Antimalarial combination therapies increase gastric ulcers through an imbalance of basic antioxidative-oxidative enzymes in male Wistar rats

Abstract

Objective: Antimalarials are globally used against plasmodium infections, however, information on the safety of new antimalarial combination therapies on the gastric mucosa is scarce. The aim of this study was to investigate the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on ulcer induction. Malondialdehyde (MDA), reduced glutathione (GSH) and major histological changes in male Wistar rats following ulcer induction using Indomethacin were investigated. Gastric ulcers were in four groups; Group I was administered Artesunate, group II received Artesunate-Amodiaquine, group III received Artemether-Lumefantrine, and group IV was a positive control (normal saline). Group V was the negative control consisting of healthy rats. Results: Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate. In addition, levels of MDA were significantly higher in the combination of therapies while levels of GSH were lower in comparison to Artesunate and the negative control. Microscopically, antimalarial combination therapies were associated with severe inflammation and tissue damage than Artesunate in the gastric mucosa showing that antimalarial combination therapies exert their toxic effects through oxidative stress mechanisms, and this leads to cellular damage. Findings in this study demonstrate a need to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.