na recaída ou surto e uma semana após a recaída. Foram analisadas a amostras de 60 pessoas (20 pacientes com recaída, 20 pacientes sem recaída e 20 controles saudáveis). As atividades enzimáticas de óxido nítrico sintase (ONS), glutationa peroxidase (GPX), os níveis de lipoperóxidos e nitritos-nitratos e a fluidez de membrana foram quantificadas por métodos espectrofotométricos. No surto da doença aumentam em forma significativa os níveis da atividade enzimática de ONS e GPX, e os níveis de nitritos-nitratos e lipoperóxidos (p<0,01 em todos os casos), em comparação com os indivíduos saudáveis. Esses parâmetros diminuíram significativamente uma semana após o início do surto. Além disso, os parâmetros avaliados permaneceram elevados em pacientes que não experimentaram um surto da doença quando comparados com indivíduos saudáveis. A fluência de membrana nos pacientes com e sem surto foi semelhante à dos controles. Em conclusão, o estresse oxidativo é um componente importante nos pacientes com esclerose múltipla.

The Effects of Trimetazidine on QT-interval Prolongation and Cardiac Hypertrophy in Diabetic Rats / Os Efeitos da Trimetazidina no Prolongamento do Intervalo QT e na Hipertrofia Cardíaca em Ratos Diabéticos

Abstract Background: Trimetazidine (TMZ) is an anti-ischemic drug. In spite of its protective effects on cardiovascular system, there is no scientific study on the usefulness of TMZ treatment for prolonged QT interval and cardiac hypertrophy induced by diabetes. Objectives: To evaluate the effects of TMZ on QT interval prolongation and cardiac hypertrophy in the diabetic rats. Methods: Twenty-four male Sprague-Dawley rats (200-250 g) were randomly assigned into three groups (n = 8) by simple random sampling method. Control (C), diabetic (D), and diabetic administrated with TMZ at 10 mg/kg (T10). TMZ was administrated for 8 weeks. The echocardiogram was recorded before isolating the hearts and transfer to a Langendorff apparatus. Hemodynamic parameters, QT and corrected QT interval (QTc) intervals, heart rate and antioxidant enzymes were measured. The hypertrophy index was calculated. The results were evaluated by one-way ANOVA and paired t-test using SPSS (version 16) and p < 0.05 was regarded as significant. Results: The diabetic rats significantly indicated increased hypertrophy, QT and QTc intervals and decreased Left ventricular systolic pressure (LVSP), Left ventricular developed pressure (LVDP), rate pressure product (RPP), Max dp/dt, and min dp/dt (±dp/dt max), heart rate, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in the heart. Treatment with TMZ in the diabetic animals was significantly improved these parameters in comparison to the untreated diabetic group. Conclusions: TMZ improves QTc interval prolongation and cardiac hypertrophy in diabetes.

Resumo Fundamento: A trimetazidina (TMZ) é uma droga anti-isquêmica. Apesar de seus efeitos protetores sobre o sistema cardiovascular, não há estudos científicos sobre a utilidade do tratamento com TMZ para o intervalo QT prolongado e a hipertrofia cardíaca induzida pelo diabetes. Objetivo: Avaliar os efeitos da TMZ no prolongamento do intervalo QT e na hipertrofia cardíaca em ratos diabéticos. Métodos: Vinte e quatro ratos machos Sprague-Dawley (200-250 g) foram distribuídos aleatoriamente em três grupos (n = 8) pelo método de amostragem aleatória simples. Controle (C), diabético (D) e diabético administrado com TMZ a 10 mg/kg (T10). A TMZ foi administrada por 8 semanas. O ecocardiograma foi registrado antes de isolar os corações e transferir para um aparelho de Langendorff. Foram medidos os parâmetros hemodinâmicos, intervalo QT e intervalo QT corrigido (QTc), frequência cardíaca e enzimas antioxidantes. O índice de hipertrofia foi calculado. Os resultados foram avaliados pelo one-way ANOVA e pelo teste t pareado pelo SPSS (versão 16) e p < 0,05 foi considerado significativo. Resultados: Os ratos diabéticos indicaram hipertrofia aumentada, intervalos QT e QTc e diminuição da pressão sistólica no ventrículo esquerdo (PSVE), pressão desenvolvida no ventrículo esquerdo (PDVE), duplo produto (DP), Max dp/dt e min dp/dt (± dp/dt max), frequência cardíaca, superóxido dismutase (SOD), glutationa peroxidase (GPx) e catalase no coração. O tratamento com TMZ nos animais diabéticos melhorou significativamente esses parâmetros em comparação com o grupo diabético não tratado. Conclusões: A TMZ melhora o prolongamento do intervalo QTc e a hipertrofia cardíaca no diabetes.