RESUMO
The present study aims to evaluate the protective effect of grape seed proanthocyanidins (GSP) on cadmium (Cd)-induced testicular apoptosis, inflammation, and oxidative stress in rats. A total of 24 male Wistar rats were divided into four groups, namely control, GSP (100 mg/kg BW), Cd (5 mg/kg BW), and Cd+GSP. Cd-treated rat testes exhibited a significant increment in oxidative stress mediated inflammation and apoptosis. Pre-administration of GSP exhibit significant protection against the apoptotic and inflammatory damages elicited by Cd and uphold the intercellular antioxidant status in testes. Histological changes were studied and the immunohistochemical staining for caspase 3, HSP70, and eNOS protein expressions were also analyzed to justify the protective action of GSP. Furthermore, GSP prevented DNA damage, and enhanced the expression of antioxidant responsive elements Nrf2/HO-1 by PI3K/Akt-dependent pathway. Therefore, our results suggest that GSP acts as a multipotent antioxidant entity against Cd-induced oxidative testicular toxicity in rats.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cádmio/toxicidade , Extrato de Sementes de Uva/farmacologia , Proantocianidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Apoptose , Caspase 3/genética , Caspase 3/metabolismo , Dano ao DNA , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Transdução de Sinais/genética , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/citologia , Testículo/metabolismoRESUMO
The present study was designed to investigate the neuroprotective effect of hesperetin (Hp) against cadmium (Cd)-induced neurotoxicity in rats. Cadmium (3 mg/kg body weight (b.w.), subcutaneous) administration for 3 weeks demonstrated neurotoxicity in rats by the decreased activity of acetylcholinesterase in the brain. The oxidative stress markers (thiobarbituric acid reactive substances and protein carbonyls) were significantly increased with decreased enzymatic (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase) and non-enzymatic antioxidants (reduced glutathione, total sulphydryl groups and vitamin C). The proteolytic and membrane-bound enzymes (Na+ K+-ATPase, Mg2+-ATPase and Ca2+-ATPase) were also decreased with increased apoptotic markers (Bcl2 Associated X Protein (Bax), cytochrome C, caspase 3 and 9) and decreased anti-apoptotic marker (B-cell lymphoma 2 (Bcl2)) in the brain of Cd-treated rats. Moreover, Cd administration significantly decreased the mitochondrial electron transport chain complexes (I, II, III and IV) in the brain of rats. Preadministration of Hp (40 mg/kg b.w., oral) significantly attenuated the Cd-induced oxidative stress and mitochondrial dysfunction, restored the antioxidant and membrane-bound enzyme activities and decreased apoptosis in the brain of rats.
Assuntos
Encéfalo/efeitos dos fármacos , Cádmio/toxicidade , Hesperidina/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The present study has been designed and carried out to explore the role of grape seed proanthocyanidins (GSP) in the pancreas of cadmium (Cd)-induced cellular oxidative stress-mediated toxicity in rats. Four groups of healthy rats were given oral doses of Cd (5-mg/kg BW) and to identify the possible mechanism of action of GSP 100-mg/kg BW was selected and was given 90 min before Cd intoxication. The causative molecular and cellular mechanism of Cd was determined using various biochemical assays, histology, western blotting and ELISA. Cd intoxication revealed increased levels of proinflammatory cytokines (TNF-α, IL1ß and IFN-γ), reduced levels of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2 and GLUT-4) along with the enhanced levels of signaling molecules of apoptosis (cleaved Caspase-12/9/8/3) in the pancreas of Cd-intoxicated rats. Results suggested that the treatment with GSP reduced blood glucose level, increased plasma insulin and mitigated oxidative stress-related markers. GSP protects pancreatic tissue by attenuated inflammatory responses and inhibited apoptosis. This uniqueness and absence of any detectable adverse effect of GSP proposes the possibility of using it as an effective protector in the oxidative stress-mediated pancreatic dysfunction in rats.
