Reinke L A, Sexter S H, Rikans L E
Res Commun Chem Pathol Pharmacol. 1985 Jan;47(1):97-106.
Ethanol and imidazole have been shown to cause similar changes in the hepatic drug metabolizing enzymes of rabbit liver. The effects of these agents on hepatic monooxygenase activities were compared in the rat to test whether similar changes might also occur in this species. Ethanol feeding caused 4- to 5-fold increases in rates of the microsomal metabolism of aniline and p-nitrophenol, and smaller increases in rates of dealkylation of 7-ethoxycoumarin and aminopyrine. Ethanol doubled cytochrome P-450 content and increased the staining intensity of a polypeptide with an apparent molecular weight of 54,000 as determined by SDS polyacrylamide gel electrophoresis. Imidazole pretreatment also enhanced rates of the microsomal metabolism of 7-ethoxycoumarin and aminopyrine, but did not affect rates of aniline or p-nitrophenol hydroxylation. In addition, imidazole did not affect cytochrome P-450 content or the electrophoretic profile of microsomal polypeptides. Thus, the effects of ethanol and imidazole pretreatments on hepatic drug metabolism vary substantially between rabbits and rats.
乙醇和咪唑已被证明会使兔肝脏中的肝药代谢酶发生类似变化。在大鼠中比较了这些药物对肝单加氧酶活性的影响，以测试在该物种中是否也可能发生类似变化。喂食乙醇导致苯胺和对硝基苯酚的微粒体代谢速率增加4至5倍，7-乙氧基香豆素和氨基比林的脱烷基化速率增加幅度较小。乙醇使细胞色素P-450含量增加一倍，并增加了通过SDS聚丙烯酰胺凝胶电泳测定的表观分子量为54,000的一种多肽的染色强度。咪唑预处理也提高了7-乙氧基香豆素和氨基比林的微粒体代谢速率，但不影响苯胺或对硝基苯酚的羟化速率。此外，咪唑不影响细胞色素P-450含量或微粒体多肽的电泳图谱。因此，乙醇和咪唑预处理对肝药代谢的影响在兔和大鼠之间有很大差异。
