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Mercuric Compounds Induce Pancreatic Islets Dysfunction and Apoptosis in Vivo
Department of Urology, China Medical University Hospital, and School of Medicine, China Medical University, No.2 Yuh-Der Rd., Taichung 404, Taiwan
Institute of Toxicology, College of Medicine, National Taiwan University, No.1 Jen-Ai Rd., Section 1, Taipei 100, Taiwan
Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, No.135 Nanxiao St. Changhua City, Changhua County 500, Taiwan
Department of Occupational Safety and Health, College of Health Care and Management, Chung Shan Medical University, Taiwan
Department of Surgery, National Taiwan University Hospital, and Department of Surgery, College of Medicine, National Taiwan University, Taipei 10043, Taiwan
Department of Emergency, Buddhist Tzu Chi General Hospital, Taichung Branch, No. 66 Section 1, Fongsing Rd., Tanzih Township, Taichung 427, Taiwan
Department of Occupational Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
Department of Physiology and Graduate Institute of Basic Medical Science, School of Medicine, College of Medicine, China Medical University, No.91 Hsueh-Shih Rd., Taichung 404, Taiwan
School of Chinese Medicine, College of Chinese Medicine, China Medical University, No.91 Hsueh-Shih Rd., Taichung 404, Taiwan
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 2 July 2012; in revised form: 2 September 2012 / Accepted: 17 September 2012 / Published: 26 September 2012
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.
Keywords: mercuric compounds; pancreatic islets; oxidative stress; apoptosis
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Chen, K.-L.; Liu, S.-H.; Su, C.-C.; Yen, C.-C.; Yang, C.-Y.; Lee, K.-I.; Tang, F.-C.; Chen, Y.-W.; Lu, T.-H.; Su, Y.-C.; Huang, C.-F. Mercuric Compounds Induce Pancreatic Islets Dysfunction and Apoptosis in Vivo. Int. J. Mol. Sci. 2012, 13, 12349-12366.
Chen K-L, Liu S-H, Su C-C, Yen C-C, Yang C-Y, Lee K-I, Tang F-C, Chen Y-W, Lu T-H, Su Y-C, Huang C-F. Mercuric Compounds Induce Pancreatic Islets Dysfunction and Apoptosis in Vivo. International Journal of Molecular Sciences. 2012; 13(10):12349-12366.
Chen, Kuo-Liang; Liu, Shing-Hwa; Su, Chin-Chuan; Yen, Cheng-Chieh; Yang, Ching-Yao; Lee, Kuan-I; Tang, Feng-Cheng; Chen, Ya-Wen; Lu, Tien-Hui; Su, Yi-Chang; Huang, Chun-Fa. 2012. "Mercuric Compounds Induce Pancreatic Islets Dysfunction and Apoptosis in Vivo." Int. J. Mol. Sci. 13, no. 10: 12349-12366.