The effect of Sudan III on drug metabolizing enzymes |
| |
Authors: | S Fujita J Peisach H Ohkawa Y Yoshida S Adachi T Uesugi M Suzuki T Suzuki |
| |
Affiliation: | 1. Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, NY 10461 U.S.A.;2. Department of Biopharmacy, Meiji College of Pharmacy, Setagaya-Ku, Tokyo, 154 Japan;3. Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Chiba 261 Japan |
| |
Abstract: | We have examined the induction of drug metabolizing enzymes in rat liver microsomes by azo dye, 1-(p-phenylazophenylazo)-2-naphthol (Sudan III). Marked increases were observed in the levels of cytochrome P-448 as well as in p-nitroanisole O-demethylase (p-NAD), amaranth (AR) and neoprontosil reductases (NPR) and 7-ethoxycoumarin O-deethylase (ECD) activities. On the other hand, aminopyrene N-demethylase activity was not significantly increased. Further, induced ECD activity was inhibited 90% by a specific antibody against cytochrome P-448 while the inhibition observed with an antibody against cytochrome P-450 was less than 25%. Simultaneous administration of Sudan III and 3-methylcholanthene (3-MC) induced cytochrome P-448 up to a level brought about by either Sudan III or 3-MC treatment alone. In contrast, Sudan III did not induce cytochrome P-448 in the 3-MC insensitive DBA/2 mouse. Solubilized microsomes from Sudan III-treated rats showed an identical sodium dodecyl sulfate polyacrylamide gel electrophoretic (SDS-PAGE) pattern with those from 3-MC-treated animals. It is concluded that the cytochrome P-448 induced in liver by Sudan III is very similar to that induced by 3-MC. Sudan III also induced UDP-glucuronyltransferase activity towards 1-naphthol and estradiol. It did not induce NADPH-cytochrome c reductase, nor any of the enzymes which constitute the microsomal electron transport chain except for cytochrome P-448. |
| |
Keywords: | Drug metabolism Induction Sudan III UDP-glucuronyltransferase APD AR amaranth reductase DMBA 7,12-dimethylbenzanthracene ECD 7-ethoxycoumarin . 3-MC 3-methylcholanthrene NPR neoprontosil reductase PB phenobarbital SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis Sudan III ZAH zoxazolamine hydroxylase |
本文献已被 ScienceDirect 等数据库收录! |
|