Iwasaki M, Kato H, Ariyoshi N, Oguri K
Department of Hygienic and Forensic Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka.
Fukuoka Igaku Zasshi. 1995 May;86(5):144-52.
The hyperlipidemia is a well-known typical symptom in Yusho patients and experimental animals treated with PCBs. We have found a significant induction of CYP4A1, which catalyzes omega-hydroxylation of fatty acids, in guinea pigs by the treatment with a coplanar PCB, 3, 4, 5, 3',4-pentachlorobiphenyl (PenCB), though the P450 is reduced in the treated rats. Peroxisome has beta-oxidation enzymes distinct from mitochondrial enzymes, and also play an important role in lipid metabolism. Peroxisome proliferators have been shown to regulate the expression of CYP4A1 and peroxisomal enzymes by the same mechanism in the rat. In the present study, we examine the effect of PenCB treatment on peroxisomal enzymes in the liver of guinea pigs. As a result, the enzyme activities of hepatic peroxisome, e.g. fatty acid oxidizing system, catalase and urate oxidase, had a rising tendency by the treatment with PenCB in the animal. The results suggest that the regulation of peroxisomal enzymes and CYP4A1 is also associated in guinea pigs, and PenCB provides a similar effect of peroxisomal proliferators to the animal. The possible toxicity through the peroxisomal alteration was discussed.
高脂血症是米糠油事件患者和用多氯联苯处理的实验动物中一种众所周知的典型症状。我们发现,用共平面多氯联苯3,4,5,3',4-五氯联苯(PenCB)处理豚鼠后,催化脂肪酸ω-羟基化的CYP4A1有显著诱导,尽管在处理过的大鼠中该细胞色素P450减少。过氧化物酶体具有与线粒体酶不同的β-氧化酶,在脂质代谢中也起重要作用。过氧化物酶体增殖剂已被证明在大鼠中通过相同机制调节CYP4A1和过氧化物酶体酶的表达。在本研究中,我们研究了PenCB处理对豚鼠肝脏过氧化物酶体酶的影响。结果,动物经PenCB处理后,肝脏过氧化物酶体的酶活性,如脂肪酸氧化系统、过氧化氢酶和尿酸氧化酶,有上升趋势。结果表明,豚鼠中过氧化物酶体酶和CYP4A1的调节也有关联,且PenCB对动物产生与过氧化物酶体增殖剂类似的作用。讨论了通过过氧化物酶体改变可能产生的毒性。