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 the study was to establish the effects of Artesunate-Amodiaquine and Artemether-Lumefantrine on gastric ulcers, malondialdehyde (MDA), reduced glutathione (GSH) and identify major histological changes in male Wistar rats. Gastric ulcers were induced using Indomethacin in four groups and group 1 was administered Artesunate, group 2 received Artesunate-Amodiaquine, group 3 received Artemether-Lumefantrine, and group 4 was a positive control (normal saline). Group five 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 apoptosis. Findings in this study demonstrate a new to revisit information on the pharmacodynamics of major circulating antimalarial agents in developing countries.

Artemisinin and l‐carnitine combination therapy alters the erythrocytes redox status

“…Intramuscular administration of 2 mg/kg artesunate into rats with experimental gastric ulcers did not alter the amount of MDA and GSH in gastric tissue. However, oral administration of artesunate‐amodiaquine (4–10 mg/kg) and artemether‐lumefantrine (2.3–27.4 mg/kg) increased the MDA and reduced GSH levels in gastric tissue (Kalange et al, 2020). In the present study, administration of a therapeutic dose (50 mg/kg) of ART for 1 week had no significant effect on CAT and POX activity and GSH level in the mice erythrocytes.…”