Sequence-dependent Modulation of Hepatorenal Biochemical Markers Following Artemether–lumefantrine and Sulfadoxine–pyrimethamine Exposure in Wistar Rats
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Abstract
Malaria remains one of the most pressing public health challenges, particularly in Sub-Saharan Africa. Antimalarial drugs used in its treatment may influence biochemical markers of hepatic, renal, and metabolic function. This study aimed to evaluate the toxicological effects of the sequential administration of artemether-lumefantrine and sulfadoxine-pyrimethamine in male Wistar rats. Thirty (30) mature male Albino Wistar rats weighing between 190- 280 g 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 3 days 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 (p < 0.05) 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 provide preliminary evidence that the sequence of administration may influence hepatorenal biochemical responses following exposure to these antimalarial drugs.
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