降血脂药物吉非贝齐、环丙贝特和氯贝酸对虹鳟肝细胞原代培养物中过氧化物酶体β氧化的影响。

Effect of hypolipidemic drugs gemfibrozil, ciprofibrate, and clofibric acid on peroxisomal beta-oxidation in primary cultures of rainbow trout hepatocytes.

作者信息

Donohue M, Baldwin L A, Leonard D A, Kostecki P T, Calabrese E J

机构信息

Environmental Health Sciences Program, School of Public Health, University of Massachusetts, Amherst 01003.

出版信息

Ecotoxicol Environ Saf. 1993 Oct;26(2):127-32. doi: 10.1006/eesa.1993.1044.

DOI:10.1006/eesa.1993.1044

PMID:7504609

Abstract

Primary cultures of hepatocytes were established from sexually mature male rainbow trout (Oncorhyncus mykiss) and treated with the hypolipidemic drugs gemfibrozil (0.25-1.25 mM), clofibric acid (2.25-3.00 mM), or ciprofibrate (0.25-1.00 mM). Significant dose-related increases in peroxisomal fatty acyl-CoA oxidase (FACO) were seen after exposure for 48 hr to clofibric acid (P < 0.01) and ciprofibrate (P < 0.05) but not gemfibrozil (P = 0.08). Strong correlation was obtained between increased acyl-CoA oxidase activity and the relative amount of peroxisomal bifunctional enzyme (PBE), further supporting evidence of a proliferative effect. These preliminary studies demonstrate that peroxisomal beta-oxidation can be induced in vitro in a primary rainbow trout hepatocyte system.

摘要

从性成熟的雄性虹鳟鱼（Oncorhyncus mykiss）中建立肝细胞原代培养物，并用降血脂药物吉非贝齐（0.25 - 1.25 mM）、氯贝酸（2.25 - 3.00 mM）或环丙贝特（0.25 - 1.00 mM）进行处理。暴露48小时后，氯贝酸（P < 0.01）和环丙贝特（P < 0.05）处理组的过氧化物酶体脂肪酰辅酶A氧化酶（FACO）出现显著的剂量相关增加，但吉非贝齐处理组未出现（P = 0.08）。酰基辅酶A氧化酶活性增加与过氧化物酶体双功能酶（PBE）的相对量之间存在强相关性，进一步支持了增殖效应的证据。这些初步研究表明，在原代虹鳟鱼肝细胞系统中可在体外诱导过氧化物酶体β-氧化。