Mixed-function oxidase system induction and propylene hepatotoxicity.
Mixed-function oxidase system induction and propylene hepatotoxicity.
复制标题
混合功能氧化酶系统诱导和丙烯肝毒性。
DOI：
10.1080/15287398509530634
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Conolly,RB
中科院分区：
文献类型：
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作者：
Osimitz,TG;Conolly,RB
丙烯对经多氯联苯（PCB：Aroclor 1254）预处理的雄性Charles River COBS Sprague道利大鼠具有肝毒性。吸入暴露于50，000 ppm丙烯4小时后，PCB预处理大鼠的肝重/体重比增加，血清酶活性升高。在丙烯暴露期间，PCB预处理大鼠的肝微粒体细胞色素P-450含量显著下降，并持续至少24小时。此外，PCB预处理的丙烯暴露大鼠肝微粒体苯胺羟化酶的比活性降低。然而，肝微粒体氨基比林脱甲基酶或葡萄糖-6-磷酸酶的活性没有变化。用对萘酮（BNF）、苯巴比妥（PB）或BNF和PB的混合物预处理的大鼠的丙烯暴露没有肝毒性。然而，在这些动物中，丙烯暴露开始后24 h，肝微粒体细胞色素P-450水平大幅下降。因此，导致肝细胞色素P-450破坏的丙烯依赖性过程与导致急性肝毒性的过程在质和量上是不同的。暴露前禁食对PCB预处理大鼠暴露于50，000 ppm丙烯4 h所导致的肝毒性没有影响。在暴露于丙烯之前立即对PCB预处理的大鼠给予SKF-525 A可完全防止血清酶活性和肝重/体重比升高。或PCB预处理大鼠，空气中含有20%丙烯/80%这些结果表明，PCB预处理是丙烯在大鼠肝毒性的先决条件。丙烯的细胞色素P-450依赖性生物活化与这种肝毒性相关，但需要进一步研究来表征PCB-丙烯相互作用的机制。
Propylene is hepatotoxic to male Charles River COBS Sprague‐Dawley rats pretreated with polychlorinated biphenyls (PCB: Aroclor 1254). Four‐hour inhalation exposure to 50,000 ppm propylene increased liver weight/body weight ratios and elevated serum enzyme activities in PCB‐pretreated animals.Hepatic microsomal cytochrome P‐450 content of PCB‐pretreated rats dropped profoundly during propylene exposure and remained depressed for at least 24 h. In addition, PCB‐pretreated, propylene‐exposed rats exhibited a decrease in the specific activity of hepatic microsomal aniline hydroxylase. However, there was no change in activities of either hepatic microsomal aminopyrine demethylase or glucose‐6‐phosphatase.Propylene exposure of rats pretreated with p‐naphthoflavone (BNF), phenobarbital (PB), or a mixture of BNF and PB was not hepatotoxic. However, there was, in these animals, a substantial decline in hepatic microsomal cytochrome P‐450 levels 24 h after the start of propylene exposure. Hence, the propylene‐dependent process resulting in hepatic cytochrome P‐450 destruction is qualitatively or quantitatively different from the process that causes acute hepatotoxicity.Preexposure fasting had no effect on the hepatotoxicity resulting from a 4‐h exposure of PCB‐pretreated rats to 50,000 ppm propylene. Administration of SKF‐525A to PCB‐pretreated rats immediately prior to propylene exposure completely prevented elevations in serum enzyme activities and liver weight/body weight ratios.In vitroincubation of hepatic microsomes prepared from either BNF‐, PB‐, or PCB‐pretreated rats with an atmosphere of 20% propylene/80% air produced in NADPH‐dependent decrease in cytochrome P‐450 content.These results suggest that PCB pretreatment is a prerequisite for propylene hepatotoxicity in the rat. Cytochrome P‐450‐dependent bioactivation of propylene is associated with this hepatotoxicity, but further studies are needed to characterize the mechanism of the PCB‐propylene interaction.