Effects of selenium, zinc, insulin and metallothionein on cadmium-induced oxidative stress and metallothionein gene expression levels in diabetic rats

J Basic Clin Physiol Pharmacol. 2020 Mar 2;31(2):/j/jbcpp.2020.31.issue-2/jbcpp-2019-0198/jbcpp-2019-0198.xml. doi: 10.1515/jbcpp-2019-0198.

Abstract

Background The aim of this study was to investigate the effects of selenium, zinc, insulin, and metallothionein on oxidative damage and metallothionein (MT) gene expression levels in streptozotocin (STZ)-induced type 1 diabetic rats exposed to Cd. Methods Rats were categorized under eight groups (control, STZ, Cd, STZ + Cd, Group 5, Group 6, Group 7, and STZ + Cd + MT [n:8/group]) were used. After diabetes was induced by STZ (55 mg/kg, i.p.), Cd was administered (1 mg/kg CdCl, orally) for 4 weeks. In cadmium-treated groups selenium (Na2SeO3 1.5 mg/kg, i.p.), zinc (ZnSO4 10 mg/kg via oral gavage), insulin (insulin glargine, 2U/day, s.c.), and MT (1mg/kg, every other 10 days, s.c.) were administered. MT gene expression levels, MDA levels, GPx, SOD, and CAT activity levels were determined in liver and kidney tissues. Results MT gene expression and MDA levels increased (p < 0.05) while GPx and SOD activity levels decreased (p < 0.05) in STZ, Cd, and STZ + Cd groups. In Group 5, Group 6, Group 7, and Group 8 groups MT gene expression and MDA levels were decreased while GPx and SOD activity levels were increased (p < 0.05). CAT activity significantly increased (p < 0.05) in STZ + Cd group while there were no significance in other groups (p > 0.05). Compared to the control, Group 5, Group 6, Group 7, and Group 8 groups provided no difference for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine levels (p > 0.05). Conclusions Our results suggest that Se, insulin, Zn and MT may have protective effects against hepatotoxicity and nephrotoxicity caused by Cd exposure in diabetic rats by reducing oxidative stress and MT gene expression levels.

Keywords: cadmium; diabetes; gene expression; metallothionein; oxidative stress.

MeSH terms

  • Animals
  • Cadmium / toxicity
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Gene Expression Regulation / drug effects
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Kidney Diseases / prevention & control
  • Liver Diseases / prevention & control
  • Male
  • Metallothionein / administration & dosage
  • Metallothionein / genetics*
  • Metallothionein / pharmacology
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Selenium / administration & dosage
  • Selenium / pharmacology
  • Streptozocin
  • Zinc / administration & dosage
  • Zinc / pharmacology

Substances

  • Insulin
  • Cadmium
  • Streptozocin
  • Metallothionein
  • Selenium
  • Zinc