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Drug-induced hepatotoxicity (DIH) accounts for 9.5% of all suspected adverse drug reactions and are the most common reason for withdrawal of a drug from the market. The liver is a central metabolizing organ so it more susceptible to metabolism-dependant injury. Thus, injury may be a direct toxic effect or immunological reaction to either the drug or an active metabolite formed by bioactivation. [1] It is reported that 62% of withdrawn drugs have toxic metabolites. [2] Although, with the exception of rare cases, DIH subsides after cessation of treatment with the drug, which represents an important diagnostic and therapeutic challenge for physicians. Simvastatin (SMT) competitively inhibits HMG-CoA to mevalonate. Mevalonate is also a precursor of Coenzyme Q10 (CoQ10). Thus, treatment with statins could also lower its levels. CoQ10 acts as an antioxidant, has membrane stabilising effects, and is important for cellular mitochondrial respiration, which is essential for energy production in organs. [3,4] Thus, simvastatin causes oxidative ABSTRACT Objective: This study was designed to assess the effect of polyherbal formulation (PHF) on simvastatin hepatotoxicity in rats and to assess the possibility of co-administration of PHF along with hepatotoxic drugs. Methods: Hepatotoxicity in rats was induced by simvastatin (20 mg/kg p.o. for 30 days) and the protective effect of PHF (0.25 ml/kg/p.o. and 0.5 ml/kg/p.o. either along with drug or followed by inducing hepatotoxicity) was identiÞ ed by estimating marker enzymes for liver function such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ glutamic transpeptidase; oxidative stress markers such as lipid peroxidation, reduced glutathione, super oxide dismutase, and catalase; and protein proÞ le such as total bilirubin, direct bilirubin, total albumin, and total protein. A histopathological study was also carried out to conÞ rm hepatotoxicity. Results and Discussions: Simvastatin hepatotoxicity was characterized by a signiÞ cant increase in oxidative stress along with marker enzymes of liver function and depletion of proteins. Administration of PHF either along with simvastatin or followed by inducing hepatotoxicity signiÞ cantly improved the level of marker enzymes for liver function, oxidative stress, and protein proÞ le. Conclusion: The study suggests a protective role of PHF on simvastatin hepatotoxicity and it can be utilized to treat hepatotoxicity with long-term clinically useful drugs.

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