Safety Assessment of Artemether/Lumefantrine/ Tinidazole on the Kidneys of Healthy and Diseased Mice

Abstract

Artemether/lumefantrine/tinidazole- (A/L/T) can be use for the treatment of malaria; therefore its safety assessment is imperative. This study assessed its safety on the kidneys of healthy and diseased mice. Fifty four Swiss albino mice were used for this study. 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. Healthy mice were treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 28 days. At the termination of treatment, the mice were weighed, sacrificed and blood samples were collected and examined for kidney biochemical markers. Kidneys were weighed and evaluated for oxidative stress markers and histology. T, A/L and A/L/T had no significant (p>0.05) effects on all evaluated parameters in diseased mice when compared to control. Body weight was decreased whereas kidney weight was increased in healthy mice treated with T, (p<0.05), A/L (p<0.05) and A/L/T (p<0.01) when compared to control. Significantly elevated serum creatinine, urea, uric acid levels with significantly decreased albumin, and total protein 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. Altered kidney oxidative stress markers characterized by significantly decreased glutathione, catalase, glutathione peroxidase, superoxide dismutase 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 produced tubular necrosis and enlarged Bowman’s space in healthy mice. The use of A/L/T as an antimalarial drug may be safe on the kidney, but long term use may cause kidney damage.