给大鼠服用氯贝丁酯和氯苯那酯后肝脏过氧化氢酶和甘油磷酸脱氢酶活性增加。

Increase in hepatic catalase and glycerol phosphate dehydrogenase activities on administration of clofibrate and clofenapate to the rat.

Krishnakantha T P, Kurup C K

Biochem J. 1972 Nov;130(1):167-75. doi: 10.1042/bj1300167.

Abstract

Clofenapate (methyl 2-[4-(p-chlorophenyl)phenoxy]-2-methylpropionate) fed to the rat in the diet increased the content of mitochondrial protein in the liver by 50-60%. In this respect it resembled the related compound clofibrate (ethyl alpha-p-chlorophenoxyisobutyrate), which is widely used as an antihypercholesterolaemic drug. 2. Both compounds when fed to the rat enhanced the activity of alpha-glycerol phosphate dehydrogenase in the liver mitochondria manyfold, but were without effect on the enzyme in the soluble fraction. 3. On the other hand, the catalase activity in the supernatant fraction increased twofold after administration of the drugs. The mitochondrial catalase activity showed a consistent decrease. 4. It was unlikely that under the influence of the drug the increase in catalase activity took place in the mitochondrial particles and was leached into the cytosol during isolation. 5. The increase in catalase activity in the cytosol under the influence of the drug is best explained on the assumption that peroxisomes which contain this enzyme, and which are known to increase on administration of the drug, were broken during the process of cellular fractionation and released the enzyme into the cytosol. 6. All the above effects shown by both drugs were fully reversed when drugs were withdrawn from the diet. 7. Clofenapate was effective in bringing about the above changes when administered to the animal at one-hundredth the concentration of clofibrate.

摘要

氯苯那酯（2-[4-(对氯苯基)苯氧基]-2-甲基丙酸甲酯）添加到大鼠饮食中，可使肝脏线粒体蛋白含量增加50%至60%。在这方面，它类似于相关化合物氯贝丁酯（α-对氯苯氧基异丁酸乙酯），后者被广泛用作抗高胆固醇血症药物。2. 给大鼠喂食这两种化合物后，均可使肝脏线粒体中的α-甘油磷酸脱氢酶活性提高数倍，但对可溶性部分的该酶无影响。3. 另一方面，给药后上清液部分的过氧化氢酶活性增加了两倍。线粒体过氧化氢酶活性持续下降。4. 在药物影响下，过氧化氢酶活性的增加不太可能发生在线粒体颗粒中，并在分离过程中被浸出到胞质溶胶中。5. 药物影响下胞质溶胶中过氧化氢酶活性的增加，最好的解释是假设含有该酶的过氧化物酶体，已知在给药后会增加，在细胞分级分离过程中被破坏，并将酶释放到胞质溶胶中。6. 当从饮食中撤掉药物时，这两种药物所表现出的上述所有效应均可完全逆转。7. 当以氯贝丁酯浓度的百分之一给动物施用氯苯那酯时，它能有效地引起上述变化。