DEPLETION OF CIRCULATING CYST(E)INE BY ORAL AND INTRAVENOUS MESNA

The sulfhydryl status of normal and tumour cells is critically importa nt in determining their susceptibility to various cytostatic agents. A s a sulfhydryl compound, mesna (sodium 2-mercaptoethane-sulfonate) whi ch is used in large doses to prevent haemorrhagic cystitis associated with certain chemotherapeutic regimens might derange cellular thiol ho meostasis. In order to investigate the effects of mesna on the concent rations of thiols in plasma, cysteine, glutathione and their disulfide s were measured by HPLC following the oral and intravenous administrat ion of mesna to healthy volunteers. After 7.3 mmol mesna i.v. free cys teine rose from 8.2 (95% CI 7.0-9.4) nmol ml-1 to 53.6 (47.4-59.8) nmo l ml-1 at 5 min, most likely due to reduction of circulating cystine b y the sulfhydryl drug. This initial rise was followed by a marked decr ease of total cyst(e)ine in plasma from 276 (215-337) nmol ml-1 to a n adir 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 incre ased urinary excretion of cyst(e)ine. Qualitatively similar changes we re seen after oral mesna. The present data indicate that mesna deplete s 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 m ost cells.