The possible role of the ethanol-inducible isozyme of cytochrome P450 in the metabolism and distribution of carbon disulfide.
The possible role of the ethanol-inducible isozyme of cytochrome P450 in the metabolism and distribution of carbon disulfide.
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细胞色素 P450 乙醇诱导同工酶在二硫化碳代谢和分布中的可能作用。
DOI：
10.1016/0041-008x(88)90021-x
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发表时间：
1988
影响因子：
3.8
通讯作者：
Rubin,RJ
中科院分区：
文献类型：
--
作者：
Snyderwine,EG;Kroll,R;Rubin,RJ
用乙醇和其他醇进行急性治疗已被证明会增强某些外源性药物的肝毒性，部分原因是通过诱导混合功能氧化酶（MFO）系统。二硫化碳（CS2）诱导的肝毒性和MFO系统的抑制已被证明是MFO代谢的结果。本研究考察了几种不同醇诱导大鼠肝内多酚代谢cs2的能力，以及这种诱导对cs2分布和肝毒性的影响。在给药18小时后（1 2ld50剂量，po），经异丙醇、甲醇和乙醇预处理后，cs2微粒体MFO代谢显著增强（按效力递减的顺序），但经异丁醇预处理后则无此作用。不同醇对cs2代谢的增强程度与硝基苯甲醚o -去甲基化和苯胺羟基化的增强程度平行，MFO活性与细胞色素P450乙醇诱导同工酶相关。CS2（1 mg/kg， 1小时，3小时）仅抑制酒精预处理增强的细胞色素p450介导的活性。这些结果表明，cs2的代谢是由乙醇诱导同工酶催化的。在给药后3小时（1 mg/kg, ip），酒精诱导的大鼠肝脏中14cs2衍生的放射性明显高于对照和异丁醇预处理的大鼠。然而，只有甲醇预处理导致血浆、脑和肾脏中14cs2衍生放射性的保留增加。与其他酒精预处理不同，甲醇减少了cs2给药后3小时内的总14c，并导致血浆谷丙转氨酶显著（两倍）增加，在cs2暴露后24小时测量（625 mg/kg）。这些数据表明，酒精诱导mfo依赖性cs2代谢本身并不足以导致cs2诱导的肝损伤，尽管它确实会导致特异性细胞色素p450功能的丧失。
Acute treatment with ethanol and other alcohols has been shown to potentiate the hepatotoxicity of certain xenobiotics, in part via induction of the mixed-function oxidase (MFO) system. Carbon disulfide (CS2)-induced hepatotoxicity and inhibition of the MFO system have been shown to be a consequence of MFO metabolism. In the present study, the ability of several different alcohols to induce the hepatic MFO metabolism of CS2and the effects of this induction on CS2distribution and hepatotoxicity were examined in rats. Eighteen hours after alcohol administration (1 2 LD50 dose, po), CS2microsomal MFO metabolism was significantly enhanced, in order of descending potency, by isopropanol, methanol, and ethanol pretreatments, but not by isobutanol pretreatment. The degree of enhancement of CS2metabolism by different alcohols paralleled the enhancement of nitroanisole O-demethylation and aniline hydroxylation, MFO activities associated with the ethanol-inducible isozyme of cytochrome P450. CS2(1 mg/kg, ip, 3 hr) inhibited only the cytochrome P450-mediated activities enhanced by alcohol pretreatment. These results suggest that CS2metabolism is catalyzed by the ethanol-inducible isozyme. Alcohol-induced rats had significantly more14CS2-derived radioactivity in the liver than control and isobutanol-pretreated rats 3 hr after dosing (1 mg/kg, ip). However, only methanol pretreatment resulted in an increased retention of14CS2-derived radioactivity in plasma, brain, and kidney. Unlike other alcohol pretreatments, methanol decreased the total14C expired during the 3-hr period after CS2dosing and caused a significant (twofold) increase in plasma glutamic-pyruvic transaminase, measured 24 hr after CS2exposure (625 mg/kg). These data indicate that alcohol induction of MFO-dependent CS2metabolism per se is not sufficient to result in CS2-induced hepatic damage although it does lead to loss of specific cytochrome P450function.
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乙醇和异烟肼诱导肝微粒体细胞色素 P-450 依赖性活性，其对底物和抑制剂具有相似的特性，但与经典诱导剂诱导的特性不同。
影响因子：
5.8
作者：
G. Gadeholt
通讯作者：
G. Gadeholt
影响因子：
2.9
作者：
GUENGERICH, FP;DANNAN, GA;KAMINSKY, LS
通讯作者：
KAMINSKY, LS
化学工人的孤立性肝损伤。
DOI：
10.1136/oem.41.1.142
发表时间：
1984
期刊：
British Journal of Industrial Medicine
影响因子：
--
作者：
M. Døssing;L. Ranek
通讯作者：
L. Ranek
酒精摄入对大鼠慢性暴露于二硫化碳引起的某些紊乱的影响。
影响因子：
3.5
作者：
J. Opacka;T. Wrónska;J. Ko;Kołakowski;B. Opalska
通讯作者：
B. Opalska
异丙醇增强细胞色素 P-450 依赖性单加氧酶活性及其对四氯化碳中毒的影响。
影响因子：
3.8
作者：
T. Ueng;L. Moore;R. Elves;A. Alvares
通讯作者：
A. Alvares