Lake B G, Gray T J, Pels Rijcken W R, Beamand J A, Gangolli S D
Xenobiotica. 1984 Mar;14(3):269-76. doi: 10.3109/00498258409151411.
A study was conducted of the effects of 10 hypolipidaemic agents on peroxisomal and microsomal enzyme activities in primary cultures of rat hepatocytes. Treatment with compounds such as Wy-14,643, tiadenol, nafenopin, BR-931, clofibrate and mono-(2-ethylhexyl)phthalate induced cyanide-insensitive palmitoyl-CoA oxidation (a specific peroxisomal marker enzyme), a polypeptide with a molecular weight of 80,000 associated with peroxisome proliferation, and carnitine acetyltransferase activity, after 70 h of culture. These compounds also maintained hepatocyte cytochrome P-450 levels and markedly induced lauric acid hydroxylation, whereas little effect was observed on 7-ethoxycoumarin O-deethylase. Studies with metyrapone, which also maintains cytochrome P-450, suggested that treatment with the hypolipidaemic agents resulted in the formation of different form(s) of cytochrome P-450 to those present in control cultures. Regression analysis demonstrated a high correlation between the induction of the peroxisomal parameters and lauric acid hydroxylation. The results indicate that hypolipidaemic agents which stimulate hepatic peroxisomal enzyme activities also induce novel form(s) of cytochrome P-450 with high specificity towards lauric acid hydroxylation. Both these processes may depend therefore on common receptor(s) which are retained in primary cultures of rat hepatocytes.
一项关于10种降血脂药物对大鼠肝细胞原代培养物中过氧化物酶体和微粒体酶活性影响的研究。用诸如Wy-14,643、替阿地诺、氯苯丁酯、BR-931、氯贝丁酯和邻苯二甲酸单（2-乙基己基）酯等化合物处理70小时后，诱导了对氰化物不敏感的棕榈酰辅酶A氧化（一种特定的过氧化物酶体标记酶）、一种与过氧化物酶体增殖相关的分子量为80,000的多肽以及肉碱乙酰转移酶活性。这些化合物还维持了肝细胞细胞色素P-450水平，并显著诱导了月桂酸羟化，而对7-乙氧基香豆素O-脱乙基酶的影响很小。用同样能维持细胞色素P-450的甲吡酮进行的研究表明，降血脂药物处理导致形成了与对照培养物中存在的细胞色素P-450不同形式的细胞色素P-450。回归分析表明，过氧化物酶体参数的诱导与月桂酸羟化之间存在高度相关性。结果表明，刺激肝脏过氧化物酶体酶活性的降血脂药物也诱导了对月桂酸羟化具有高特异性的新型细胞色素P-450形式。因此，这两个过程可能都依赖于大鼠肝细胞原代培养物中保留的共同受体。
