Maqbool Faheem, Bahadar Haji, Niaz Kamal, Baeeri Maryam, Rahimifard Mahban, Navaei-Nigjeh Mona, Ghasemi-Niri Seyedeh Farnaz, Abdollahi Mohammad
International Campus, Tehran University of Medical Sciences (TUMS-IC), Tehran, Iran; Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
Department of Pharmacy, Kohat University of Science and Technology, Kohat, 26000, Pakistan.
Food Chem Toxicol. 2016 Jul;93:119-28. doi: 10.1016/j.fct.2016.05.005. Epub 2016 May 10.
Mercury (Hg) is a well-known heavy metal and causes various toxic effects. It is abundantly present in fish in the form of methyl mercury (MeHg). Also, various other forms of mercury can enter human body either from environment like inhalation or through dental amalgams. The present study was designed to assess MeHg induced toxicity in mouse plasma and pancreatic islets with respect to insulin secretion, oxidative balance, glucose tolerance, gene expression, caspases 3 and 9 activities. MeHg was dissolved in tap water and administered at doses 2.5, 5 and 10 mg/kg/day, for 4 weeks. In mice, MeHg significantly caused increase in plasma insulin as well as C-peptides. Glucose intolerance, insulin resistance and hyperglycemia are main consequences of our study that correlate with the gene expression changes of glucose homeostasis as well. MeHg caused increase lipid peroxidation in a dose-dependent manner in plasma as well as pancreatic islets. In addition, total thiol molecules and ferrous reducing antioxidant power in MeHg treated group was decreased in plasma as well as pancreatic islets. Caspases 3 and 9 activities of pancreatic islets were upregulated in MeHg exposed animals. Reactive oxygen species were extremely high in pancreatic islets of MeHg treated groups. MeHg disrupted gluconeogenesis/glycogenolysis pathways and insulin secretory functions of islets by targeting GDH, GLUT2 and GCK genes of pancreatic islets. In conclusion, the current study revealed that insulin pathways, oxidative balance and glucose metabolism encoded genetic makeup are susceptible to MeHg toxicity and the subsequent oxidative stress and alternations in gene expression could lead toward functional abnormalities in other organs.
汞（Hg）是一种众所周知的重金属，会造成各种毒性影响。它以甲基汞（MeHg）的形式大量存在于鱼类中。此外，各种其他形式的汞可通过吸入等环境途径或通过牙科汞合金进入人体。本研究旨在评估甲基汞对小鼠血浆和胰岛的毒性，涉及胰岛素分泌、氧化平衡、葡萄糖耐量、基因表达、半胱天冬酶3和9的活性。将甲基汞溶解于自来水中，以2.5、5和10毫克/千克/天的剂量给药，持续4周。在小鼠中，甲基汞显著导致血浆胰岛素以及C肽增加。葡萄糖不耐受、胰岛素抵抗和高血糖是我们研究的主要结果，这也与葡萄糖稳态的基因表达变化相关。甲基汞在血浆和胰岛中均以剂量依赖性方式导致脂质过氧化增加。此外，甲基汞处理组血浆和胰岛中的总硫醇分子和亚铁还原抗氧化能力均降低。在暴露于甲基汞的动物中，胰岛的半胱天冬酶3和9活性上调。甲基汞处理组的胰岛中活性氧极高。甲基汞通过靶向胰岛的GDH、GLUT2和GCK基因破坏糖异生/糖原分解途径和胰岛的胰岛素分泌功能。总之，当前研究表明胰岛素途径、氧化平衡和葡萄糖代谢编码的基因组成易受甲基汞毒性影响，随后的氧化应激和基因表达改变可能导致其他器官的功能异常。
