Kidney Toxicity Studies in Mice (BALB/c) Recurrently infected with Plasmodium berghei and treated with either artemether plus lumefantrine (AL) or artesunate plus amodiaquine (AA)

Abstract

Individuals living in areas where malaria is prevalent are often exposed to the disease and subsequently treated. This frequent exposure to malaria and its treatment could put a strain on the kidneys, which are responsible for eliminating metabolites, possibly leading to oxidative stress, and potentially impairing their function. Hence, this study explored the potential consequences of repeated exposure to malaria parasites and treatment with artemether plus lumefantrine (AL) or artesunate plus amodiaquine (AA) on kidney oxidative stress and functional markers. Three groups of randomly assigned male mice were used: the control group was given distilled water, whereas the other two groups were infected with Plasmodium berghei and treated with either AL or AA for six consecutive periods. Examination of the study parameters was carried out on the blood and kidney tissues after the initial, third, and sixth exposure intervals. Concentration of malondialdehyde (MDA) in the kidneys was significantly higher in mice exposed to P. berghei and treated with either AL (p < 0.001) or AA (p < 0.01) after the first, third, and sixth exposures than in the control group. Activities of kidney glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) increased considerably (p < 0.001) following the third and sixth exposures to P. berghei and AL or AA. Increases in MDA, GPx, SOD, and CAT levels did not follow a consistent upward trend. Moreover, no significant differences (p > 0.05) were observed in the levels of plasma sodium, potassium, chloride, and creatinine between the groups exposed to P. berghei and treated with AL or AA and the control group after the sixth exposure. Histological analysis showed evidence of glomerulus oedema in the kidney tissue of mice infected with P. berghei and treated with AL or AA for the first, third, and sixth exposure periods. Mice repeatedly exposed to malarial parasites and AL or AA therapeutic treatment showed higher kidney lipid peroxidation during consecutive exposures, with elevated levels of GPx, SOD, and CAT activity in the kidneys, potentially protecting against lipid peroxidation and preserving renal function. Nevertheless, the observed antioxidant activity proved to be inadequate in preventing glomerular oedema.