• Zahraa A Baydoun, Muddanna Rao, and Islam Khan.
• Med Princ Pract. 2024 Nov 4: 1221-22.

ObjectivesInflammatory bowel diseases which are characterized by endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling pathway, are commonly treated with 5-amino salicylic acid (5-ASA). The objective of this study was to investigate the role of 5-amino salicylic acid in the UPR-signaling pathway in experimental colitis.Materials And MethodsColitis was induced in male Sprague-Dawley rats by intrarectal instillation of trinitrobenzene sulfonic acid. Animals received 5-amino salicylic acid (100 mg/kg body weight) two hours before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis.ResultsThe expression of protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK), a mediator of UPR-signaling increased significantly (p < 0.05), while inositol requiring enzyme type-1 (IRE1) and the CCAAT/enhancer-binding homologous protein (CHOP) remained unaltered in the inflamed colon. The expression of glucose regulated protein-78, activator of transcription factor-4 and phosphorylated eukaryotic initiation factor-2α (eIF2αP) increased (p < 0.05) in the inflamed colon. However, the levels of eIF2α protein and mRNA expression remained unchanged. Myeloperoxidase activity, colon weight and infiltration of inflammatory cells increased significantly (p < 0.05) in the submucosa whereas the body weight decreased. These changes were significantly inhibited by 5-amino salicylate treatment.ConclusionThese findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway.The Author(s). Published by S. Karger AG, Basel.

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