The melatonin receptor agonist agomelatine protects against acute pancreatitis induced by cadmium by attenuating inflammation and oxidative stress and modulating Nrf2/HO-1 pathway

Alruhaimi, Reem S, Hassanein, Emad HM, Abd El-Aziz, Mostafa K, Siddiq Abduh, Maisa, Bin-Ammar, Albandari, Kamel, Emadeldin M and Mahmoud, Ayman M (2023) The melatonin receptor agonist agomelatine protects against acute pancreatitis induced by cadmium by attenuating inflammation and oxidative stress and modulating Nrf2/HO-1 pathway. International Immunopharmacology, 124. 110833. ISSN 1567-5769

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Official URL: https://doi.org/10.1016/j.intimp.2023.110833

Abstract

Pancreatitis is a serious effect of the heavy metal cadmium (Cd) and inflammation and oxidative stress (OS) are implicated in Cd-induced pancreatic injury. This study evaluated the effect of the melatonin receptor agonist agomelatine (AGM) on Cd-induced acute pancreatitis (AP), pointing to its modulatory effect on inflammation, OS, and Nrf2/HO-1 pathway. Rats were supplemented with AGM orally for 14 days and a single injection of cadmium chloride (CdCl2) on day 7. Cd increased serum amylase and lipase and caused pancreatic endocrine and exocrine tissue injury. Malondialdehyde (MDA), nitric oxide (NO) and myeloperoxidase (MPO) were elevated, nuclear factor (NF)-kB p65, inducible NO synthase (iNOS), interleukin (IL)-6, tumor necrosis factor (TNF)-α and CD40 were upregulated, and antioxidants were decreased in the pancreas of Cd-administered rats. AGM ameliorated serum amylase and lipase and pancreatic OS, NF-kB p65, CD40, pro-inflammatory mediators and caspase-3, prevented tissue injury and enhanced antioxidants. AGM downregulated Keap1 and enhanced Nrf2 and HO-1 in the pancreas of Cd-administered rats. In silico findings revealed the binding affinity of AGM with Keap1, HO-1, CD40L and caspase-3. In conclusion, AGM protected against AP induced by Cd by preventing inflammation, OS and apoptosis and modulating Nrf2/HO-1 pathway.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	09 Nov 2023 14:41
Publisher:	Elsevier
Additional Information:	© 2023. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/(opens in new tab/window)
Divisions:	Faculties > Science and Engineering
Subject terms:	Heavy metals, Inflammation, Oxidative stress, Pancreatitis, 1115 Pharmacology and Pharmaceutical Sciences, Immunology
Data Access Statement:	The manuscript contains all data supporting the reported results.
URI:	https://e-space.mmu.ac.uk/id/eprint/633035
DOI:	https://doi.org/10.1016/j.intimp.2023.110833
ISSN	1567-5769
e-ISSN	1878-1705

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