Charmoillaux M, Goudonnet H, Mounié J, Magdalou J, Escousse A, Truchot R C
Formation de Biochimie pharmacologique, UFR Pharmacie, Dijon.
C R Seances Soc Biol Fil. 1990;184(5-6):370-9.
The influence of thyroid hormones upon the inductive effects on microsomal enzymes and the hepatic proliferation produced by different fibrates was studied in the male rat. A pharmacological dose of triiodo-L-thyronine significantly lowers the total cytochrome P450 content induced by some equi-effective doses of clofibrate, ciprofibrate, bezafibrate and fenofibrate. The ethoxycoumarin O-deethylase activity (ECOD) is concomitantly decreased. On the contrary, L-T3 accentuates the specific inductive effect of fibrates on bilirubin-UDPGT activity. Hypothyroid has little or no influence upon the effect of fibrates towards cytochrome P450 content and ECOD activity. On the other hand, this thyroid status significantly lowers the CN- palmitoyl coenzyme A dehydrogenase, which is a marker enzyme of the peroxisome proliferation caused by the different fibrates. These results indicate a possible modulation of thyroid hormones within the fibrates induction mechanism in the rat.
在雄性大鼠中研究了甲状腺激素对不同贝特类药物诱导微粒体酶及肝脏增殖的影响。药理学剂量的三碘 - L - 甲状腺原氨酸显著降低了某些等效剂量的氯贝丁酯、环丙贝特、苯扎贝特和非诺贝特诱导的总细胞色素P450含量。乙氧香豆素O - 脱乙基酶活性(ECOD)也随之降低。相反,L - T3增强了贝特类药物对胆红素 - UDPGT活性的特异性诱导作用。甲状腺功能减退对贝特类药物对细胞色素P450含量和ECOD活性的影响几乎没有影响。另一方面,这种甲状腺状态显著降低了CN - 棕榈酰辅酶A脱氢酶,该酶是不同贝特类药物引起的过氧化物酶体增殖的标记酶。这些结果表明甲状腺激素在大鼠贝特类药物诱导机制中可能具有调节作用。