Disruption of thiol homeostasis in plasma of terminal renal failure patients

Abstract

Background The aim of the present studies was to investigate the changes in concentrations of different forms of thiols in plasma of terminal renal failure patients before and after hemodialysis. Methods Total concentrations of thiols, their free forms and the level of their mixed disulfides with proteins were determined with HPLC. Results In terminal renal failure patients before dialysis, total concentrations of cysteine, homocysteine and cysteinylglycine and their free and protein-bound fractions increased while level of all such forms of glutathione dropped. A single dialysis session caused short-lasting return of concentrations of all forms of thiols to the level equal or close to the control group. The changes observed in non-dialyzed patients were similar to those observed in dialyzed patients before single dialysis procedure. Conclusions The obtained results showed severe disturbance of thiol homeostasis in plasma of terminal renal failure patients. The following changes have to be emphasized: (1) high level of free cysteine (cystine) fraction, (2) strong tendency of homocysteine to form mixed disulfides with proteins, (3) drop of glutathione level. These observations confirm a suggestion that atherogenic action of homocysteine can be a result of S-homocysteinylation and N-homocysteinylation reactions, whereas toxic action of cysteine can result from auto-oxidation reaction.