Acetaminophen-induced hepato- and nephrotoxicity and amelioration by hydroalcoholic polyherbal formulation in experimental rodents

Abstract

Objective: The objective of this study was to evaluate hepato- and nephroprotective potential of extracts of polyherbal formulations against acetaminophen (paracetamol [PCM])-induced dysfunction in experimental rodents. Materials and Methods: Acute and subacute toxicity study of hydroalcoholic polyherbal formulation (HAF) was performed according to the OECD guidelines. Sprague Dawley female rats were grouped into three containing six animals each for acute toxicity study. For subacute toxicity study, animals were observed periodically for the symptoms of toxicity and death within 24 h and then daily for 14 days. Acetaminophen-induced hepato- and nephrotoxicity models were used for this study. Hepatotoxicity and nephrotoxicity were performed it to control group rats received normal saline (p.o.) per day for 7 days. Hepatotoxicity and nephrotoxicity induced by acetaminophen (PCM) were administered at a dose of 750 mg/kg/day/oral for 7 day and Groups III & IV were treated with PCM (750 mg/kg/day/oral) and HAF of doses 200 and 400 mg/kg/day/oral for 7 days respectively. The liver weight, kidney weight, liver function test, and kidney function test were evaluated along with histopathological investigation in various experimental groups of rats. Results: It was observed that the PCM treatment induced significant elevation (P < 0.001) in creatinine, kidney weight, liver weight, and liver functions such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and triglycerides. Treatment of HAF of doses 200 and 400 mg/kg/d (p.o) for 7 day) on experimental rats recorded significant decrement (up to P < 0.001) in creatinine, kidney weight, liver weight, and liver functions such as ALT and AST. The doses of 400 mg/ kg/body weight/oral of HAF were found significant when compare with at doses of 200 mg/kg/body weight/oral. A histological observation of liver and kidney tissues provides positive response on experimental groups having PCM + HAF 400 mg/kg-induced model and significant data also correlate the biochemical parameters. Conclusions: This finding powerfully supports that polyherbal formulation acts in the liver and kidney as a potent scavenger of free radicals to prevent the toxic effects of PCM. The biochemical and histopathological parameters of polyherbal formulation validate its ethnomedicinal uses and polyphenolic presence.