Acute renal toxicity of sodium chlorate: Redox imbalance, enhanced DNA damage, metabolic alterations and inhibition of brush border membrane enzymes in rats

Environ Toxicol. 2018 Nov;33(11):1182-1194. doi: 10.1002/tox.22624. Epub 2018 Aug 24.

Abstract

Sodium chlorate (NaClO3 ) is widely used in paper and pulp industries and as a non-selective herbicide. Humans can be exposed to NaClO3 through contaminated drinking water due to its improper and unchecked usage in industries and as herbicide. NaClO3 is also present as a major stable by-product in drinking water that has been disinfected with chlorine dioxide. In this study, we have investigated the effect of a single acute oral dose of NaClO3 on rat kidney. Adult male Wistar rats were divided into one control and four NaClO3 treated groups that were orally given different doses of NaClO3 and euthanized 24 hr after the treatment. Oral administration of NaClO3 resulted in increased hydrogen peroxide levels, lipid, and protein oxidation while thiol and glutathione content and activities of brush border membrane enzymes were decreased in kidney in a NaClO3 dose-dependent manner. Significant alterations in the activities of enzymes involved in carbohydrate metabolism and antioxidant defense were also observed. Administration of NaClO3 induced DNA fragmentation and increased DNA-protein cross-linking. Histological studies showed marked damage in kidney from NaClO3 treated animals. These results strongly suggest that NaClO3 induces nephrotoxicity via redox imbalance that results in DNA and membrane damage, metabolic alterations and brush border membrane enzyme dysfunction.

Keywords: BBM; DNA damage; NaClO3; nephrotoxicity; oxidative stress.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Animals
  • Antioxidants / metabolism
  • Carbohydrate Metabolism / drug effects
  • Chlorates / toxicity*
  • DNA Damage
  • Glutathione / metabolism
  • Herbicides / toxicity*
  • Kidney / drug effects*
  • Kidney / enzymology
  • Kidney / pathology
  • Kidney / ultrastructure
  • Male
  • Microvilli / drug effects*
  • Microvilli / enzymology
  • Microvilli / pathology
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Toxicity Tests, Acute

Substances

  • Antioxidants
  • Chlorates
  • Herbicides
  • Glutathione
  • sodium chlorate