Glauert H P, Srinivasan S, Tatum V L, Chen L C, Saxon D M, Lay L T, Borges T, Baker M, Chen L H, Robertson L W
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506.
Biochem Pharmacol. 1992 Mar 17;43(6):1353-9. doi: 10.1016/0006-2952(92)90513-i.
The purpose of this study was to determine if hepatic cellular antioxidants and indices of oxidative damage are altered by administration of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid (PFDA). Rats were fed 0.01% ciprofibrate in the diet or were injected with PFDA (0.5 or 5.0 mg/kg, i.p.) every 4 weeks for 6, 14, 30, 54, and 78 weeks. Peroxisomal fatty acyl-CoA oxidase and catalase activities were increased by both ciprofibrate and PFDA throughout the study. Neither ciprofibrate nor PFDA increased the levels of malonaldehyde or conjugated dienes, but ciprofibrate decreased these indices at early time points. Ciprofibrate decreased the following cellular antioxidants or antioxidant enzymes: vitamin C, vitamin D, DT-diaphorase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase; superoxide dismutase and glutathione were not affected. PFDA decreased DT-diaphorase and increased superoxide dismutase, but did not affect other cellular antioxidants. This study shows that administration of the peroxisome proliferators ciprofibrate and PFDA did not increase indices of lipid peroxidation, but that cellular antioxidant defenses were inhibited for a prolonged period of time by the peroxisome proliferator ciprofibrate.
本研究的目的是确定给予过氧化物酶体增殖剂环丙贝特和全氟癸酸（PFDA）是否会改变肝细胞抗氧化剂及氧化损伤指标。给大鼠喂食含0.01%环丙贝特的饲料，或每4周腹腔注射PFDA（0.5或5.0 mg/kg），持续6、14、30、54和78周。在整个研究过程中，环丙贝特和PFDA均使过氧化物酶体脂肪酰辅酶A氧化酶和过氧化氢酶活性增加。环丙贝特和PFDA均未增加丙二醛或共轭二烯的水平，但环丙贝特在早期时间点使这些指标降低。环丙贝特降低了以下细胞抗氧化剂或抗氧化酶：维生素C、维生素D、DT-黄递酶、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶和谷胱甘肽还原酶；超氧化物歧化酶和谷胱甘肽未受影响。PFDA降低了DT-黄递酶并增加了超氧化物歧化酶，但未影响其他细胞抗氧化剂。本研究表明，给予过氧化物酶体增殖剂环丙贝特和PFDA不会增加脂质过氧化指标，但过氧化物酶体增殖剂环丙贝特会长期抑制细胞抗氧化防御。
