镉（Cd）是重金属镉产生胰腺炎的严重影响，而炎症和氧化应激（OS）与Cd诱导的胰腺损伤相关。本研究评估了褪黑激素受体激动剂玻璃酮胺（AGM）对Cd诱导的急性胰腺炎（AP）的影响，指出其对炎症、OS和Nrf2/HO-1途径的调节作用。大鼠口服AGM 14天，并在第7天注射氯化镉（CdCl2）。Cd增加了血清淀粉酶和脂肪酶，并导致胰腺内分泌和外分泌组织损伤。丙二醛（MDA）、一氧化氮（NO）和髓过氧化物酶（MPO）升高，核因子（NF）-kB p65、诱导型一氧化氮合酶（iNOS）、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α和CD40上调，抗氧化剂在Cd处理的大鼠胰腺中减少。AGM改善了血清淀粉酶和脂肪酶以及胰腺OS，NF-kB p65、CD40、炎症介质和caspase-3的调节，预防组织损伤并增强抗氧化剂。AGM下调了Keap1并增强了胰腺Cd处理的Nrf2和HO-1。体外研究结果显示AGM与Keap1、HO-1、CD40L和caspase-3之间的结合亲和性。总之，AGM通过预防炎症、OS和细胞凋亡以及调节Nrf2/HO-1途径来保护胰腺免受Cd诱导的AP的损伤。版权所有 © 2023 Elsevier B.V. 保留所有权利。

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.Copyright © 2023 Elsevier B.V. All rights reserved.