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

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.

The influence of risk factors in recurrent peptic ulcer hemorrhage

Gastrointestinal hemorrhage is one of the most frequent complications that occurs in 15 20% patients with peptic ulcer disease. Recurrent ulcer hemorrhage presents in the first 72 hours after initial bleeding; they are the most important cause of death. The aim of our study was to show the possibility of ulcer recurrent hemorrhage combined with risk factors: age 60, high risk lesion (active arterial bleeding, visible blood vessel, adherent coagulum), the size, ulcer base and localization (posterior duodenal wall, lesser curvature or high gastric ulcer), commorbidities (cardiovascular and liver diseases) and haemodynamic instabilities. The combination of these risk-factors unproportionally increases the risk: presence of two risk factors gives the possibility of recurrent bleeding of 16.67%, three risk factors 58.82%, four 93.33%, while the presence of five risk factors shows 100 % possibility. Probability of death is 8.27 times greater if ulcer hemorrhage occurs.