Evaluation of ameliorative ability of Silibinin against zidovudine and isoniazid-induced hepatotoxicity and hyperlipidaemia in rats: Role of Silibinin in Phase I and II drug metabolism

摘要

Abstract HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as “Milk thistle” is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH?+?AZT-induced toxic insults to liver of rats. Wistar albino rats (n?=?6/groups) were given INH and AZT (25 and 50?mg?mg/kg b.w.) respectively either alone or in combination for a sub-chronic period of 45 days orally. Another group of rats received SBN (100?mg/kg b.w.) along with INH and AZT. The group that received propylene glycol served as control. AZT alone, INH alone and INH?+?AZT treatments showed parenchymal cell injury and cholestasis by highly significant increase in the activities of marker enzymes (aspartate and alanine transaminase, alkaline phosphatase, argino succinic acid lyase), bilirubin and protein. The presence of hyperlipidaemia was observed by analyzing lipid profiles in serum/liver/adipose tissue, gene expression (RT-PCR) of Phase-I and II metabolizing enzymes and western blot. Transmission electron microscopy study also revealed large vacuoles with membraneous debri, pleomorphic mitochondria, disruption of endoplasmic reticulum, presence of lipid droplets, breakage in cellular and nuclear membrane. SBN simultaneous treatment showed ameliorative effect against INH?+?AZT-induced hepatotoxicity and hyperlipidemia in rats. Graphical abstract Display Omitted Highlights of the study ? SBN ameliorates INH?+?AZT-induced hepatotoxicity. ? SBN protects liver from hyperlipidaemia. ? INH toxicity gets augments with AZT treatment. ? Phase I metabolizing enzymes has major role in lipid metabolism.