Sequence-dependent modulation of hepatorenal biochemical markers following Artemether-Lumefantrine and Sulfadoxine-Pyrimethamine exposure in Wistar rats

Abstract

Malaria remains one of the most pressing health problems, especially in Sub-Saharan Africa. Various antimalarial drugs, used to combat this debilitating illness, may directly or indirectly affect blood indices in humans. This study aims to evaluate the toxicological effects of sequential administration of Artemether-lumefantrine and sulfadoxine-pyrimethamine in male Wistar rats. Thirty (30) mature male Albino Wistar rats weighing between 190-280g were randomly divided into five groups comprising six (6) rats each. Group 1 served as control, Group 2 received Artemether-lumefantrine (8 mg/kg/bw) for 3 days, Group 3 received sulfadoxine-pyrimethamine (0.079 mg/kg/bw) for 1 day, Group 4 received a sequential dose of Artemether-Lumefantrine for 3days and sulfadoxine-pyrimethamine for 1 day, while Group 5 received a sequential dose of SP for 1 day and AL for 3 days. Sequential administration of AL and SP resulted in a significant (p < 0.05) elevation of ALT, AST, ALP, serum total and direct bilirubin levels, urea, creatinine, and HDL. There was a significant (pL0.05) decrease in the serum total protein and albumin. Notably, HDL levels increased significantly in the SP [->] AL group (p < 0.05), while other lipid parameters showed sequence-specific significant changes compared to the control. Sequential administration, particularly the SP [->] AL sequence, was observed to have more pronounced effects on hepatorenal biomarkers compared to independent administration. These findings are relevant, especially in malaria-endemic regions where unregulated self-medication and drug switching are rampant.