Artemether-Lumefantrine treatment combined with albendazole and ivermectin induced genotoxicity and hepatotoxicity through oxidative stress in Wistar rats

Abstract

Mass drug administration against malaria and parasitic worm co-infections is capable of increasing health risk. This study investigated the hepatotoxicity, genotoxicity and oxidative stress induced by combinations of Arthemether-Lumefantrine (A-L) with Albendazole (ABZ) and Ivermectin (IVR) treatments in rats. 65 rats equally distributed into 13 groups were orally gavaged human therapeutic doses (×1.0), half of the doses (×0.5) and twice the doses (×2.0) of these drugs per body weights. Blood, liver and bone marrow cells were analyzed for serum biochemistry, histopathology and micronucleated polychromatic erythrocytes (MNPCE) respectively. Treated rats showed clinical signs of toxicity. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and malondialdehyde (MDA) significantly increase with concomitant decrease in superoxide dismutase (SOD) and catalase (CAT) in the serum. Liver histology revealed single cell hepatocellular necrosis and kupffer cell hyperplasia, multiple foci vacuolar changes in the hepatocytes, thinning of hepatic cord and congestion of the sinusoids by inflammatory cells. Also, frequency of MNPCE significantly increased in the treated rats. The findings revealed that combine treatment of A-L with ABZ and IVR mostly at ×2.0 and ×1.0 induced liver dysfunctions and somatic mutations through oxidative stress in rats. These suggest health risk in wildlife and human populations during treatments with these drug combinations.