Sarmiento-Ortega Victor Enrique, Moroni-González Diana, Diaz Alfonso, Brambila Eduardo, Treviño Samuel
Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Chemistry Department, Meritorious Autonomous University of Puebla, 14 Sur. FCQ1, Ciudad Universitaria, 72560, Puebla, C.P, Mexico.
Department of Pharmacy, Faculty of Chemistry Science, Meritorious Autonomous University of Puebla, 22 South. FCQ9, Ciudad Universitaria, 72560, Puebla, C.P, Mexico.
Biol Trace Elem Res. 2025 Apr;203(4):2382-2393. doi: 10.1007/s12011-024-04314-1. Epub 2024 Aug 6.
Cadmium (Cd) is a global pollutant, and its accumulation in the liver causes oxidative stress, inflammation, insulin resistance (IR), and metabolic complications. This study investigated whether curcumin treatment could alleviate hepatic IR in Wistar rats exposed to sub-chronic cadmium and explored the underlying molecular pathways. Male Wistar rats were divided into a control group (standard normocaloric diet + cadmium-free water) and a cadmium group (standard normocaloric diet + drinking water with 32.5 ppm CdCl) for 30 days. Oral glucose tolerance, insulin response, and IR were assessed using mathematical models. Liver tissue was analyzed for markers of oxidative stress, inflammation, and key regulatory pathways, including NF-κB, Nrf2, MAPKs (JNK and p38), and the IRS1-Akt pathway. We established an effective curcumin dose of 250 mg/kg for 5 days orally. Results demonstrated that after 30 days of exposure, cadmium accumulated in the liver, inducing an oxidative and inflammatory state. This was characterized by increased expression of NF-κB, JNK, and p38, along with diminished Nrf2 expression, hepatic IR, hyperglycemia, and hyperinsulinemia. Curcumin treatment effectively alleviated these metabolic disorders by restoring the balance between NF-κB and Nrf2 in the liver, modulating the MAPK pathway, and, consequently, improving oxidative and inflammatory balance. In conclusion, this study suggests that cadmium induces hepatic IR through an imbalance between NF-κB and Nrf2 signaling pathways. Curcumin treatment appears to improve these pathways, thereby ameliorating hepatic IR.
镉（Cd）是一种全球性污染物，其在肝脏中的蓄积会导致氧化应激、炎症、胰岛素抵抗（IR）和代谢并发症。本研究调查了姜黄素治疗是否能减轻亚慢性镉暴露的Wistar大鼠的肝脏IR，并探索其潜在的分子途径。将雄性Wistar大鼠分为对照组（标准正常热量饮食 + 无镉水）和镉组（标准正常热量饮食 + 含32.5 ppm CdCl的饮用水），持续30天。使用数学模型评估口服葡萄糖耐量、胰岛素反应和IR。分析肝脏组织中的氧化应激、炎症标志物以及关键调节途径，包括NF-κB、Nrf2、丝裂原活化蛋白激酶（JNK和p38）和IRS1-Akt途径。我们确定了口服5天的有效姜黄素剂量为250 mg/kg。结果表明，暴露30天后，镉在肝脏中蓄积，诱导氧化和炎症状态。其特征为NF-κB、JNK和p38表达增加，同时Nrf2表达减少、肝脏IR、高血糖和高胰岛素血症。姜黄素治疗通过恢复肝脏中NF-κB和Nrf2之间的平衡、调节丝裂原活化蛋白激酶途径，从而有效减轻这些代谢紊乱，进而改善氧化和炎症平衡。总之，本研究表明镉通过NF-κB和Nrf2信号通路之间的失衡诱导肝脏IR。姜黄素治疗似乎改善了这些途径，从而改善肝脏IR。
