Introduction: Liver is an important organ in the body. Due to its role in metabolism of drugs it is also a major site of drug induced liver injury. Oxidative stress plays an important role in DILI therefore use of nti-oxidants has been proposed to combat liver injury .

Objective of the Study: To measure and compare Hepatoprotective effects of Zinc complex of Betulinic acid and Silymarin due to their antioxidant effects on Pyrazinamide induced Hepatotoxicity in mice.

Methodology: It was an experimental randomized control trial. The research was conducted at the Department of Pharmacology and Therapeutics and Multidisciplinary research laboratory at IIMCT with mutual collaboration of National Institute of Health (NIH) in Islamabad, Pakistan. Research was started after the official approval of synopsis by accredited Ethical Review Committee. Study duration was one year from 1 September 2020 to 31 august 2021. 24 adult Balb-C mice were randomly divided into four groups. Group 1 was Negative Control (NC) and did not receive any intervention. Oral pyrazinamide (500mg/kg) was administered for 28 days to the group 2 (disease control) alone and to group 3 and 4 in combination with Silymarin (100mg/kg) and Zinc complex of Betulinic Acid(1mg/kg) respectively. Mice were dissected after completion of experiment and liver samples were taken for Histopathological analysis. Hepatoprotective function of Silymarin and zinc complex of Betulinic acid was evaluated in group 3 and 4 by Histopathological changes.

Results: Significant (p<0.05) changes were seen in parameters (necrosis, inflammatory cell infiltration and vascular congestion) among groups.

Conclusion: This study proves protective effects of zinc complex of Betulinic acid and Silymarin on pyrazinamide induced hepatotoxicity.

Key Words: Hepatotoxicity, Betulinic Acid, Silymarin, Pyrazinamide, Zinc, Tuberculosis