Depletion of circulating cyst(e)ine by oral and intravenous mesna

Abstract

The sulfhydryl status of normal and tumour cells is critically important in determining their susceptibility to various cytostatic agents. As a sulfhydryl compound, mesna (sodium 2-mercaptoethane-sulfonate) which is used in large doses to prevent haemorrhagic cystitis associated with certain chemotherapeutic regimens might derange cellular thiol homeostasis. In order to investigate the effects of mesna on the concentrations of thiols in plasma, cysteine, glutathione and their disulfides were measured by HPLC following the oral and intravenous administration of mesna to healthy volunteers. After 7.3 mmol mesna i.v. free cysteine rose from 8.2 (95% CI 7.0-9.4) nmol ml-1 to 53.6 (47.4-59.8) nmol ml-1 at 5 min, most likely due to reduction of circulating cystine by the sulfhydryl drug. This initial rise was followed by a marked decrease of total cyst(e)ine in plasma from 276 (215-337) nmol ml-1 to a nadir of 102 (89-115) nmol ml-1 between 30-120 min after infusion, most likely due to an increased uptake of cysteine into cells and an increased urinary excretion of cyst(e)ine. Qualitatively similar changes were seen after oral mesna. The present data indicate that mesna depletes circulating cyst(e)ine and may thereby markedly alter the sulfhydryl status of cells in vivo although the drug itself is not taken up by most cells.