title: Oral exposure of mice to cadmium (II), chromium (VI) and their mixture induce oxidative- and endoplasmic reticulum-stress mediated apoptosis in the livers.
abstract: Health concerns regarding the environmental heavy metals in wildlife and humans have increased in recent years. We evaluated the effects of exposure of mice to low doses of cadmium (Cd), chromium (Cr) and their mixtures on oxidative- and ER-stress. Male adult mice were orally exposed to Cd (0.5 and 2 mg kg(-1) ), Cr (1 and 4 mg kg(-1) ) and binary Cd+Cr mixtures (0.25 + 05 and 1 + 2 mg kg(-1) ) daily for 36 days. We observed that the bioaccumulation of Cd and Cr in the liver in a dose-dependent manner, and the Cd and Cr contents in the 2 mg kg(-1) Cd and 4 mg kg(-1) Cr treated groups reached 2.43 and 3.46 µg g(-1) liver weight. In addition, treatments with 2 mg kg(-1) Cd, 4 mg kg(-1) Cr or their mixture (1 + 2 mg kg(-1) ) significantly decreased body and liver weights, increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and activities of catalase (CAT) and glutathione peroxidase (GPX) in the liver. Moreover, Cd and Cr exposures also elevated the transcription of the oxidative- and endoplasmic reticulum (ER)-stress related genes including Cat, Gpx, heme oxygenase 1 (Ho-1), regulated protein 78 (Grp78), activating transcription factor 6 (Atf6) and proaoptotic CCAAT/-enhancer-binding protein homologous protein (Chop) in a dose dependent manner in the liver. And hepatic cytochrome c levels increased in all Cd, Cr or their mixture treated groups. Furthermore, the transcriptional status and the activities of Caspase 9 and Caspase 3 were increased significantly in the liver when exposed to high doses of Cd, Cr or their mixture. These results suggested that a long period exposure of mice to Cd or Cr has the potential to elicit oxidative- and ER-stress mediated apoptosis in their livers. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 693-705, 2016.
authors.affiliation: Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Songbin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Runhua
authors.initials: R
authors.lastname: Tao
authors.affiliation: Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Lanya
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Biotechnology, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, 310032, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002857:Chromium / Q000633:toxicity*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D004785:Environmental Pollutants; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; D017382:Reactive Oxygen Species; D002104:Cadmium; D002857:Chromium
keywords: apoptosis; cadmium; chromium; endoplasmic reticulum stress; mice; oxidative stress