Mercuric compounds induce pancreatic islets dysfunction and apoptosis in vivo
Journal
International Journal of Molecular Sciences
Journal Volume
13
Journal Issue
10
Pages
12349-12366
Date Issued
2012
Author(s)
Chen K.-L.
Liu S.-H.
Su C.-C.
Yen C.-C.
Lee K.
Tang F.-C.
Chen Y.-W.
Lu T.-H.
Su Y.-C.
Huang C.-F.
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 (HgCl2, 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. ? 2012 by the authors; licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
caspase 3; caspase 7; glucose; glutathione peroxidase; insulin; malonaldehyde; messenger RNA; methylmercuric chloride; protein bcl 2; protein mcl 1; protein MDM2; protein p53; reactive oxygen metabolite; transcription factor Nrf2; caspase 3; caspase 7; glucose blood level; glutathione peroxidase; insulin; malonaldehyde; mercuric chloride; methylmercuric chloride; methylmercury derivative; protein bcl 2; protein MDM2; protein p53; reactive oxygen metabolite; animal cell; animal experiment; animal tissue; apoptosis; article; bcl 2 gene; caspase 3 gene; caspase 7 gene; controlled study; gene; gene expression regulation; gene location; glucose blood level; glucose homeostasis; GPx gene; in vivo study; insulin blood level; insulin release; Mcl 1 gene; Mdm 2 gene; mouse; Nfr2 gene; nick end labeling; nonhuman; NOO1 gene; oxidative stress; pancreas injury; pancreas islet disease; toxicity testing; tumor suppressor gene; analysis; animal; apoptosis; blood; chemistry; cytology; drug effects; genetics; Institute for Cancer Research mouse; lipid peroxidation; male; metabolism; pancreas islet; Animals; Apoptosis; Blood Glucose; Caspase 3; Caspase 7; Glutathione Peroxidase; Insulin; Islets of Langerhans; Lipid Peroxidation; Male; Malondialdehyde; Mercuric Chloride; Methylmercury Compounds; Mice; Mice, Inbred ICR; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-mdm2; Reactive Oxygen Species; Tumor Suppressor Protein p53
Publisher
MDPI AG
Type
journal article