Stofer-Vogel B, Cerny T, Küpfer A, Junker E, Lauterburg B H
Department of Clinical Pharmacology, University of Bern, Switzerland.
Br J Cancer. 1993 Sep;68(3):590-3. doi: 10.1038/bjc.1993.391.
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.
正常细胞和肿瘤细胞的巯基状态对于确定它们对各种细胞生长抑制剂的敏感性至关重要。作为一种巯基化合物，美司钠（2-巯基乙烷磺酸钠）大剂量使用以预防与某些化疗方案相关的出血性膀胱炎，可能会扰乱细胞内硫醇的稳态。为了研究美司钠对血浆中硫醇浓度的影响，在健康志愿者口服和静脉注射美司钠后，通过高效液相色谱法测定了半胱氨酸、谷胱甘肽及其二硫化物的含量。静脉注射7.3 mmol美司钠后，游离半胱氨酸在5分钟时从8.2（95%可信区间7.0 - 9.4）nmol/ml升至53.6（47.4 - 59.8）nmol/ml，最可能的原因是巯基药物使循环中的胱氨酸还原。这一初始升高之后，血浆中总胱氨酸在输注后30 - 120分钟之间从276（215 - 337）nmol/ml显著下降至最低点102（89 - 115）nmol/ml，最可能的原因是细胞对半胱氨酸的摄取增加以及胱氨酸的尿排泄增加。口服美司钠后观察到定性相似的变化。目前的数据表明，美司钠会消耗循环中的胱氨酸，从而可能在体内显著改变细胞的巯基状态，尽管该药物本身不会被大多数细胞摄取。
