Abstract
ObjectiveAntimalarials 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.ResultsAntimalarial 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.
Highlights
Antimalarial single therapies (AMTs) are the aminoquinoline and artemisinin derivatives and artemisinin-based combination therapies and the development of resistance against them is a major public health threat especiallyKalange et al BMC Res Notes (2020) 13:230 artemisinin, are generally safer with limited side effects [6]
Antimalarial combination therapies were associated with a high gastric ulcer index than a single antimalarial agent, Artesunate
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
Summary
Effects of Artesunate‐amodiaquine treatment on gastric ulcer index, oxidative and antioxidant status The study showed that the ulcer index was relatively the same in all experimental animals except in the positive control (P < 0.05). Ulcer index was higher in the Artesunate-amodiaquine than Artemether-lumefantrine groups no significant differences were observed (Fig. 1a). Malondialdehyde (MDA) levels were highest in the combination groups (P > 0.05) with significantly high concentrations observed in the antimalarial combinations and Artesunate (Fig. 1b). MDA levels were lower in the negative control and no significant differences were observed with Artesunate (P > 0.05). Combination therapies of antimalarials i.e. Artesunate-amodiaquine and Artemetherlumefantrine were associated with diffuse vacuolations in the non-glandular stomach and acute inflammation in the glandular stomach showing that pathological lesions are widespread in the gastric mucosa.
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