Effects of artemisinin, with or without lumefantrine and amodiaquine on gastric ulcer healing in rat

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.

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

“…1). Findings in this study demonstrate the safety of Artesunate and this was in agreement with previous studies [8,9,40]. This offers a firm basis for their safety [6].…”

“…This dosage was chosen since 2 mg/kg was very safe in subchronic studies of Artesunate ranging from 2 to 10 mg/kg [38,39]. Artesunate-Amodiaquine per os at 4/10 mg/kg p.o in the form Winthrop ® was used since this had previously been reported to have effects on gastric mucosa [40] while Artemether-Lumefantrine (2.3/27.4 mg/kg) from Combiart ® was administered as a follow up on a previously used dosage of artemetherlumefantrine (2/12 mg/kg) on gastric ulcers [40]. The positive control (with ulcers) was treated with normal saline at 1 ml/kg p.o.…”

Research Advances on Health Effects of Edible Artemisia Species and Some Sesquiterpene Lactones Constituents

“…They have also shown efficacy on several cancer lines, along with anti-inflammatory activity, modulating the immune response by regulating cell proliferation and cytokine release [191][192][193]. They also have anti-ulcerous [194], antinociceptive [195], antiviral [196], antifungal [180], and antibacterial [197] activities, besides being effective in other disorders such as respiratory [198], and related to metabolic syndromes, including obesity, diabetes and atherosclerosis [199,200], being many of the effects mentioned evaluated in in vivo models…”