Studies on the protective effect of ambrex on drug induced hepatotoxicity an in vitro and in vivo approach

Abstract

Liver performs multiple metabolic functions and drug induced hepatic injury is the most important reason for withdrawal of an approved drug. Polyherbal formulations with many active ingredients, antioxidants and newlinebeneficial phytochemicals act synergistically in treatment of diseases and also as supplements to protect from the side effects of drugs. For the above said reasons, research on polyherbal formulation is gaining importance in the recent days. In this study, Ambrex (a licensed drug) an amber based polyherbal formulation was mainly characterised to establish its safety and efficacy in managing drug induced toxicity. newlineStudies were carried out in in vitro and in vivo to establish its hepatoprotective effect in three different toxic conditions. The commonly used analgesic acetaminophen, at high doses damages the liver mainly by oxidative stress. Methotrexate, an anticancer drug induces direct toxicity to liver by inhibition of dihydrofolate reductase, which leads to arrest of DNA and RNA synthesis which causes cellular damage. It also indirectly induces liver damage by means of oxidative stress. D-Galactosamine a standard hepatotoxin, causes diffuse liver damage that resembles conditions of viral hepatitis. It mainly induces liver injury due to transcriptional arrest, by whichthe protein synthesis in the liver is inhibited, and also due to increase in oxidative and nitrosative stress, which results in inflammatory responses. So, these three compounds were used to induce hepatocellular damage in Chang liver cells and in mice models. Since the standard drug Silymarin is a potent antioxidant, this was used as reference drug for acetaminophen induced toxicity. Liv.52, a polyherbal drug was used for D-Galactosamine andmethotrexate induced cellular damage as reference drug. newline newline