RESUMO
Paracetamol (PCM) hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress; natural antioxidant compounds have been tested as an alternative therapy. This study evaluated the hepatoprotective activity of an alcoholic extract of Boswellia ovalifoliolata (BO) bark against PCM-induced hepatotoxicity. BO extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2, 2-diphenyl-1-picrylhydrazyl. Administration of PCM caused a significant increase in the release of transaminases, alkaline phosphatase, and lactate dehydrogenase in serum. Significant enhancement in hepatic lipid peroxidation and marked depletion in reduced glutathione were observed after parac intoxication with severe alterations in liver histology. BO treatment was able to mitigate hepatic damage induced by acute intoxication of PCM and showed a pronounced protective effect against lipid peroxidation, deviated serum enzymatic variables, and maintained glutathione status toward control. The results clearly demonstrate the hepatoprotective effect of BO against the toxicity induced by PCM.
Assuntos
Antioxidantes/uso terapêutico , Boswellia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Acetaminofen/efeitos adversos , Fosfatase Alcalina/sangue , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Compostos de Bifenilo/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa/metabolismo , L-Lactato Desidrogenase/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Picratos/metabolismo , Casca de Planta , Extratos Vegetais/farmacologia , Ratos Wistar , Transaminases/sangueRESUMO
OBJECTIVE: To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule (EtAc-LME) in MKN-74, NUGC gastric cancer cells and non cancerous gastric mucous cells (GES-1), and to explore the mechanism of EtAc-LME induced apoptosis. METHODS: The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases, PARP cleavage, expression of cytochrome-c (Cyt-c) was determined by western blotting, mRNA expression of Bcl-2, Bax by RT-PCR, loss of mitochondrial potential using DiOC6 dye, annexin binding assay and its influence on cell cycle arrest by flow cytometry. RESULTS: The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells (NUGC and MKN-74) compared to normal gastric cells (GES-1), suggesting more specific cytotoxicity to the malignant cells. Over expression of Cyt-c and subsequent activation of caspases-3 and down regulation of Bcl-2 and loss in mitochondrial potential in EtAc-LME treated MKN-74 and NUGC cells suggested that EtAc-LME induced apoptosis by mitochondrial dependent pathway. CONCLUSIONS: The present findings suggest that ethyl acetate extract of Memecylon edule induces apoptosis selectively in gastric cancer cells emphasizing the importance of this traditional medicine for its potential in the treatment of gastric cancer.
