Metal-induced nephrotoxicity to diabetic and non-diabetic Wistar rats

Environ Sci Pollut Res Int. 2019 Oct;26(30):31111-31118. doi: 10.1007/s11356-019-06022-z. Epub 2019 Aug 27.


The present study was conducted to examine the nephrotoxic effects of heavy metals including lead (Pb), manganese (Mn), arsenic (As), and cadmium (Cd) in diabetic and non-diabetic Wistar rats. Animals were exposed to heavy metals for 30 days, Pb was injected as lead acetate (C4H6O4Pb), Mn was injected as manganese chloride (MnCl2), Cd was injected as cadmium chloride (CdCl2), and As was administered orally to rats in the form of sodium arsenite (AsO2Na). Results showed that metal deposition trends in tissues were Pb > As > Cd > Mn and the urinary metal levels were Pb > Cd > As > Mn. Diabetic metal alone, as well as metal mixture-treated groups, showed decreased urinary metal levels as compared with non-diabetic metal alone and metal mixture-treated groups. Both diabetic- and non-diabetic metal mixture-treated groups revealed an increasing trend of blood urea nitrogen (BUN) and serum creatinine. In addition, heavy metal treatments resulted in elevated malondialdehyde (MDA) levels in the kidney tissue while decreased levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GHS) were observed in the kidney tissue in comparison with the control group. The histological analysis of the kidney tissues showed tubular degeneration, fibrosis, and vacuolation as a result of heavy metal exposure. The present study revealed that co-exposure of heavy metals (Pb, Cd, Mn, As) induced more nephrotoxicity as compared with the metal alone treatment. Moreover, diabetic Wistar rats are more prone to kidney damage as a result of heavy metal exposure.

Keywords: Diabetes; Metal mixtures; Nephrotoxicity; Oxidative stress; Wistar rat.

MeSH terms

  • Animals
  • Catalase / metabolism
  • Creatinine / metabolism
  • Diabetes Mellitus / pathology*
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Male
  • Malondialdehyde / metabolism
  • Metals, Heavy / pharmacokinetics
  • Metals, Heavy / toxicity*
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Tissue Distribution


  • Metals, Heavy
  • Malondialdehyde
  • Creatinine
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione