Alteration in plasma levels of nonprotein sulfhydryl compounds and S-nitrosothiols in chronic renal failure patients.

BACKGROUND: Uremia is accompanied by the elevated nitric oxide (NO) synthesis, and it has not yet been established how this influences the levels of nonprotein sulfhydryl compounds (NPSH) and formation of S-nitrosothiols (SNT). METHODS: Our study was designed to determine plasma levels of SNT and NPSH in chronic renal failure (CRF) patients, who were hemodialysed (HD) or were not on hemodialysis treatment (ND), and in the control group. RESULTS: In ND patients, the plasma levels of SNT were significantly increased (11.25+/-2.08 nmol/ml, p<0.01), while NPSH levels were simultaneously decreased (66.67+/-15.0 nmol/ml, p<0.05) in comparison with the control subjects (SNT: 8.75+/-2.08 nmol/ml, NPSH: 86.66 nmol/ml). In HD patients, plasma concentration of SNT before hemodialysis was significantly lower than in the control group (0.150+/-0.042 nmol/mg protein vs. control: 0.175+/-0.075 nmol/mg protein), and no significant change was observed after dialysis (0.142+/-0.058 nmol/mg protein, p<0.05). The level of NPSH in HD patients before dialysis was significantly decreased in comparison with the control subjects, both, when the results were calculated per 1 ml of plasma (45.96+/-17.87 nmol/ml) and per 1 mg of protein (0.70+/-0.25 nmol/mg protein). In the postdialysis samples, NPSH rose (79.15+/-22.9 nmol/ml, p<0.001 which corresponds to 1.30+/-0.55 nmol/mg protein, p<0.001) as compared to the level before dialysis. CONCLUSIONS: Firstly, plasma SNT level was found to be increased in CRF patients who were not treated with hemodialysis, while in HD patients, it dropped below the control values. It indicates that hemodialysis disturbs an equilibrium of reactions involved in S-nitrosothiols formation most probably by removing low molecular weight S-nitrosylating compounds. Secondly, the increased level of NPSH after each hemodialysis session indicates reestablished antioxidant capacity of plasma and suggests the existence of dialysable compounds, which via unknown mechanism become responsible for the decreased level of thiols.

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

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.