Livogrit Ameliorates Thioacetamide-Induced Liver Fibrosis and Dyslipidemia in Rat Model by Regulating Oxidative Stress and Hepatic Collagen Levels, in a Non-Mutagenic Manner

Background: Liver fibrosis represents a serious health challenge and is the outcome of chronic liver diseases like cirrhosis and hepatitis. This study was designed to evaluate the anti-fibrotic and anti-dyslipidemic effects of Livogrit (a tri-herbal formulation) on Thioacetamide (TAA)-induced rat model of fibrosis; and its mutagenic potential in Ames test. Methods: The study employed TAA-induced Sprague-Dawley rat to evaluate Livogrit’s anti-fibrotic potentials, as well as associated dyslipidemia. Quantification of phytometabolites present in Livogrit was conducted using UHPLC-DAD analysis. The pharmacological effects of Livogrit were assessed by measuring hepatic enzyme markers AST, ALT, and ALP; serum lipid profile markers TG, TC, HDL, and LDL; anti-oxidative enzymes SOD and catalase. In addition, histopathological changes in hepatic tissue were assessed. Changes in body weight, relative liver weight, hydroxyproline, and collagen levels were also evaluated. Silymarin served as the experimental reference standard. Finally, Livogrit was also tested for its mutagenic potential through Ames assay. Results: UHPLC-DAD analysis of Livogrit revealed presence of several bioactive metabolites. Livogrit effectively attenuated TAA-induced hepatotoxicity and fibrosis. Treatment with Livogrit reduced elevated ALT, AST, ALP, TG, TC, LDL, nitrite, hydroxyproline, and collagen levels while improving HDL, SOD, and catalase levels. Livogrit also regulated LDL/HDL and TC/HDL ratios. Livogrit treatment normalized the detrimental effects of TAA on the liver histo-architecture, in terms of inflammatory and fibrotic changes. Ames test also confirmed that Livogrit was non-mutagenic at highest tested concentration, with or without metabolic (S9) activation. Conclusion: Livogrit demonstrated preclinical potential for the effective management of hepatic fibrosis and dyslipidemia, in a non-mutagenic manner. This study paves a way for detailed non-clinical safety experiments and clinical investigations of Livogrit in patients with hepatic fibrosis under controlled conditions. Keywords: liver fibrosis, dyslipidemia, Livogrit, thioacetamide, histopathology, Ames assay, UHPLC