title: Zinc treatment prevents type 1 diabetes-induced hepatic oxidative damage, endoplasmic reticulum stress, and cell death, and even prevents possible steatohepatitis in the OVE26 mouse model: Important role of metallothionein.
abstract: Whether zinc is able to improve diabetes-induced liver injury remains unknown. Transgenic type 1 diabetic (OVE26) mice develop hyperglycemia at 3 weeks old; therefore therapeutic effect of zinc on diabetes-induced liver injury was investigated in OVE26 mice. Three-month old OVE26 and age-matched wild-type mice were treated by gavage with saline or zinc at 5mg/kg body-weight every other day for 3 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level with liver histopathological and biochemical changes. OVE26 mice at 6 months old showed significant increases in serum ALT level and hepatic oxidative damage, endoplasmic reticulum stress and associated cell death, mild inflammation, and fibrosis. However, all these hepatic morphological and functional changes were significantly prevented in 3-month zinc-treated OVE26 mice. Mechanistically, zinc treatment significantly increased hepatic metallothionein, a protein with known antioxidant activity, in both wild-type and OVE26 mice. These results suggest that there were significantly functional, structural and biochemical abnormalities in the liver of OVE26 diabetic mice at 6 months old; however, all these changes could be prevented with zinc treatment, which was associated with the upregulation of hepatic metallothionein expression.
authors.affiliation: Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China; The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China; Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liang
authors.affiliation: Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China; Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China; The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Weixia
authors.initials: W
authors.lastname: Sun
authors.affiliation: The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China; The Key Laboratory of Pathobiology of Ministry of Education at The Norman Bethune Medical College of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA; The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China; Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA; The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China; Kosair Children's Hospital Research Institute, The Department of Pediatrics of the University of Louisville, Louisville, KY 40202, USA. Electronic address: l0cai001@louisville.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: The RuiAn Center of Chinese-American Research Institute for Diabetic Complications, The Department of Endocrinology of The Third Affiliated Hospital of Wenzhou Medical University, RuiAn, Zhejiang 325200, China.
authors.forename: Xuemian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Infectious Diseases, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, China. Electronic address: chengml@21cn.com.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D002645:Chickens; D003094:Collagen / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005234:Fatty Liver / Q000517:prevention & control*; D008111:Liver Function Tests; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D015032:Zinc / Q000627:therapeutic use*
chemical_list: D003094:Collagen; D008668:Metallothionein; D015032:Zinc
keywords: Diabetic complications; ER stress; Hepatic dysfunction; Liver injury; Metallothionein; Zinc