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.

Antioxidant potential of resveratrol on plasmodium berghei-induced malaria in diabetic male Wistar rats

“…The MDA level in the artesunate group was reasonably higher than that of other groups, except resveratrol 100mg/kg group and normal controls. This nding agrees with the results obtained studies by [38] and [39] that artesunate exerts toxic effect via oxidative stress mechanism, which leads to cellular damage.…”

The Effects of Apocynin on Monosodium Glutamate Induced Liver Damage of Rats

“…After decapitation liver tissue samples were washed with phosphate-buffered saline (PBS). 10% tissue homogenate was prepared by homogenising with a cold 150 mM KCl solution [ [23] , [24] , [25] ]. Malondialdehyde (MDA) levels were analysed using Ohkawa et al methods [ 26 ].…”

Prevalence and control of Malaria in Pregnant Antenatal Mothers at Main Hospital, Iganga District, Eastern Uganda.

“…Therefore malaria is one of the most important diseases in Uganda, causing significant morbidity, mortality and negative socio-economic impact. Malaria is responsible for 30-50% of outpatient visits and 35% of admissions [20][21][22][23][24]. Pregnancy exacerbates malaria through a non-specific activity of immune system, the protective antiplasmodial activity is suppressed at pregnancy and this has a clinical consequence [5, 25, and 26].…”