Haasch M L, Henderson M C, Buhler D R
University of Maryland, Chesapeake Biological Laboratory, Solomons, MD 20688-0038, USA.
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Nov;121(1-3):297-303. doi: 10.1016/s0742-8413(98)10050-6.
In mammals, sensitivity to peroxisome proliferation by peroxisome proliferating agents (PPAs) appears to be correlated with inducibility of lauric acid hydroxylase activity. Bluegill and catfish have been shown to respond to PPAs by induction of lauric acid hydroxylase immunoreactive proteins (Haasch, 1996). In this investigation, induction of lauric acid hydroxylase activity was confirmed by HPLC and mass spectral analysis of specific hydroxylation products and possible species-specific differences in metabolism were investigated. Male bluegill, channel catfish and rat, were administered the model PPAs, clofibrate (200 mg kg-1, i.p.), ciprofibrate (100 mg kg-1, i.p.), or olive oil as vehicle control (both sexes of catfish), 48 h prior to hepatic, trunk kidney (catfish only) or kidney (rat) microsome preparation. In general, total metabolism of lauric acid was similar in all species, but female catfish metabolize lauric acid to a greater extent than males. Ciprofibrate treatment produced significant induction of omega- and omega-6 hydroxylation in male catfish kidney. In male bluegill liver, omega-, omega-4 and omega-5 hydroxylations were significantly induced by clofibrate treatment. The data indicate that induction of lauric acid hydroxylase cytochrome(s) P450 occurs in PPA-exposed fish which may be a consideration for environmentally-exposed responsive species.
在哺乳动物中，对过氧化物酶体增殖剂（PPAs）的过氧化物酶体增殖敏感性似乎与月桂酸羟化酶活性的诱导性相关。已证明蓝鳃太阳鱼和鲶鱼对PPAs的反应是诱导月桂酸羟化酶免疫反应蛋白（哈施，1996年）。在本研究中，通过对特定羟基化产物的高效液相色谱法和质谱分析证实了月桂酸羟化酶活性的诱导，并研究了可能的物种特异性代谢差异。雄性蓝鳃太阳鱼、沟鲶和大鼠在制备肝、躯干肾（仅鲶鱼）或肾（大鼠）微粒体前48小时，分别给予模型PPAs氯贝丁酯（200毫克/千克，腹腔注射）、环丙贝特（100毫克/千克，腹腔注射）或作为溶剂对照的橄榄油（鲶鱼雌雄均用）。总体而言，所有物种中月桂酸的总代谢情况相似，但雌性鲶鱼对月桂酸的代谢程度高于雄性。环丙贝特处理在雄性鲶鱼肾脏中显著诱导了ω-和ω-6羟基化。在雄性蓝鳃太阳鱼肝脏中，氯贝丁酯处理显著诱导了ω-、ω-4和ω-5羟基化。数据表明，在暴露于PPA的鱼类中发生了月桂酸羟化酶细胞色素P450的诱导，这可能是环境暴露敏感物种需要考虑的因素。
