Chen L C, Tatum V, Glauert H P, Chow C K
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506-0054, USA.
J Biochem Mol Toxicol. 2001;15(2):107-13. doi: 10.1002/jbt.6.
Previously we have shown that treatment with the peroxisome proliferator perfluorodecanoic acid (PFDA) significantly increased hepatic reduced glutathione (GSH) content without altering the activity of selenium-glutathione peroxidase. In this study we examined some potential mechanisms by which PFDA treatment increases GSH levels. Male Sprague-Dawley rats were given a single injection of 0, 8.8, 17.5, and 35 mg PFDA in corn oil per kg body weight. Twelve days later the effects of PFDA on the activities of enzymes associated with GSH synthesis, utilization, and regeneration were assessed. The results showed that in a dose-dependent manner, PFDA treatment significantly decreased the activity of gamma-glutamylcysteine synthetase, while the activities of NADPH-generating enzymes, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase were increased. PFDA treatment also dose dependently decreased cytosolic, but not microsomal, glutathione S-transferase activity, and the activity of glutathione reductase was decreased by the highest dose of PFDA. The data obtained suggest that increased hepatic GSH levels following PFDA treatment may result from increased regeneration and/or decreased utilization.
此前我们已经表明，用过氧化物酶体增殖剂全氟癸酸（PFDA）处理可显著提高肝脏中还原型谷胱甘肽（GSH）的含量，而不会改变硒谷胱甘肽过氧化物酶的活性。在本研究中，我们研究了PFDA处理增加GSH水平的一些潜在机制。给雄性Sprague-Dawley大鼠每千克体重单次注射0、8.8、17.5和35毫克溶于玉米油的PFDA。十二天后，评估PFDA对与GSH合成、利用和再生相关的酶活性的影响。结果表明，PFDA处理以剂量依赖的方式显著降低了γ-谷氨酰半胱氨酸合成酶的活性，而产生NADPH的酶、苹果酸酶、葡萄糖-6-磷酸脱氢酶和6-磷酸葡萄糖酸脱氢酶的活性增加。PFDA处理还剂量依赖性地降低了胞质而非微粒体谷胱甘肽S-转移酶的活性，并且最高剂量的PFDA降低了谷胱甘肽还原酶的活性。所获得的数据表明，PFDA处理后肝脏GSH水平的增加可能是由于再生增加和/或利用减少所致。
