The effect of the uremic toxin cyanate (CNO⁻) on anaerobic cysteine metabolism and oxidative processes in the rat liver: a protective effect of lipoate.

Abstract

Chronic renal failure (CRF) patients have an increased plasma level of urea, which can be a source of cyanate. This compound can cause protein carbamoylation thereby changing biological activity of proteins. Therefore, in renal failure patients, cyanate can disturb metabolism and functioning of the liver. This work presents studies demonstrating that the treatment of rats with cyanate alone causes the following changes in the liver: (1) inhibition of rhodanese (TST), cystathionase (CST) and 3-mercaptopyruvate sulfotransferase (MPST) activities, (2) decrease in sulfane sulfur level (S*), (3) lowering of nonprotein sulfhydryl groups (NPSH) group level, and (4) enhancement of prooxidant processes (rise in reactive oxygen species (ROS) and malondialdehyde (MDA) level). This indicates that cyanate inhibits anaerobic cysteine metabolism and shows prooxidant action in the liver. Out of the above-mentioned changes, lipoate administered with cyanate jointly was able to correct MDA, ROS and NPSH levels, and TST activity. It had no significant effect on MPST and CST activities. It indicates that lipoate can prevent prooxidant cyanate action and cyanate-induced TST inhibition. These observations can be promising for CRF patients since lipoate can play a dual role in these patients as an efficient antioxidant defense and a protection against cyanate and cyanide toxicity.

• Authors: Maria Sokołowska, Ewa Niedzielska, Małgorzata Iciek, Anna Bilska, Elżbieta Lorenc-Koci, Lidia Włodek
• Journal: Toxicology mechanisms and methods (Toxicol Mech Methods) Vol. 21 Issue 6 Pg. 473-8 (Jul 2011) ISSN: 1537-6524 [Electronic] England
• PMID: 21417628 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Cyanates
• Oxidants
• Poisons
• Reactive Oxygen Species
• Sulfhydryl Compounds
• Thioctic Acid
• Thiosulfate Sulfurtransferase
• potassium cyanate
• Cysteine
• Hydrogen Sulfide

Topics

• Animals
• Antioxidants (therapeutic use)
• Cyanates (toxicity)
• Cysteine (metabolism)
• Hydrogen Sulfide (metabolism)
• Kidney Failure, Chronic (drug therapy)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, enzymology, metabolism)
• Male
• Molecular Targeted Therapy
• Oxidants (toxicity)
• Oxidative Stress (drug effects)
• Poisons (toxicity)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)
• Sulfhydryl Compounds (metabolism)
• Thioctic Acid (therapeutic use)
• Thiosulfate Sulfurtransferase (metabolism)
• Uremia (chemically induced, metabolism, prevention & control)