Objectives:The aim of this study is to evaluate the hepatoprotective effect of Lasianthera africana (Icacinaceae) against isoniazid (INH) and rifampicin (RIF)-induced liver damage in rats.Methods:The hepatoprotective effects of hot aqueous L.africana (HALA) leaf extract (0.1-1 g/kg) and silymarin (50 mg/kg) were assessed in a model of oxidative liver damage induced by RIF and INH (100 mg/kg each) in Wistar rats for 28 days.Biochemical markers of hepatic damage such as alanine aminotransferase (ALT),aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed.The antioxidant statuses of plasma glutathione peroxidase (GSPx),glutathione reductase (GSH),catalase (CAT) and superoxide dismutase (SOD) and lipid peroxidation were evaluated.Results:The pretreatment of INH and RIF decreased hematological indices and the antioxidant levels (P ＜ 0.001) and increased the levels of liver marker enzymes (P ＜ 0.001).However,pretreatment with HALA extract and silymarin provoked significant elevation of hematological indices.The levels of AST,ALT,and ALP were depressed (P ＜ 0.001).Total triglycerides,total cholesterol,total bilirubin and low-density lipoprotein were decreased (P ＜ 0.001).However,high-density lipoprotein,bicarbonate,and electrolytes like chloride and potassium were elevated (P ＜ 0.001),but sodium was depressed (P ＜ 0.05).Additionally,GSH,GSPx,SOD and CAT were elevated (P ＜ 0.01) and malondialdehyde was depressed (P ＜ 0.001) when compared to the RIF-INH-treated rats.Histopathological evaluations support hepatoprotective activity.Conclusion:This study demonstrated that HALA leaf extract attenuated RIF-INH-induced hepatotoxicity.L.africana could be exploited in management of RIF-INH-induced hepatitis.