Chloroquine Delays Healing of Acetic Acid-Induced Mucosal Damage in the Rat Stomach

Abstract

Chloroquine (CQ) is a 4-aminoquinoline derivative, most widely used in treating malaria. Although previous studies have reported the gastric acid enhancing and pro ulcerogenic effect of CQ, its role in resolution of gastric injury is relatively unknown. In this study, the effect of CQ on acetic acid induced gastric ulceration was investigated. Chronic gastric ulcers were induced in male Wistar rats by serosal application of acetic acid for 60 seconds. Subsequently, the animals were given either 0.1ml normal saline (Group B) or 3mg/kg Chloroquine sulphate (Group C) for three days starting 24 hours after ulcer induction. A control (sham-operated) group of animals (Group A) did not have any ulcer induced. The animals were sacrificed by days 7, 14 and 21 post ulceration for gastric ulcer score. Homogenised gastric tissues were also analysed colorimetrically for malodialdehyde (MDA) estimation. In another study, basal and stimulated gastric acid secretion was measured using the continuous perfusion technique, after which small sections of the gastric tissue were fixed in formalin for histological evaluation. Statistical analysis was by ANOVA and Bonferoni post-hoc test at p-0.05. Acetic acid produced visible and measurable ulcers in all animals in groups B and C while no visible ulcers were seen in the unulcerated control rats. Ulcer diameter and ulcer index were significantly increased in the Chloroquine-treated group on the 7th, 14th and 21st day post-ulcer induction. Reduction in ulcer diameter (noticeable in all the animals by day 21) was significantly reduced in the chloroquine treated rats. These observations were confirmed by results from microscopy. Compared with the control, basal gastric acid secretion was increased by chloroquine but decreased with days after ulcer induction. There was no significant increase in the percentage change of the histamine stimulated gastric acid secretion between the control and chloroquine treated groups (12.5%, and 15.52%) compared with the basal gastric acid secretion (45.34% and 24.55%) on days 14 and 21 respectively. It is concluded that chloroquine prolongs the natural healing of acetic acid induced ulcer in Wistar rat.