Artesunate, with or without Mefloquine, alters activities of Mast cells, Anti-inflammatory markers and Antioxidants in Rats with Acetic acid induced Gastric ulcers

Abstract

Artemisinin-based antimalarial drugs have previously been shown to enhance healing of experimental gastric ulcers when compared with the delayed healing effect of the chloroquine and its derivatives. During inflammatory phase of gastric ulcer healing, mast cells maintain the gastric epithelium’s integrity. In this study the effects of some artemisinin-based antimalarial drugs on mast cells, anti-inflammatory markers and antioxidants activities during gastric ulcer healing was investigated. Male Wistar rats (140-170g, n=10) were divided into 5 groups. The control rats (Group 1) received normal saline and no ulcer was induced while in other groups, chronic gastric ulcers were induced using 60% acetic acid and treated accordingly for 7 days with normal saline (Group 2), Artesunate, 2mg/kg (Group 3), Artequine, 4mg/kg) (Group 4) and Zinc sulphate, 80mg/kg (Group 5). Bodyweight, haematological variables, ulcer score, gastric biochemical and histological analysis were assessed 3- and 7-days post ulceration. Data were analyzed using One-way ANOVA and Dunnette post-hoc tests at p < 0.05. Reduction in body weight was observed in animals 3 and 5 days after ulcer induction, though there was significant reversal of weight losses above the pre-ulcer values by day 7. Healing was evident in the stomach of all animals with acetic acid-induced ulcers. By day-7, the mean ulcer score in the normal saline-, Artequine- and Zinc sulphate-treated rats were 8.40 ± 0.35, 0.27± 0.27 and 0.33 ± 0.17 respectively. No visible ulcers were seen in the Artesunate treated group (100% healing rate). Neutrophil/lymphocyte ratio and gastric nitrite levels were significantly increased in the normal saline treated group 3 days after ulcer induction.  Platelet count was significantly increased in the antimalarial treated groups compared with the untreated group. There were delayed gastric ulcer healing and absence of mast cells at the ulcer site in the untreated group compared with the treated groups.  Artemisinin based-combination drug exhibit enhanced healing of experimental gastric ulcer healing through regulated activities of mast cells and endogenous anti-oxidative mechanisms