BIOCHEMICAL AND MORPHOLOGICAL-STUDIES OF AMMONIUM PERFLUOROOCTANOATE-INDUCED HEPATOMEGALY AND PEROXISOME PROLIFERATION
BIOCHEMICAL AND MORPHOLOGICAL-STUDIES OF AMMONIUM PERFLUOROOCTANOATE-INDUCED HEPATOMEGALY AND PEROXISOME PROLIFERATION
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DOI：
10.1016/0014-4800(87)90011-6
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发表时间：
1987-08-01
影响因子：
3.6
通讯作者：
GILLIES, PJ
中科院分区：
文献类型：
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作者：
PASTOOR, TP;LEE, KP;GILLIES, PJ
已知全氟辛酸铵(APFO)可引起大鼠显著的肝肿大。这些研究的目的是确定肝肿大的原因，并将其与其他扩大肝脏的化合物的效果进行比较。由于对照组和APFO组大鼠肝脏总DNA含量相似，肝肿大代表肥大反应，而不是增生性反应。APFO组大鼠肝脏细胞色素P-450含量和苯丙胺N-脱甲基酶活性升高，提示滑膜内质网增生。与膜结合酶相比，可溶性谷胱甘肽S转移酶和UDP葡萄糖醛酸基转移酶没有受到APFO处理的影响。APFO大鼠肝脏中肉碱乙酰转移酶相对肉碱棕榈酰基转移酶的活性不成比例地升高，证实了过氧化物体对线粒体的优势增殖。形态学研究证实，APFO处理的大鼠肝脏内质网、线粒体和过氧化物体均有增殖。与许多其他过氧化物酶增殖剂相比，APFO不具有降血脂活性。
Ammonium perfluorooctanoate (APFO) is known to induce a striking hepatomegaly in rats. The purpose of these studies was to determine the causes of the heptomegaly and compare the effect to other liver-enlarging compounds. Since the total hepatic DNA content was similar in control and APFO-treated rats, the hepatomegaly represented a hypertrophic rather than a hyperplastic response. The cytochrome P-450 content and activity of benzphetamine N-demethylase increased in the livers of APFO-treated rats, indicating the proliferation of the smooth endoplasmic reticulum. In contrast to the membrane-bound enzymes, the soluble enzymes glutathione S-transferase and UDPglucuronyltransferase were unaffected by APFO treatment. The activity of carnitine acetyltransferase was disproportionately increased relative to carnitine palmitoyltransferase in the livers of APFO vs that in control rats, confirming the predominant proliferation of peroxisomes vs that of mitochondria. Morphological studies confirmed the proliferation of the endoplasmic reticulum, mitochondria, and peroxisomes in the livers of APFO-treated rats. In contrast to many other peroxisome proliferating agents, APFO did not possess hypolipidemic activity.