Mostafalou Sara, Moafi-Madani Fatemeh, Baeeri Maryam, Rahimifard Mahban, Haghi-Aminjan Hamed
Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran.
Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2025;28(6):784-789. doi: 10.22038/ijbms.2025.84651.18311.
Arsenic is classified as a toxic metal that is naturally found in the Earth's crust, and long-term exposure to it can result in chronic human disorders like cancer and diabetes. Azelaic acid (AZA), a natural dicarboxylic acid, has been reported to have anti-oxidant and anti-inflammatory effects; hence, it may protect against the metabolic toxicity of arsenic. This study aimed to investigate whether AZA could ameliorate sodium arsenite (SA) toxicity toward rat islets of Langerhans.
Pancreatic Islets of Langerhans isolated from adult male Wistar rats were divided into four groups of 10: control, SA, AZA, and SA plus AZA. Twenty-four hours after incubation, cell viability, cell death pathways, reactive oxygen species (ROS), inflammatory factor gene expression, and insulin secretion were evaluated.
SA dose-dependently decreased cell viability, increased apoptosis, ROS generation, expression of inflammatory mediators (NF-κB, IL-1β, and TNF-α), and insulin secretion. AZA was able to ameliorate all these changes significantly.
Our results indicate that SA can potentially disrupt cellular homeostasis and function in the islets of Langerhans and can increase the risk of metabolic diseases such as diabetes. On the other hand, AZA protected islets of Langerhans against the toxic effects of SA, seemingly due to its anti-apoptotic, anti-inflammatory, and anti-oxidant properties, indicating that AZA may have the potential to run intracellular mechanisms beneficial for coping with the metabolic toxicity of arsenic.
砷被归类为一种在地壳中天然存在的有毒金属，长期接触砷会导致人类慢性疾病，如癌症和糖尿病。壬二酸（AZA）是一种天然二羧酸，据报道具有抗氧化和抗炎作用；因此，它可能预防砷的代谢毒性。本研究旨在调查AZA是否能改善亚砷酸钠（SA）对大鼠胰岛的毒性。
从成年雄性Wistar大鼠分离的胰岛被分为四组，每组10个：对照组、SA组、AZA组和SA加AZA组。孵育24小时后，评估细胞活力、细胞死亡途径、活性氧（ROS）、炎症因子基因表达和胰岛素分泌。
SA剂量依赖性地降低细胞活力，增加细胞凋亡、ROS生成、炎症介质（NF-κB、IL-1β和TNF-α）的表达以及胰岛素分泌。AZA能够显著改善所有这些变化。
我们的结果表明，SA可能会破坏胰岛细胞的内环境稳定和功能，并增加患糖尿病等代谢疾病的风险。另一方面，AZA保护胰岛免受SA的毒性作用，这似乎归因于其抗凋亡、抗炎和抗氧化特性，表明AZA可能具有运行有益于应对砷代谢毒性的细胞内机制的潜力。
