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Artemether/lumefantrine/tinidazole (A/L/T) has shown additive antiplasmodial activity; therefore its safety assessment is imperative. This study examined its hepatotoxic effect on healthy and diseased mice. Fifty four Swiss albino mice of n=6 were used. The mice were diseased with Plasmodium berghei ( ) and treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 4 days, respectively. Healthy mice were treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 28 days, respectively. After drug treatment; the mice were weighed and anesthetized. Liver samples were excised, weighed and evaluated for oxidative stress indices and histology. Blood samples were assessed for serum liver function indices. Treatment with T, A/L and A/L/T produced no significant (p>0.05) effects on all evaluated parameters in parasitized mice when compared to control. Significant decrease in body weight with significant increase in liver weight occurred in healthy mice treated with A/L (p<0.05) and A/L/T (p<0.01) when compared to control. Impaired liver function characterized by significantly increased serum aminotranferases, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, and bilirubin levels with significantly decreased total protein and albumin levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. Significantly decreased glutathione peroxidase, superoxide dismutase, glutathione, and catalase levels with significantly increased malondialdehyde levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. A/L/T caused hepatocyte necrosis in healthy mice. The use of A/L/T for malaria treatment seems safe on the liver, but may impair liver function with prolonged use.
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