Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
J Biochem Mol Toxicol. 2019 Sep;33(9):e22368. doi: 10.1002/jbt.22368. Epub 2019 Jul 23.
Exposure to arsenic has been linked to the development of type 2 diabetes though its mechanism of toxicity remains unresolved. In this study berberine (BBR) effects on arsenic-induced sirtuin 3 (Sirt3) modifications in isolated mitochondria from rat pancreas were evaluated and compared with metformin (MET). With arsenic, mitochondrial reactive oxygen species (ROS), oxidative stress, and insulin resistance were obtained higher than control. From our results and in the presence of arsenic trioxide, insulin resistance and Sirt3 levels were found to be predominantly elevated that could be the result of compensating mechanisms. Apparently, BBR and MET recruit both direct (as an antioxidant) and indirect mechanisms (Sirt3 content) to deal with arsenic trioxide toxicity. Metformin compared with BBR exhibited a less significant effect on ROS levels and since its direct antioxidant property is minor, depressed the ROS level mainly through the Sirt3 modification.
砷暴露与 2 型糖尿病的发生有关，但其毒性机制仍未解决。在这项研究中，评估了黄连素（BBR）对大鼠胰腺分离线粒体中砷诱导的沉默调节蛋白 3（Sirt3）修饰的影响，并与二甲双胍（MET）进行了比较。与砷相比，线粒体活性氧（ROS）、氧化应激和胰岛素抵抗均高于对照组。根据我们的结果，在三氧化二砷存在的情况下，发现胰岛素抵抗和 Sirt3 水平明显升高，这可能是补偿机制的结果。显然，BBR 和 MET 既采用直接（作为抗氧化剂）机制，也采用间接机制（Sirt3 含量）来应对三氧化二砷毒性。与 BBR 相比，MET 对 ROS 水平的影响较小，由于其直接抗氧化作用较小，主要通过 Sirt3 修饰来降低 ROS 水平。
