Abstract
Background
Antimalarial drugs have been shown to predispose the stomach to ulceration in rats. However, their role in the modulation of gastric ulcer healing is not known. The aim of the present study is to investigate the effect of artemisinin-based combination therapies on ulcer healing.
Methods
Gastric kissing ulcers were induced in 40 male albino rats (150–180 g) using 0.2 mL 50% acetic acid. One day after the ulcer induction, experimental rats were divided into four groups and treated once daily orally for 3 days as follows: (1) normal saline, (2) artemether-lumefantrine (2/12 mg/kg), (3) artesunate-amodiaquine (4/10 mg/kg), and (4) artesunate (2 mg/kg) only. A fifth group of 10 rats served as overall control with no ulcer induced and no treatment given. Ulcer healing was determined on days 4 and 7 post induction using ulcer score and planimetry.
Results
Artesunate decreased ulcer severity by 12.5% and 52.0% on days 4 and 7, respectively. Significant increases in severity were observed in rats treated with artemether-lumefantrine (25.0% and 40.0%) and artesunate-amodiaquine (50.0% and 95.0%). Lipid peroxidation was decreased by artesunate by day 7 (27%; p<0.05) but increased in artemether-lumefantrine and artesunate-amodiaquine administered rats (63.6% and 55%; p<0.05). The activity of superoxide dismutase was reduced by artesunate-amodiaquine on day 7 (22%; p<0.05) but no effect in the artemether-lumefantrine treatment. Neutrophil infiltration, total leukocyte count, neutrophil-lymphocyte ratio, and C-reactive protein values were significantly increased in the artemether-lumefantrine and artesunate-amodiaquine treated groups when compared with the untreated ulcer control group (p<0.05). These variables were all reduced by artesunate (p<0.05).
Conclusions
This study revealed that although artesunate may be beneficial in gastric ulcer healing, its combination with either lumefantrine or amodiaquine may delay healing of gastric mucosal injury.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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