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 residing in regions where malaria is endemic are frequently exposed to the disease and subsequently treated. The frequent exposure to malaria and its treatment could exert a deleterious effect on the kidneys, which are responsible for eliminating metabolites. This could potentially lead to oxidative stress and impair their function. Therefore, this study aimed to investigate 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 male mice were randomly assigned for the study: the control group was administered distilled water, while the other two groups were infected with berghei Plasmodium berghei and treated with either AL or AA for six consecutive periods. The study parameters were examined in the blood and kidney tissues following the initial, third, and sixth exposure intervals. The 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. Following the third and sixth exposures to P. berghei and AL or AA, there was a considerable increase (p<0.001) in the activities of kidney glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). The observed increases in MDA, GPx, SOD, and CAT levels did not follow a consistent upward trend. Furthermore, no statistically significant differences (p>0.05) were identified in the plasma levels of sodium, potassium, chloride, and creatinine between the groups exposed to P. berghei and treated with AL or AA and the control group following the sixth exposure. Histological analysis revealed the presence of glomerular edema in the kidney tissue of mice infected with P. berghei and treated with AL or AA during the initial, third, and sixth exposure periods. Mice that were repeatedly exposed to malarial parasites and treated with either AL or AA showed elevated levels of kidney lipid peroxidation during consecutive exposures. However, there was also evidence of elevated levels of GPx, SOD, and CAT activity in the kidneys, which may have protected against lipid peroxidation and preserved renal function. Nevertheless, the observed antioxidant activity proved to be insufficient for the prevention of glomerular edema.