Endoplasmic Reticular Stress and Pathogenesis of Experimental Colitis: Mechanism of Action of 5-Amino Salicylic Acid
Year: 2024
Type: article
Abstract: OBJECTIVES: Inflammatory 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 METHODS: Colitis 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) 2 h before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis. RESULTS: The expression of protein kinase R (PKR)-like 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. CONCLUSION: These findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway. OBJECTIVES: Inflammatory 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 METHODS: Colitis 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) 2 h before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis. RESULTS: The expression of protein kinase R (PKR)-like 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. CONCLUSION: These findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway.
Source: Medical Principles and Practice
DOI: 10.1159/000541791
Authors: Zahraa A. Baydoun, Muddanna Rao, Islam Khan
Institution: Kuwait University
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4404038858