Amelioration of acetic acid-induced ulcerative colitis in rats by cetirizine and loratadine via regulation of the PI3K/Akt/Nrf2 signalling pathway and pro-inflammatory cytokine release

Objective(s): Ulcerative colitis is a chronic inflammatory bowel disease (IBD) that causes inflammation and ulcers in the rectum and the innermost layer of the large intestine. Our study aimed to elucidate the ameliorative effect of cetirizine (CTZ) and loratadine (LOR) against acetic acid-induced ulcerative colitis in rats via assessment of the PI3K/p-Akt/Nrf2 signaling pathway and proinflammatory cytokine release. Materials and Methods: Thirty-two rats were allocated into four groups (n=8). Group (I) was considered normal control. Acetic acid (AA) was injected intrarectally in groups (2-4). Group (2) was kept untreated. Group (3) was administered CTZ (20 mg/kg/day) for 7 days. Group (4) was administered LOR (10 mg/kg/day) for 7 days. Results: AA showed severe macroscopic colonic lesions associated with increased ulcer number, area, and severity with significantly elevated PI3K, p-Akt, Nrf2, TNF-alpha, and IL-6 in colorectal tissue as compared to the normal control group. All the aforementioned indicators were greatly improved by CTZ and LOR therapy. Conclusion: This is the first study to elucidate the ameliorative effect of CTZ and LOR against AA-induced UC in rats. CTZ and LOR treatment mitigates UC via amelioration of the PI3K/p-Akt/Nrf2 pathway and proinflammatory cytokine release.