potassium-cyanate and Uremia

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.

Topics: Animals; Antioxidants; Cyanates; Cysteine; Hydrogen Sulfide; Kidney Failure, Chronic; Lipid Peroxidation; Liver; Male; Molecular Targeted Therapy; Oxidants; Oxidative Stress; Poisons; Rats; Rats, Wistar; Reactive Oxygen Species; Sulfhydryl Compounds; Thioctic Acid; Thiosulfate Sulfurtransferase; Uremia

Previous studies have shown that the increase of carbamylated LDL (cLDL), a product of nonenzymatic modification of LDL in human serum by urea-derived cyanate, may cause cardiovascular complications in patients with chronic renal insufficiency. This study examined the inhibitory effect of ascorbic acid, alpha-tocopherol and lycopene on LDL carbamylation in an in vitro model system.. After isolation of LDL from plasma using an ultracentrifuge technique, cyanate was added to it and then LDL carbamylation was measured in both the absence and presence of ascorbic acid, alpha-tocopherol and/or lycopene by the colorimetric method at 530 nm.. The findings indicated that these vitamins inhibit LDL carbamylation and the most effective vitamin of the three is lycopene. Moreover, the effect of lycopene on this process increased in the presence of ascorbic acid and alpha-tocopherol.. This study indicated that ascorbic acid, alpha-tocopherol and lycopene with antioxidant activity can probably inhibit LDL carbamylation and therefore may have a role in ameliorating atherosclerotic risk of patients with kidney failure. However in vitro and in vivo investigations are required to confirm the exact effects of these vitamins on patients suffering from uremic disorders.

Topics: Adult; alpha-Tocopherol; Ascorbic Acid; Atherosclerosis; Carotenoids; Citrulline; Cyanates; Electrophoresis, Agar Gel; Humans; Lipoproteins, LDL; Lycopene; Male; Protein Processing, Post-Translational; Uremia; Vitamins; Young Adult

Procaine esterase activity in plasma from patients with renal failure is decreased by 40%. Since cyanate is formed from urea and readily carbamylates certain blood proteins, a possible role for cyanate in the depression of plasma esterase activity in uraemic patients was considered. However, in vitro carbamylation of normal plasma in a range similar to that detected in uraemic patients did not influence procaine esterase activity. Kinetic analysis of the reaction showed that the maximal hydrolyzing capacity but not the Km in uraemic plasma was diminished (5.0 +/- 0.3 X 10(-5) moles hydrolyzed per litre of plasma per minute and a Km of 3.9 +/- 0.2 X 10(-5) mol/l in plasma from normal volunteers as compared to 3.1 +/- 0.1 X 10(-5) mol/l/min and 3.5 +/- 0.2 X 10(-5) ml/l in plasma from patients with renal failure). Therefore, not carbamylation but rather a decrease in enzyme synthesis is the likely explanation for the lower rate of procaine hydrolysis in uraemic plasma.

Topics: Adult; Cyanates; Esterases; Female; Half-Life; Humans; Hydrolysis; Kinetics; Male; Procaine; Uremia

The effects of in vitro carbamylation of plasma with potassium cyanate on drug-protein binding have been investigated. Potassium cyanate added to samples of normal plasma and incubated for 30 to 150 min induced time-related plasma protein carbamylation. Carbamylation of plasma did not influence quinidine protein binding, but resulted in decreased salicylate binding. The increased free fraction of salicylate in plasma correlated with the degree of carbamylation of plasma proteins (r = 0.99; p less than 0.001). Plasma from patients with chronic renal disease showed varying degrees of plasma protein carbamylation, correlating with the values of free plasma salicylate (r = 0.80; p less than 0.05). Scatchard plots for sulfadiazine binding in plasma from patients with uremia and in normal plasma carbamylated in vitro with potassium cyanate showed changes in the 2 groups when compared with those in normal individuals. If cyanate is produced in vivo from urea in patients with uremia, plasma protein carbamylation may play a role in the decreased plasma protein binding of some acidic drugs.

Topics: Adult; Binding Sites; Binding, Competitive; Blood Proteins; Carbamates; Charcoal; Cyanates; Female; Humans; In Vitro Techniques; Kinetics; Male; Protein Binding; Salicylates; Serum Albumin; Sulfadiazine; Time Factors; Urea; Uremia