Oesch F, Hartmann R, Timms C, Strolin-Benedetti M, Dostert P, Wörner W, Schladt L
Institut für Toxikologie, Universität Mainz, Federal Republic of Germany.
J Cancer Res Clin Oncol. 1988;114(4):341-6. doi: 10.1007/BF02128176.
Fischer-344 rats and Hartley guinea pigs received a diet containing 0.01% (w/w), 0.05% (w/w), or 0.25% (w/w) of the hypolipidemic drug fenofibrate. Rats were treated for 4, 7, 14, or 21 days, and a clear dose-dependent and weak time-dependent increase in liver/body weight ratio was observed. The specific activity of peroxisomal beta-oxidation increased linearly with time at all concentrations used. A dose-dependent increase in cEH was observed, but the activity remained constant after treatment for 7 days. Enhancement of palmitoyl-CoA hydrolase was dose-dependent, but was similar at all 4 time points investigated. In contrast to the other enzyme activities, mEH was not or only minimally (less than 1.5-fold) induced. In contrast to the rat, treatment of guinea pigs with fenofibrate for 1 week did not change liver weight or enzyme activities. Prolonged treatment of guinea pigs (4 weeks) with fenofibrate did not result in an increase in enzyme activities. This was also observed with clofibrate whereas tiadenol caused a slight increase in enzyme activities (1.5- to 2.6-fold). In contrast to the guinea pig each of the three hypolipidemic drugs led to an increase in enzyme activities in the rat liver after treatment for 1 week.
将高脂血症药物非诺贝特按0.01%（重量/重量）、0.05%（重量/重量）或0.25%（重量/重量）添加到饲料中，分别喂饲费希尔344大鼠和哈特利豚鼠。大鼠接受4天、7天、14天或21天的处理，结果观察到肝/体重比呈明显的剂量依赖性增加，且时间依赖性较弱。在所使用的所有浓度下，过氧化物酶体β氧化的比活性均随时间呈线性增加。观察到羧酸酯酶（cEH）呈剂量依赖性增加，但在处理7天后其活性保持恒定。棕榈酰辅酶A水解酶的增强呈剂量依赖性，但在所有4个研究时间点均相似。与其他酶活性不同，微粒体环氧水解酶（mEH）未被诱导或仅被轻微诱导（小于1.5倍）。与大鼠不同，用非诺贝特处理豚鼠1周未改变肝脏重量或酶活性。用非诺贝特对豚鼠进行长期处理（4周）未导致酶活性增加。氯贝丁酯也观察到了这种情况，而噻二诺则使酶活性略有增加（1.5至2.6倍）。与豚鼠不同，三种高脂血症药物中的每一种在处理大鼠1周后均导致大鼠肝脏酶活性增加。
