Kang Y J, Uthus E O
Department of Pharmacology and Toxicology, University of North Dakota School of Medicine, Grand Forks 58202, USA.
Biochem Pharmacol. 1996 Feb 23;51(4):567-70. doi: 10.1016/0006-2952(95)02221-x.
Glutathione (GSH) is an important factor involved in the resistance of tumor cells to anticancer agents. Buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, effectively decreases cellular GSH concentrations both in vitro and in vivo. Depletion of GSH by BSO sensitizes a variety of cancer cells to chemotherapeutic agents. Therefore, BSO has been on clinical trial as an anticancer adjuvant. For this purpose, it is important to understand the effect of BSO treatment not only on the sensitivity of tumor cells to anticancer agents, but also on the metabolism and function of normal tissues. The present study was undertaken to determine the effect of BSO treatment on GSH concentrations in the blood, liver, and ovary, and changes in concentrations of ovarian hormones and other important components in plasma. Female Sprague-Dawley rats, 90 days of age, were treated with 2.0 mmol/kg BSO in saline by intraperitoneal injection, twice daily for 7 days. This treatment depressed GSH concentrations in the blood, liver and ovary by 95, 75, and 85%, respectively. Several blood components were measured. These included red blood cells, hemoglobin, ceruloplasmin, hematocrit, mean corpuscular volume and hemoglobin concentration, alkaline phosphatase, urea nitrogen, creatine and creatinine, glucose, cholesterol, triglycerides, triiodothyronine (T3), thyroxine (T4), and hormones including estradiol, progesterone, and prolactin. BSO treatment significantly (P < 0.05) elevated and lowered plasma concentrations of ceruloplasmin and urea nitrogen, respectively, More importantly, plasma concentrations of estradiol and progesterone were decreased markedly (P < 0.05) in the BSO-treated animals. The hormonal results suggest that investigations on the role of BSO-induced GSH depletion in the treatment of malignancies both with and without hormone dependence in women should be undertaken.
谷胱甘肽（GSH）是肿瘤细胞对抗癌药物产生抗性的一个重要因素。丁硫氨酸亚砜胺（BSO）是GSH合成的特异性抑制剂，在体外和体内均能有效降低细胞内GSH浓度。BSO导致的GSH耗竭可使多种癌细胞对化疗药物敏感。因此，BSO已作为抗癌佐剂进入临床试验阶段。出于这个目的，了解BSO治疗不仅对肿瘤细胞对抗癌药物敏感性的影响，还对正常组织的代谢和功能的影响非常重要。本研究旨在确定BSO治疗对血液、肝脏和卵巢中GSH浓度的影响，以及血浆中卵巢激素和其他重要成分浓度的变化。90日龄的雌性斯普拉格-道利大鼠，通过腹腔注射给予2.0 mmol/kg BSO的生理盐水溶液，每日两次，共7天。该处理分别使血液、肝脏和卵巢中的GSH浓度降低了95%、75%和85%。检测了几种血液成分，包括红细胞、血红蛋白、铜蓝蛋白、血细胞比容、平均红细胞体积和血红蛋白浓度、碱性磷酸酶、尿素氮、肌酸和肌酐、葡萄糖、胆固醇、甘油三酯、三碘甲状腺原氨酸（T3）、甲状腺素（T4）以及包括雌二醇、孕酮和催乳素在内的激素。BSO处理分别显著（P < 0.05）升高和降低了血浆中铜蓝蛋白和尿素氮的浓度，更重要的是，在接受BSO处理的动物中，血浆中雌二醇和孕酮的浓度显著降低（P < 0.05）。这些激素结果表明，应该对BSO诱导的GSH耗竭在治疗女性激素依赖性和非激素依赖性恶性肿瘤中的作用进行研究。
