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Pharmacology ; 98(1-2): 29-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27007136

RESUMO

Drug-induced liver injury is a major challenge in treating tuberculosis with isoniazid (INH) and rifampicin (RIF). This study was aimed at evaluating the protective effects of Bacopamonnieri (Brahmi) against INH and RIF-induced hepatotoxicity in a rat model and also to study the patterns of interaction between pregnane X receptor (PXR) and chosen active compounds of B. monnieri. Hepatotoxicity was induced in the experimental animals by the oral administration of INH and RIF (50 mg/kg b.w. each/day) for 28 days. The effects of co-administration of B. monnieri (500 mg/kg b.w./day) in INH- and RIF-induced rats were studied by the estimation of biochemical analyses. The standard hepatoprotective drug silymarin (25 mg/kg b.w./day) was used for the purpose of comparison. In silico docking experiments were carried out using the PatchDock server and the results were analysed on the PyMol molecular viewer. There was significant reduction in the antioxidant status of INH and RIF-induced rats. Also, there was significant elevation in the levels of serum liver function markers in the INH- and RIF-induced rats. B. monnieri was able to normalise the tested parameters. In silico studies reveal significant interaction between PXR and bacopaside I. B. monnieri exerts significant protective effects against INH and RIF-induced hepatotoxicity in rats.


Assuntos
Antituberculosos/efeitos adversos , Bacopa , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Quimioterapia Combinada , Feminino , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Interleucina-10/sangue , Isoniazida/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Simulação de Acoplamento Molecular , Ratos Wistar , Rifampina/efeitos adversos , Superóxido Dismutase/metabolismo
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