Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation

• Published in: Canadian journal of physiology and pharmacology 2022-02, Vol.100 (2), p.176-183
• Main Authors: Mohamed, Mervat Z, Mohammed, Hanaa H, Khalaf, Hanaa M
• Format: Article
• Language: English
• Subjects: acute pancreatitis; Amylases - blood; Animal models; Animals; Anti-Inflammatory Agents; Antihistamines; Arginine; Arginine - adverse effects; Caspase 3 - genetics; Caspase 3 - metabolism; Caspase-3; Cyproheptadine - administration & dosage; Cyproheptadine - analogs & derivatives; Cyproheptadine - pharmacology; Cyproheptadine - therapeutic use; Cytokines; Dosage and administration; Drug therapy; Gene Expression - drug effects; Health aspects; Histamine; Histamine Antagonists; Histamine receptors; Inflammation; Inflammation Mediators - metabolism; Inflammatory diseases; Injection; l; Male; Morbidity; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Oxidative Stress - drug effects; PAF; Pancreas; Pancreatitis; Pancreatitis - chemically induced; Pancreatitis - drug therapy; pancréatite aiguë; Peroxidase; Physiological aspects; Platelet activating factor; Rats; Rats, Wistar; Rodents; rupatadine
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2021-0330

Acute pancreatitis (AP) is an abrupt inflammatory disorder causing high morbidity and mortality. As AP is an insidious medical emergency, a curative modality is required instead of a preventive measure. Thus, we investigated the possible curative effect of rupatadine on a rat model of AP. Rupatadine is a potent histamine receptor 1 (H1R) and platelet-activating factor (PAF) blocker. We used four groups of six Wistar rats as follows: the control group received vehicle; the rupatadine control group received rupatadine as 6 mg/kg orally; the AP group received l- arginine intraperitoneally, and the treatment group received rupatadine at 1, 6, and 24 h after l- arginine injection. The levels of serum amylase, pancreatic oxidative parameters, and pancreatic cytokines were measured. PAF, histamine, and myeloperoxidase levels were determined in the pancreas. Histopathological and immunohistochemical examinations were performed to determine nuclear factor kappa-B (NF-κB) and caspase 3 expressions. Oxidative damage and severe inflammation were detected in the pancreas of the AP group. Rupatadine reduced the oxidative damage and the levels of proinflammatory cytokines, PAF, histamine, myeloperoxidase, NF-κB, and caspase 3 expressions. It restored the pancreatic acini to almost normal condition. Rupatadine induced important anti-inflammatory and antiapoptotic effects against l- arginine-induced AP.