title: Mercuric compounds induce pancreatic islets dysfunction and apoptosis in vivo.
abstract: Mercury is a toxic heavy metal that is an environmental and industrial pollutant throughout the world. Mercury exposure leads to many physiopathological injuries in mammals. However, the precise toxicological effects of mercury on pancreatic islets in vivo are still unclear. Here, we investigated whether mercuric compounds can induce dysfunction and damage in the pancreatic islets of mice, as well as the possible mechanisms involved in this process. Mice were treated with methyl mercuric chloride (MeHgCl, 2 mg/kg) and mercuric chloride (HgCl(2), 5 mg/kg) for more than 2 consecutive weeks. Our results showed that the blood glucose levels increased and plasma insulin secretions decreased in the mice as a consequence of their exposure. A significant number of TUNEL-positive cells were revealed in the islets of mice that were treated with mercury for 2 consecutive weeks, which was accompanied by changes in the expression of the mRNA of anti-apoptotic (Bcl-2, Mcl-1, and Mdm-2) and apoptotic (p53, caspase-3, and caspase-7) genes. Moreover, plasma malondialdehyde (MDA) levels increased significantly in the mice after treatment with mercuric compounds for 2 consecutive weeks, and the generation of reactive oxygen species (ROS) in the pancreatic islets also markedly increased. In addition, the mRNA expression of genes related to antioxidation, including Nrf2, GPx, and NQO1, were also significantly reduced in these islets. These results indicate that oxidative stress injuries that are induced by mercuric compounds can cause pancreatic islets dysfunction and apoptosis in vivo.
authors.affiliation: Department of Urology, China Medical University Hospital, and School of Medicine, China Medical University, No.2 Yuh-Der Rd., Taichung 404, Taiwan. cfhuang@mail.cmu.edu.tw.
authors.forename: Kuo-Liang
authors.initials: KL
authors.lastname: Chen
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Su
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Yen
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Kuan-I
authors.initials: KI
authors.lastname: Lee
authors.forename: Feng-Cheng
authors.initials: FC
authors.lastname: Tang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Tien-Hui
authors.initials: TH
authors.lastname: Lu
authors.forename: Yi-Chang
authors.initials: YC
authors.lastname: Su
authors.forename: Chun-Fa
authors.initials: CF
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008627:Mercuric Chloride / Q000737:chemistry / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008767:Methylmercury Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D008315:Malondialdehyde; D008627:Mercuric Chloride; D005979:Glutathione Peroxidase; D051736:Proto-Oncogene Proteins c-mdm2; D053148:Caspase 3; D053179:Caspase 7; C004925:methylmercuric chloride