Mitigation of Indomethacin-Induced Gastric Ulcer in Rats by 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline: Modulation of Inflammatory Mechanisms

Objective: To investigate the gastroprotective influence of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline in a rat model of indomethacininducedgastric ulcers. Methods: Thirty male Wistar rats were randomly divided into five groups (n = 6) as follows: Group 1 (control), Group 2 (indomethacin only, 30 mg/kg), Group 3 (indomethacin and 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline, 30 mg/kg), Group 4 (indomethacin with 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline, 60 mg/kg), and Group 5 (indomethacin with esomeprazole, 30 mg/kg). The efficacy of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline in mitigating gastric ulcers induced by indomethacin in rats was evaluated based on gastric morphology, histopathology, and inflammatory biomarkers. Results: Indomethacin-induced stomach ulcers resulted in epithelial damage and blood streaks on the gastric mucosa. However, treatmentwith indomethacin and 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline (60 mg/kg) significantly (P < 0.05) reduced ulcers compared to the indomethacin-only group. Inflammatory cells were observed in the indomethacin group, while the 60 mg/kg 2,3-Dichloro-6- (trifluoromethoxy) quinoxaline-treated group exhibited the restoration of normal epithelial tissue and minimal inflammatory cells, similar to the control and esomeprazole-treated groups. Furthermore, 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline significantly decreased inflammatory biomarkers (TNF-α, IL-6, INF-γ, and IL-β1) and increased gastroprotective mediator levels (PGE2 and mucin), both with P-values below 0.05, in contrast to the effects of indomethacin. Conclusion: This study provides clinical evidence highlighting the gastroprotective properties of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline. Its initial application reveals, for the first time, its efficacy in treating gastric ulcers induced by indomethacin. However, further tests are warranted to validate these findings.