Journal of Inflammation Research (Mar 2024)
Gastroprotective Effect of 2,3-Dimethylquinoxaline Against Indomethacin-Induced Gastric Ulcer in Rat
Abstract
Abdelbagi Alfadil1,2 1Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 2Center of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Abdelbagi Alfadil, Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, Jeddah, 21589, Saudi Arabia, Tel +96612 6952000 Ext:21062, Email [email protected]: Gastric ulcers pose a significant health risk due to an imbalance between protective and aggressive factors on the mucous membrane. Nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage affects 25% of users. Quinoxaline compounds, known for their diverse biological properties, have potential applications in cancer therapy and as antimicrobial agents targeting various pathogens.Objective: Our study aimed to investigate the impact of DMQ on gastroprotective mechanisms in an experimental model of indomethacin-induced gastric ulcer.Methods: Thirty male Wistar rats were randomly assigned to five groups. Group 1 served as the control, while Group 2 received a single oral dose of IND (30 mg/kg). Groups 3 and 4 received oral DMQ (30 mg/kg and 60 mg/kg, respectively) for three days, with the final dose administered intragastrically one hour before IND administration. Group 5 received esomeprazole (30 mg/kg) orally for three days, with the final dose given one hour before IND administration. Rats were sacrificed four hours after IND induction.Results: Indomethacin-induced ulcers were associated with epithelial damage and blood streaks on the gastric mucosa. However, DMQ significantly decreased levels of inflammatory biomarkers (TNF-α, IL-6, Cox-2, IFN-γ, and IL-β 1) while increasing gastroprotective mediator prostaglandin E2 (PGE2) and mucin levels. Histopathological analysis revealed a significant reduction in ulcer-induced pathological alterations and upregulation of tumor suppressor genes (NF-κB levels) following DMQ treatment. Rats treated with Indo+DMQ showed a significant decrease in ulcer index compared to the Indo group, with mild injuries observed.Conclusion: DMQ demonstrated promising gastroprotective effects against IND-induced gastric ulcers, as evidenced by alterations in histopathological data and upregulation of gene expression.Keywords: 2,3-dimethylquinoxaline, indomethacin, gastric ulcer, inflammatory biomarkers
