RESUMO
Chloroxine (5,7-dichloro-8-hydroxyquinoline) is a molecule utilized in some shampoos for the therapy of seborrheic dermatitis of the scalp and dandruff. In this study, we investigated the inhibition effects of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate compounds on the 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA Reductase) and urease enzymes. We have obtained results for the HMG-CoA Reductase and urease enzymes at the micromolar level. In our study, inhibition result of 5,7-dichloro-8-hydroxyquinoline and Methyl 3,4,5-trihydroxybenzoate on HMG-CoA reductase showed lower values 2.28 ± 0.78 and 33.25 ± 5.04 µg/ml, respectively. Additionally, inhibition result of 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate on urease showed lower values 6.18 ± 1.38 and 8.51 ± 1.35 µg/ml, respectively. Molecular docking calculations were made for their biological activities were compared. In the present work, the structures of the related compounds (1 and 2) were drawn using Gaussian 09 software and done geometry optimization at DFT/B3LYP/6-31G* basis set with aforementioned program. Cytotoxicity potential of these compounds against human lung cancer demonstrated that these compounds had good cytotoxic effects. Both compounds significantly decreased lung cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in lung cell viability. In general, we can say that of the two tested compounds, 5,7-dichloro-8-hydroxyquinoline and methyl 3,4,5-trihydroxybenzoate have cytotoxic effects in all cell types, and this effect is particularly strong in lung cells. Activities were performed at concentrations of 10, 20, 50, 70, and 100 µl and we achieved good results. Lung cell viability (%) value was better at 100 µl concentration and IC50 of them were 54.28 and 48.05 µM.
Assuntos
Antineoplásicos , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Humanos , Simulação de Acoplamento Molecular , Urease , Hidroximetilglutaril-CoA Redutases/metabolismo , Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Oxiquinolina , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologiaRESUMO
Food consumption involves several dimensions, being some of them directly associated with the consumers' characteristics. The interrelationships between these domains impact consumer behaviour for food choice and the consequent decisions for food consumption. In these frameworks, economic motivations are determinant. On the other hand, the scientific literature highlights that the economic-based stimuli to choose food is still underexplored. In this perspective, the objective of this study was to assess the main sociodemographic and anthropometric determinants of the economic motivations for food choice. For that, a questionnaire survey was carried out involving 11,919 respondents from 16 countries. A validated questionnaire was used, translated into the native languages in all participating countries, using a back-translation process. First, the information obtained was assessed through factor analysis to reduce the number of variables associated with the economic motivations and to identify indexes. After, and considering the indexes obtained as dependent variables, a classification and regression tree analysis was performed. As main insights, it is highlighted that the main determinants of the economic motivations are country of residence, age, gender, civil state, professional activity, educational level, living environment, responsibility for buying food, weight, height, body mass index, healthy diets and physical exercise practices. Additionally, the results also reveal that economic motivations may be associated with two indexes, one related to convenience attitudes and the other to quality concerns. Finally, the younger persons and the women are the social groups more concerned with healthy diets and food quality. In conclusion, this work confirmed that food choice is to a high extent influenced by several sociodemographic and behavioural factors.
Assuntos
Comportamento do Consumidor , Motivação , Comportamento de Escolha , Dieta Saudável , Feminino , Preferências Alimentares , HumanosRESUMO
This study aimed at investigating the influence of some sociodemographic factors on the eating motivations. A longitudinal study was carried conducted with 11960 participants from 16 countries. Data analysis included t-test for independent samples or ANOVA, and neural network models were also created, to relate the input and output variables. Results showed that factors like age, marital status, country, living environment, level of education or professional area significantly influenced all of the studied types of eating motivations. Neural networks modelling indicated variability in the food choices, but identifying some trends, for example the strongest positive factor determining health motivations was age, while for emotional motivations was living environment, and for economic and availability motivations was gender. On the other hand, country revealed a high positive influence for the social and cultural as well as for environmental and political and also for marketing and commercial motivations.
Assuntos
Dieta/psicologia , Emoções , Preferências Alimentares/psicologia , Comportamentos Relacionados com a Saúde , Motivação , Adolescente , Adulto , Fatores Etários , Idoso , Meio Ambiente , Etnicidade , Feminino , Humanos , Masculino , Marketing , Pessoa de Meia-Idade , Redes Neurais de Computação , Fatores Sexuais , Meio Social , Fatores Socioeconômicos , Adulto JovemRESUMO
The objective of this work was to study the degree of knowledge about dietary fibre (DF), as influenced by factors such as gender, level of education, living environment or country. For this, a descriptive cross-sectional study was undertaken on a non-probabilistic sample of 6010 participants from 10 countries in different continents (Europe, Africa and America). The results showed that the participants revealed on average a positive but still low global level of knowledge, which alerts for the need to take some actions to further inform the population about DF and its role as a component of a healthy diet. The results also indicated differences between genders, levels of education, living environments and countries. The highest level of knowledge was revealed by the participants from female gender, with higher education and living in urban areas. Concerning the country, the best informed were the participants from Romania, followed by those from Portugal and Turkey while the least informed were from Egypt.
Assuntos
Dieta , Fibras na Dieta , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , África , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Fatores Socioeconômicos , Inquéritos e Questionários , Estados Unidos , Adulto JovemRESUMO
Carbamazepine use is the first choice of antiepileptic drugs among epileptic pregnant females. There are many inconclusive studies regard the safety of carbamazepine use during pregnancy. This study aims to investigate the morphological and histopathological teratogenic effects of carbamazepine use during pregnancy. The healthy pregnant females mice divided into equal five groups (each n=20). The first (control) group received distilled water/day. Second, third, fourth and fifth group received 8.75, 22.75, 52.5, 65 mg of carbamazepine/day respectively. Carbamazepine and water were given by gastric gavage throughout gestational period. Fetuses were delivered on the 18th day of gestation by hysterectomy. Fetal measurements and appearance were assessed with investigation the histopathological changes of brain and spinal cord. There was a significant decrease of weight, different organs weight, length, upper and lower limb length of mice in the first day of delivery in fifth group. There was a significant increase of weight, different organs weight, length, upper and lower limb length in the third group. Many congenital anomalies such as spina bifida, meromelia, microphalmia, oligodactyly, anencephaly, neurodegeneration of brain and spinal cord were noticedin fifth group. Teratogenic effect of carbamazepine represented as growth retardation and neurodevelopmental toxicity depending on its overdose degree.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/toxicidade , Carbamazepina/toxicidade , Feto/efeitos dos fármacos , Teratogênicos/toxicidade , Anormalidades Induzidas por Medicamentos/patologia , Animais , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Retardo do Crescimento Fetal/patologia , Peso Fetal/efeitos dos fármacos , Feto/anormalidades , Membro Anterior/anormalidades , Membro Anterior/efeitos dos fármacos , Idade Gestacional , Membro Posterior/anormalidades , Membro Posterior/efeitos dos fármacos , Camundongos , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/patologia , Malformações do Sistema Nervoso/induzido quimicamente , Malformações do Sistema Nervoso/patologia , Gravidez , Medição de RiscoRESUMO
Humans are frequently exposed to aluminum from various food additives, therapeutic treatments and the environment, and it can be potentially toxic. This study is aimed to elucidate the protective effects of propolis against aluminum chloride (AlCl3 )-induced histopathological and immunohistochemical changes in kidney tissues of rats. Sixty Wistar Albino male rats (average weight 250-300 g) were divided into three equal groups. The first served as a negative control. The second received AlCl3 (34 mg/kg bw, 1/ 25 LD 50). The third were administered AlCl3 (34 mg/kg bw, 1/ 25 LD 50) plus propolis (50 mg/kg bw). Doses were given once daily via a gavage for 8 weeks every day. The results showed that shrunken glomeruli, intraglomerular congestion, loss of apical microvilli, degeneration of mitochondria and widened rough endoplasmic reticulum were also observed in the Proximal Convoluted Tubules of these animals. Treatment with propolis ameliorated the harmful effects of AlCl3 ; this was also proved histopathologically by the noticeable improvement in the renal tissues. There were also significant variations in the expressed of ki-67 and p53 proteins. It can be concluded that propolis may be promising as a natural therapeutic agent in AlCl3 -induced renal toxicity and oxidative stress in rat kidneys.
Assuntos
Compostos de Alumínio/antagonistas & inibidores , Cloretos/antagonistas & inibidores , Rim/efeitos dos fármacos , Própole/administração & dosagem , Cloreto de Alumínio , Compostos de Alumínio/toxicidade , Animais , Cloretos/toxicidade , Relação Dose-Resposta a Droga , Humanos , Rim/ultraestrutura , Masculino , Microscopia Eletrônica de Transmissão , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
This study utilized network pharmacology and docking analyses to explore a groundbreaking therapeutic approach for managing the neuropathic pain and depressive disorder (NP/DD) comorbidity. Schisandra chinensis (SC), a common Chinese medicine, has demonstrated numerous beneficial effects in treating neuropsychological disorders. The main objective of this study was to identify potential bioactive components of SC and investigate their interactions with relevant target genes associated with NP/DD. To gain insights into the underlying molecular mechanisms, GO and KEGG analyses were conducted. Furthermore, molecular docking analysis was employed to validate the therapeutic relevance of SC's active ingredients. Seven bioactive components of SC, namely Longikaurin A, Deoxyharringtonine, Angeloylgomisin O, Schisandrin B, Gomisin A, Gomisin G, and Gomisin R, exhibited effectiveness in the treatment of NP/DD. From this list, the first five components were selected for further analysis. The analyses revealed a complex network of interactions between the targets of SC and NP/DD, providing valuable information about the molecular mechanisms involved in the treatment of NP/DD with SC. SC components demonstrated the ability to regulate pathways involving tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), and other growth hormones (GH). Overall, this study contributes to our understanding of the molecular mechanisms underlying the effects of SC in treating NP/DD. Further investigation is necessary to explore the therapeutic potential of SC as a viable strategy for NP/DD comorbidity. These findings lay a solid foundation for future research endeavors in this field, holding potential implications for the development of novel therapeutic interventions targeting NP/DD.
RESUMO
The present study was designed to estimate the effect of aqueous extract of licorice on metiram toxicity in mice. Treating mice with metiram at a dose level of [1/2] LD(50) daily for 3 weeks induced many histological changes in the kidney cortex. The renal tubules lost their characteristic appearance and their lining epithelial cells were degenerated. The glomeruli were atrophied and the renal blood vessels were congested. The intertubular spaces infiltrated by inflammatory leukocytic cells. Metiram caused an increase in proliferating cell nuclear antigen (PCNA) expression in nuclei of tubular epithelial cells. Metiram also caused marked elevation in serum creatinine and blood urea nitrogen. Treating animals with metiram and licorice aqueous extract led to an improvement, in both biochemical and histopathological alterations. These results proved that licorice had an ameliorative effect against kidney injury induced by metiram and this effect may be attributed to its antioxidant activity.
Assuntos
Antioxidantes/farmacologia , Ditiocarb/toxicidade , Fungicidas Industriais/toxicidade , Glycyrrhiza/química , Extratos Vegetais/farmacologia , Insuficiência Renal/tratamento farmacológico , Animais , Antioxidantes/uso terapêutico , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Camundongos , Fitoterapia , Extratos Vegetais/uso terapêutico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/patologiaRESUMO
This study aimed to examine the effects of luteolin (LUT) on chronic neuropathic pain (NP)-induced mood disorders (i.e., anxiety and depression) by regulating oxidative stress, neurotrophic factors (NFs), and neuroinflammation. Chronic constrictive injury (CCI) was used to induce NP in the animals. Animals in the treatment groups received LUT in three doses of 10, 25, and 50 mg/kg for 21 days. The severity of pain and mood disorders were examined. Finally, animals were sacrificed, and their brain tissue was used for molecular and histopathological studies. CCI led to cold allodynia and thermal hyperalgesia. Mood alterations were proven in the CCI group, according to the behavioral tests. Levels of glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), B-cell lymphoma-2 (Bcl2), superoxide dismutase (SOD), catalase (CAT), and nuclear factor erythroid-2-related factor 2 (Nrf2) were reduced in the hippocampus (HPC) and prefrontal cortex (PFC). Furthermore, the levels of MDA, Bcl-2-associated X protein (Bax), and inflammatory markers, including nuclear factor kappa B (NF-κB), NLR family pyrin domain containing 3 (NLRP3), interleukin-1ß (IL-1ß), IL-18, IL-6, and tumor necrosis factor-α (TNF-α) significantly increased in the HPC and PFC following CCI induction. LUT treatment reversed the behavioral alterations via regulation of oxidative stress, neurotrophines, and inflammatory mediators in the HPC and PFC. Findings confirmed the potency of LUT in the improvement of chronic pain-induced anxiety- and depressive-like symptoms, probably through antioxidant, anti-inflammatory, and neuroprotective properties in the HPC and PFC.
Assuntos
Ansiolíticos , Neuralgia , Ratos , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Luteolina/farmacologia , Luteolina/uso terapêutico , Fatores de Crescimento Neural/metabolismo , Constrição , Antidepressivos/uso terapêutico , Estresse Oxidativo , NF-kappa B/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Neuralgia/tratamento farmacológico , Neuralgia/patologiaRESUMO
Introduction: One of the plants that has long been considered by humans is Equisetum arvense L. Equisetum arvense L is now recommended for external use to heal wounds and for internal use to relieve urinary tract and prostate disorders. In the current study, the antioxidant, cytotoxicity, and anti-human lung cancer properties of Equisetum arvense were investigated in in vitro conditions. Material and methods: Total phenolic content, total flavonoid content, radical scavenging activity, and ferrous ion chelating were assessed to evaluate the antioxidant activity. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was chosen to investigate anticancer activity of the plant extract. Results: The plant extract scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) as a free radical with an IC50 of 12.3 ±0.7 µg/ml better than positive controls. The plant was also rich in phenolic compounds with an amount of 396.2 ±3.2 mg GAE/g for total phenolic content. In the MTT assay, human colorectal carcinoma (HCT-8 [HRT-18], Ramos.2G6.4C10, HT-29, and HCT 116) and normal cell lines (HUVEC) were used to study the cytotoxicity and anticancer potential of Equisetum arvense L against human colorectal cancer. Conclusions: The cell viability of Equisetum arvense L was very low against human colorectal carcinoma cell lines without any cytotoxicity towards the normal (HUVEC) cell line. The best anti-human colorectal carcinoma properties of Equisetum arvense L against the above cell lines were observed in the case of the HT 29 cell line.
RESUMO
Misuse and abuse of anabolic androgenic steroids (AAS) such as oxymetholone (OM) cause side effects such as male infertility, cardiovascular disorders, musculoskeletal, and hepato-renal dysfunctions in athletes. The aim of this study was to evaluate the protective effects of Lepidium draba L. (L. draba) extract on OM-induced hepato-renal toxicity. Thirty adult male Wistar rats into six groups (n = 5) were randomly divided as follows: control (normal saline), OM (5 mg/kg/day), L. draba-treated (100, 200, and 400 mg/kg/d) plus 5 mg/kg/day OM, and L. draba (400 mg/kg/d) groups. Normal saline, OM and L. draba extract were orally administered for 30 days. On day 31 of the study, hepatic and renal biochemical parameters were measured. Serum cytokines (IL-1ß, IL-10, IL-6) tumor necrosis factor- α (TNF-α) and nitric oxide, levels alongside catalase, glutathione peroxidase, and superoxide dismutase activity were evaluated. Also, changes in liver and kidney histopathology were evaluated. Finally, the anti-oxidant properties of the extract were determined. The results of this study showed that in the groups treated with the L. draba extract, hepatic-renal biochemical parameters improved and also the level of nitric oxide and inflammatory cytokines decreased and the activity of anti-oxidant enzymes increased compared with the OM group. These findings revealed that L. draba, due to its high anti-oxidant properties and high content of polyphenols (especially flavonoids), can improve OM-induced hepato-renal oxidative damages. PRACTICAL APPLICATIONS: L. draba due to its remarkable anti-oxidant and anti-inflammatory properties can protects the kidney and liver injuries against oxymetholone. These features are attributed to the presence of phenolic and flavonoid components. This fidings would be helpful to desgin new therapeutic agents for treating and preventing liver/kidney injuries.
Assuntos
Lepidium , Oximetolona , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Lepidium/metabolismo , Masculino , Óxido Nítrico , Estresse Oxidativo , Oximetolona/farmacologia , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Solução Salina/farmacologiaRESUMO
Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease caused by a malfunction of the immune system. The aim of this study was to examine the anti-arthritic effects and suggest the mechanisms of actions of diosmin and trolox in male Wistar rats. Complete Freund's adjuvant (CFA) was used to establish RA in the animals by subcutaneous injection of 100 µL CFA/rat into plantar region of right hind leg in two consecutive days. Diosmin and/or trolox were administered orally at a dosage of 20 mg/kg/day to CFA-induced arthritic rats for 2 weeks. The normal and arthritic control groups were orally given the same equivalent volume of a vehicle (1% carboxymethyl cellulose) in which treatment agents were dissolved. At the end of the experiment, blood samples were collected from the jugular vein for the detection of the total leukocyte count (TLC) and differential leukocyte count (DLC) in blood and the detection of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), tumor necrosis factor-α (TNF-α), interleukin-13 (IL-13), and interleukin-17 (IL-17) levels by enzyme-linked immunosorbent assay (ELISA), as well as markers of oxidative stress and the antioxidant defense system in serum. The right hind ankle regions of three rats from each group were dissected out and fixed in 10% neutral-buffered formalin for histological examination and the other three were kept at -30 °C for Western blot analysis of nuclear factor-kappa B (NF-κB) protein 50 (NF-κB p50), NF-κB p65, inducible nitric oxide synthase (iNOS), nuclear factor erythroid-2-related factor 2 (Nrf2), and matrix metalloproteinase (MMP)-1 (MMP-1), MMP-3, and MMP-9. The CFA injection was deleterious to the ankle joint's histological architecture, manifesting as infiltration of inflammatory cells into the articular cartilage, hyperplasia of the synovium, and erosion of the cartilage. All these effects were ameliorated by diosmin and/or trolox, with the combined dose being the most effective. The two compounds significantly lowered the elevated serum levels of RF, ACPA, TNF-α, and IL-17, as well as other pro-inflammatory mediators, such as NF-κB p50, NF-κB p65, iNOS, MMP-1, MMP-3 and MMP-9. They also increased the levels of the anti-inflammatory cytokine, IL-13, and the cytoprotective transcription factor Nrf2. The compounds stimulated higher activities of antioxidants, such as glutathione, glutathione-S-transferase, catalase, and superoxide dismutase, and reduced lipid peroxidation in the serum of arthritic rats. In conclusion, diosmin, trolox, and their combination, which was the most potent, exerted anti-arthritic, anti-inflammatory and antioxidant effects by suppressing NF-κB signaling, inhibiting matrix metalloproteinases, and activating Nrf2.
RESUMO
This study evaluated the protective effect of kaempferol, a natural flavonoid, against cadmium chloride (CdCl2)-induced liver damage and examined the possible anti-inflammatory and antioxidant mechanisms of protection. Adult male rats were divided into 4 groups (each of 8 rats) as control, kaempferol (50 mg/kg/day orally), CdCl2 (15 ppm/day), and CdCl2 (15 ppm/day) + kaempferol (50 mg/kg/day). All treatments were given for 30 days. With no effect on attenuating the reduced food intake, kaempferol significantly increased body weight and lowered serum levels of liver injury markers including bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase 1 (γ-GTT1) in the CdCl2-treated rats. It also restored normal liver architectures, prevented hepatocyte, loss, and swelling and reduced inflammatory cell infiltration. These effects were associated with a reduction in mitochondrial permeability transition pore, as well as in the expression of cytochrome-c and cleaved caspase-3, markers of mitochondrial damage, and intrinsic cell death. In both the control positive and CdCl2-treated rats, kaempferol significantly lowered the hepatic levels of reactive oxygen species, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), Interleukine-6 (IL-6), and the nuclear activity and localization of NF-κB p65. Besides, kaempferol significantly increased the hepatic total and nuclear levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1, as well as levels of superoxide dismutase (SOD) and reduced glutathione (GSH) but reduced the cytoplasmic protein levels of keap1. In conclusion, the protective effect of kaempferol against CdCl2-induced hepatic damage is mediated by antioxidant and anti-inflammatory effects driven by upregulating Nrf2/HO-1 axis and suppressing the NF-κB p65 and keap1.
Assuntos
Cloreto de Cádmio , Fator 2 Relacionado a NF-E2 , Animais , Cloreto de Cádmio/metabolismo , Cloreto de Cádmio/toxicidade , Quempferóis/metabolismo , Quempferóis/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , RatosRESUMO
This study evaluated if salidroside (SAL) alleviates high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) by downregulating miR-21. Rats (n = 8/group) were treated for 12 weeks as normal diet (control/ND), ND + agmoir negative control (NC) (150 µg/kg), ND + SAL (300 mg/kg), HFD, HFD + SAL, HFD + compound C (an AMPK inhibitor) (200 ng/kg), HFD + SAL + NXT629 (a PPAR-α antagonist) (30 mg/kg), and HFD + SAL + miR-21 agomir (150 µg/kg). SAL improved glucose and insulin tolerance and preserved livers in HFD-fed rats. In ND and HFD-fed rats, SAL reduced levels of serum and hepatic lipids and the hepatic expression of SREBP1, SREBP2, fatty acid (FA) synthase, and HMGCOAR. It also activated hepatic Nrf2 and increased hepatic/muscular activity of AMPK and levels of PPARα. All effects afforded by SAL were prevented by CC, NXT629, and miR-21 agmoir. In conclusion, activation of AMPK and upregulation of PPARα mediate the anti-steatotic effect of SAL.
RESUMO
This study evaluated the nephroprotective effect of kaempferol against cadmium chloride (CdCl2) -induced nephropathy in rats. It also investigated if activation of Nrf2 is a common mechanism of action. Adult male rats ((150 ± 15 g) were divided into 4 groups (n = 8/each) as a control (1% DMSO, orally), control + kaempferol (200 mg/kg, orally), CdCl2 (50 mg/l in drinking water), and CdCl2 + kaempferol (200 mg/kg)-treated rats. All treatments were conducted for 8 weeks. Kaempferol significantly attenuated CdCl2-induced weight loss, reduction in kidney weights, and the injury in the glomeruli, proximal tubules, and distal tubules in the treated rats. It also significantly lowered serum levels of urea and creatinine, increased urine output and urinary creatinine levels and clearance but reduced urinary levels of albumin urinary albumin exertion (UAER), and urinary albumin/creatinine ratio (UACR) in these rats. In parallel, kaempferol downregulated renal levels of cleaved caspase-3 and Bax and unregulated those of Bcl2. In the kidney tissues of the control animals and CdCl2 rats, kaempferol significantly attenuated oxidative stress, inflammation and significantly boosted levels of manganese superoxide dismutase and glutathione. Also, and in both groups, kaempferol suppressed the nuclear levels of NF-κB p65, downregulated Keap1, and stimulated the nuclear activation and protein levels of Nrf2. In conclusion, kaempferol is a potential therapeutic drug to prevent CdCl2-induced nephropathy due to its anti-inflammatory and anti-oxidant effects mediated by suppressing NF- NF-κB p65 and transactivating Nrf2.
Assuntos
Cloreto de Cádmio , Quempferóis , Nefropatias , NF-kappa B , Animais , Masculino , Ratos , Albuminas/metabolismo , Antioxidantes/metabolismo , Cloreto de Cádmio/farmacologia , Creatinina , Quempferóis/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim , Nefropatias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse OxidativoRESUMO
BACKGROUND: Protein kinase R (PKR) can suppress various types of solid tumors by inducing cellular oxidative stress and apoptosis. Likewise, Slaidorside, a plant flavonoid, was shown to have anti-tumorigenesis in many solid tumors. OBJECTIVE: This study evaluated anti-tumorigenesis of Salidroside in HT29 colorectal cancer and investigated if the underlying mechanism involves activation of PKR. METHODS: Control or PKR deficient cells were cultured in DMEM media treated with 100 µM Salidroside and cell survival, apoptosis, and other biochemical-related markers were evaluated. RESULTS: Salidroside significantly reduced cell survival and proliferation and increased the release of lactate dehydrogenase (LDH) and levels of single-stranded DNA (ssDNA). It also increased the protein levels of caspases 3 and 8. Concomitantly, Salidroside increased the protein level and activity of PKR and increased the expression of its downstream targets, p-eIF2α (Ser51), p53 MAPK, and p53. On the contrary, it inhibited the nuclear activation of STAT-3 and NF-κB p65. In PKR deficient cells, the partial effects of Salidroside on cell survival, proliferation, and apoptotic markers were observed coincided with no effects on the expression of eIF-2α, and JNK, p53, p38 MAPK, and caspase 8 but with a significant decrease in the nuclear activities of STAT3 and NF-κB. CONCLUSION: Salidroside suppresses the tumorigenesis of HT29 CRC by increasing activation of eIF-2α and JNK and upregulation of p53, p38 MAPK, and caspase-8 through upregulating and activation of PKR. However, the tumor suppressor effect of Salidroside requires also inhibition of STAT3 and NF-κB in a PKR-independent mechanism.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Glucosídeos/uso terapêutico , Células HT29/efeitos dos fármacos , NF-kappa B/metabolismo , Fenóis/uso terapêutico , Rhodiola/química , Fator de Transcrição STAT3/metabolismo , eIF-2 Quinase/metabolismo , Glucosídeos/farmacologia , Humanos , Fenóis/farmacologiaRESUMO
Cadmium (Cd) is associated with non-alcoholic fatty liver disease (NAFLD). The hepatic activation of p53/miR-43a-induced suppression of SIRT1/FXR axis plays a significant role in the development of NAFLD. In this study, we have investigated CdCl2-induced NAFLD in rats involves activation of miR34a/SIRT1/FXR axis. Adult male rats were divided into 4 groups (n-8/each) as a control, CdCl2 (10 mg/l), CdCl2 + miR-34a antagomir (inhibitor), and CdCl2 + SRT1720 (a SIRT1 activator) for 8 weeks, daily. With no effect on fasting glucose and insulin levels, CdCl2 significantly reduced rats' final body, fat pads, and liver weights, and food intake. Concomitantly, it increased the circulatory levels of liver markers (ALT, AST, and γ-GTT), increased the serum and hepatic levels of total cholesterol and triglycerides coincided with increased hepatic lipid accumulation. Besides, it increased the mRNA and protein levels of SREBP1, SREBP2, FAS, and HMGCOA reductase but reduced mRNA levels of PPARα, CPT1, and CPT2. Interestingly, CdCl2 also increased mRNA levels of miR34 without altering mRNA levels of SIRT1 but with a significant reduction in protein levels of SIRT1. These effects were associated with increased total protein levels of p53 and acetylated protein of p53, and FXR. Of note, suppressing miR-34a with a specific anatomic or activating SIRT1 by SRT1720 completely prevented all these effects and reduced hepatic fat accumulations in the livers of rats. In conclusion, CdCl2 induced NAFLD by increasing the transcription of miR-34a which in turn downregulates SIRT1 at the translational level.
Assuntos
Cloreto de Cádmio/efeitos adversos , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Fígado/metabolismo , Masculino , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Proteínas de Ligação a RNA , Ratos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53RESUMO
Inflammatory skin diseases are highly prevalent, yet their impacts on patients' quality of life (QoL) are not addressed. In this cross-sectional study, the Arabic version of Skindex-16 was used to evaluate the symptomatic, emotional, and functional distress of patients with inflammatory skin disorders attending several outpatient dermatology clinics in Egypt and Saudi Arabia. Patients with ≥50% of the symptoms score, ≥50% of the emotions score, and ≥33% of the functioning score were considered having poor QoL. A total of 1,310 patients aged 30 ± 13 years (70.6% from Egypt and 29.4% from Saudi Arabia) were included in this study. Of them, 1,192 patients had inflammatory skin diseases, and 118 had facial nevi, who served as controls. Patients with inflammatory skin diseases had significantly worse QoL than those with nevi. Autoimmune bullous disease group showed the highest prevalence poor symptoms (56.8%), poor emotions (75.7%), and poor functioning (83.8%) of QoL. Women with acne and psoriasis were more likely to have poor symptoms than men (16.3% vs. 4.7% and 52.7% vs. 25.3%, respectively). In conclusion, inflammatory skin diseases had profound negative effects on patients' QoL. Age, sex, education, and marital status of patients can affect their perception of QoL.
Assuntos
Acne Vulgar , Dermatite , Dermatopatias , Acne Vulgar/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Qualidade de Vida , Dermatopatias/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Ethephon (EP) is the most famous plant growth regulator with different adverse effects on kidney function. Virgin Olive Oil (VOO) is considered as a natural source of antioxidant with beneficial effects. Thus, this study was conducted to investigate the effects of VOO on nephrotoxicity induced by EP in rats. METHODS AND MATERIALS: In this study, 80 male rats (weighing 200-250â¯g) were divided into four groups including I: control group received normal saline as vehicle, II: received VOO, III: received EP (150â¯mg/kg/day) for 2 months, IV: received EP (150â¯mg/kg/day for 2 months, after 2-month pretreatment with VOO. VOO (2â¯mL/kg/day) and vehicle were administered by gastric gavage for 2 months. At the end, the animals were sacrificed, and their blood and kidneys were used for examinations. Isolated kidneys were used for histopathological and oxidative stress studies. RESULTS: Significant increases were recorded in blood (neutrophils, monocytes) and urinary parameters as well as malondialdehyde (MDA) content in the group III compared to groups II and I (PË0.05). Antioxidant enzymes significantly declined and histopathological alterations increased in the group III. In the group IV, significant decreases were recorded in blood and urinary parameters, MDA, and histopathological alterations and a significant increase were found in antioxidant enzymes compared to group III (PË0.05). CONCLUSIONS: Findings of the present study demonstrated protective effects of VOO in prevention of kidneys against EP -induced toxicity in albino rats.
RESUMO
Many aspects linked to personal characteristics, society and culture constitute some of the motivators that drive food choice. The aim of this work was to determine in what extent the eating behaviors of individuals are shaped by six different types of determinants, namely: health, emotions, price and availability, society and culture, environment and politics, and marketing and commercials. This is a descriptive cross-sectional study, involving a non-probabilistic sample of 11,960 participants from 16 countries. The objective of this work was to validate the questionnaire, so as to make it suitable for application in different contexts and different countries. For that, six scales were considered for validation by confirmatory factor analysis with structural equation modelling. The obtained results showed that the six individual scales evaluated presented good or very good fitting indices, with saturation in goodness-of-fit index in all cases. The values of chi-square ratio were 6.921 (for health), 0.987 (environment), 0.610 (emotions) and 0.000 in the remaining cases (convenience, society, marketing). Furthermore, the fit was perfect, with saturation for all indices, in three of the six models (convenience, society and marketing). The results of this wok allowed the validation of the six scales, and the assessing of different types of factors that can influence food choices and eating behaviors, namely in the categories: health, emotions, price and availability, society and culture, environment and politics, and marketing and commercials.