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

• Published in: International immunopharmacology Vol. 124; p. 110833
• Main Authors: Alruhaimi, Reem S., Hassanein, Emad H.M., Abd El-Aziz, Mostafa K., Siddiq Abduh, Maisa, Bin-Ammar, Albandari, Kamel, Emadeldin M., Mahmoud, Ayman M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-11-2023
• Subjects: Heavy metals; Inflammation; Oxidative stress; Pancreatitis; Oxidative stress; Inflammation; Heavy metals; Pancreatitis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.110833

•Acute pancreatitis is a serious effect of exposure to cadmium.•Cadmium induces oxidative stress and upregulates NF-Kb and CD40 in rat pancreas.•Agomelatine ameliorates cadmium-induced acute pancreatitis and oxidative stress.•Agomelatine prevents cadmium-induced pancreatic tissue injury.•Agomelatine upregulates pancreatic Nrf2/HO-1 signaling in cadmium-administered rats.
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.