Hexavalent chromium induces renal apoptosis and autophagy via disordering the balance of mitochondrial dynamics in rats

Ecotoxicol Environ Saf. 2020 Nov:204:111061. doi: 10.1016/j.ecoenv.2020.111061. Epub 2020 Aug 1.

Abstract

The use of hexavalent chromium (Cr(VI)) in many industrial processes has resulted in serious environmental pollution problems. Cr(VI) causes organ toxicity in animals after ingestion or inhalation. However, the exact mechanism by which Cr(VI) produces kidney damage remains elusive. Herein, we investigated whether Cr(VI)-induced kidney damage is related to the disorder of mitochondrial dynamics. In this study, 28 male rats were divided into four groups and intraperitoneally injected with 0, 2, 4, and 6 mg/kg body weight potassium dichromate for 5 weeks. Experiment included analysis of renal histopathology and ultrastructure, determination of biochemical indicators, and measurement of related protein content. The results showed that Cr(VI) induced kidney injury through promotion of oxidative stress, apoptosis, and disorder of mitochondrial dynamics in a dose-dependent manner. The protein levels of the silent information regulator two ortholog 1 (Sirt1), peroxisome proliferation-activated receptor-g coactivator-1a (PGC-1a), and autophagy-related proteins were significantly decreased after Cr(VI) exposure. These findings suggest that Cr(VI) leads to the disorder of mitochondrial dynamics by inhibiting the Sirt1/PGC-1a pathway, which leads to renal apoptosis and autophagy in rats.

Keywords: Apoptosis; Autophagy; Cr(VI); Mitochondrial dynamics; Renal injury.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Chromium / toxicity*
  • Dose-Response Relationship, Drug
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / ultrastructure
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Male
  • Mitochondrial Dynamics / drug effects*
  • Oxidative Stress / drug effects*
  • Potassium Dichromate / toxicity
  • Rats
  • Rats, Wistar

Substances

  • Chromium
  • chromium hexavalent ion
  • Potassium Dichromate