HEPATIC PHASE-I AND PHASE-II BIOTRANSFORMATIONS IN QUAIL AND TROUT - COMPARISON TO OTHER SPECIES COMMONLY USED IN TOXICITY TESTING
HEPATIC PHASE-I AND PHASE-II BIOTRANSFORMATIONS IN QUAIL AND TROUT - COMPARISON TO OTHER SPECIES COMMONLY USED IN TOXICITY TESTING
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DOI：
10.1016/0041-008x(83)90327-7
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发表时间：
1983-01-01
影响因子：
3.8
通讯作者：
KLAASSEN, CD
中科院分区：
文献类型：
--
作者：
GREGUS, Z;WATKINS, JB;KLAASSEN, CD
研究了鹌鹑和鳟鱼进行一系列具有代表性的第一阶段和第二阶段生物转化的能力。为了便于物种间比较，我们在相同的条件下同时检测了大鼠、小鼠、家兔、豚鼠、猫和狗对相同底物的代谢。两种非哺乳动物都能代谢4种具有代表性的第一期混合功能氧化酶底物和1种环氧化物水解酶底物，但活性往往低于哺乳动物。还注意到共轭途径的重要差异。在这些差异中，鹌鹑的谷胱甘肽结合能力相对不足，而鳟鱼的硫酸盐化合物结合能力较低。鳟鱼肝脏对睾酮和胆红素的udp -葡萄糖醛酸转移酶活性显著高，而鹌鹑肝脏形成萘酚、对硝基酚和洋地黄苷-单洋地黄苷的葡萄糖醛酸苷。同样值得注意的是，鹌鹑和鳟鱼对异烟肼的n -乙酰转移酶活性很高。-萘胺和2-氨基芴。在一个给定的酶途径的底物特异性的差异可能已经表明，多种形式的药物代谢系统也发生在这些非哺乳动物物种。在相同条件下，不同物种对某些底物的酶活性存在数百或数千倍的差异，这再次强调了在从一个物种到另一个物种的异种代谢外推时需要谨慎。
The ability of quail and trout to perform a number of representative phase 1 and phase 2 biotransformations was examined. To facilitate interspecies comparisons, metabolism of the same substrates was examined simultaneously under uniform conditions for rat, mouse, rabbit, guinea pig, cat and dog. Both nonmammalian species metabolized 4 representative substrates of phase 1 mixed-function oxidases and 1 substrate of epoxide hydrolase, although activity tended to be lower than that of the mammals. Important differences in the conjugative pathways were also noted. Among these differences were the quail''s relative deficiency in glutathione conjugation and the trout''s low ability to conjugate sulfate compounds. Trout liver UDP-glucuronosyltransferase activity was remarkably high toward testosterone and bilirubin, while quail liver formed glucuronides of naphthol, p-nitrophenol and digitoxigenin-monodigitoxoside. Also noteworthy was the high N-acetyltransferase activity of quail and trout toward isoniazid, .beta.-naphthylamine and 2-aminofluorene. Differences in substrate specificity for a given enzymatic pathway may have been an indication that multiple forms of drug metabolizing systems also occurred in these nonmammalian species. Observation of several hundred- or thousand-fold differences between species in their enzyme activities for certain substrates under uniform conditions reemphasized the need for caution in extrapolation of xenobiotic metabolism from 1 sp. to another.