The Effect of Histamine H4 Receptor Antagonist JNJ7777120 on Experimental Ulcer Models in Rats

Abstract

Objective: Gastric ulcer, one of the common diseases of the gastrointestinal system, affects more than 5% of the population of the world. Gastric ulcer occurs when the balance between mucosal damage mechanisms and mucosal protection mechanisms is disrupted. Helicobacter pylori infection, alcohol use, nonsteroidal anti-inflammatory drugs (NSAIDs), and stress are among the most common causes of gastric ulcers. Factors such as disruption of microcirculation, decreased mucus production, inhibition of gastric mucosal prostaglandin synthesis, and gastric acidity are involved in the pathogenesis of ulcers. It has been suggested that histamine H4 receptors, mostly found on mast cells, dendritic cells, basophils, eosinophils, and T cells, are principally responsible for inflammatory reactions. This study aims to investigate the gastroprotective effect of the H4 receptor antagonist, JNJ7777120 (JNJ), on experimental ulcer models. Methods: In this study, the possible protective effects of JNJ (10 mg/kg s.c.) were investigated by creating experimental ulcer models with indomethacin (40 mg/kg i.g.), ethanol (1 ml 96% i.g.), and lipopolysaccharide (LPS) (1 mg/kg/day, i.p. for 3 days) in Sprague Dawley rats. Macroscopic scoring, histopathological examinations, and biochemical analyses were performed on the stomach samples obtained to evaluate the protective effect of JNJ. Ulcer index and levels of COX-1, SOD, NF-κB, TNF-α, catalase, and caspase were measured. Results: In ethanol- and indomethacin-induced ulcer groups, JNJ treatment was found to significantly reduce ulcer formation in the stomach. In the groups treated with LPS, gastric damage, and gastritis occurred, but the preventive effect of JNJ on ulcer formation was not determined. Conclusion: JNJ has a gastroprotective effect for ulcers. In future studies, it will be useful to test different doses to investigate the protective effect of JNJ on gastric damage caused by LPS.