The effect of uremic toxin cyanate (OCN–) on anaerobic sulfur metabolism and prooxidative processes in the rat kidney: a protective role of lipoate

Hum Exp Toxicol. 2011 Oct;30(10):1601-8. doi: 10.1177/0960327110394225. Epub 2010 Dec 22.

Abstract

Cyanate and its active form isocyanate are formed mainly in the process of nonenzymatic urea biodegradation. Cyanate is capable of protein S- and N-carbamoylation, which can affect their activity. The present studies aimed to demonstrate the effect of cyanate on activity of the enzymes implicated in anaerobic cysteine metabolism and cyanide detoxification and on glutathione (GSH) level and peroxidative processes in the kidney. In addition, we examined whether a concomitant treatment with lipoate, a dithiol that may act as a target of S-carbamoylation, can prevent these changes. The studies were conducted in Wistar rats. The animals were assigned to four groups, which received injections of physiological saline, cyanate (200 mg/kg), cyanate (200 mg/kg) + lipoate (100 mg/kg) and lipoate alone (100 mg/kg). The animals were killed 2 h after the first injection, the kidneys were isolated and kept at -80°C until biochemical assays were performed. Cyanate inhibited rhodanese (TST) and mercaptopyruvate sulfotransferase (MPST) activity, decreased GSH level and enhanced peroxidative processes in the kidney. All these changes were abolished by cyanate treatment in combination with lipoate.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cyanates / toxicity*
  • Cysteine / metabolism
  • Glutathione / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sulfur / metabolism
  • Sulfurtransferases / metabolism
  • Thioctic Acid / pharmacology*
  • Thiosulfate Sulfurtransferase / metabolism

Substances

  • Antioxidants
  • Cyanates
  • Reactive Oxygen Species
  • Malondialdehyde
  • Sulfur
  • Thioctic Acid
  • Sulfurtransferases
  • Thiosulfate Sulfurtransferase
  • 3-mercaptopyruvate sulphurtransferase
  • potassium cyanate
  • Glutathione
  • Cysteine