Species and sex differences of testosterone and nifedipine oxidation in liver microsomes of rat, dog and monkey
| Autor: | A. Togawa, T Hata, Z Tozuka, Toshiro Niwa, Y. Naritomi, T Shiraga, H Kaneko, Kazuhide Iwasaki |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Nifedipine Health Toxicology and Mutagenesis Biology In Vitro Techniques Toxicology Hydroxylation Biochemistry Isozyme Rats Sprague-Dawley chemistry.chemical_compound Dogs Cytochrome P-450 Enzyme System Species Specificity Internal medicine medicine Animals Testosterone Androstenedione Pharmacology Sex Characteristics General Medicine Metabolism biology.organism_classification Calcium Channel Blockers Rats Isoenzymes Macaca fascicularis Endocrinology chemistry Microsoma Enzyme Induction Steroid Hydroxylases Microsome Microsomes Liver Female Aryl Hydrocarbon Hydroxylases Oxidation-Reduction medicine.drug |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 25(10) |
| ISSN: | 0049-8254 |
| Popis: | 1. Species and sex differences in testosterone hydroxylation and nifedipine oxidation in liver microsomes from rat, dog and monkey have been investigated. 2. The formation of 2 alpha-, 2 beta-, 6 beta-, and 16 alpha-hydroxytestosterone and androstenedione in the male rat was higher than that in the female rat. Microsomes prepared from the male rat oxidized nifedipine about eight times faster than did those from the female rat. In contrast, marked sex-related differences were not seen in the dog and monkey. 3. Nifedipine oxidase activity in rat, dog and monkey correlated significantly with the activities for both testosterone 2 beta-hydroxylation and 6 beta-hydroxylation, suggesting the involvement of P4503A isozymes in these reactions. The ratios of formation of the 2 beta- to 6 beta-hydroxytestosterone in male rat and monkey were 0.17 and 0.18 respectively, whereas that in dog was 0.46. The corresponding activity ratios catalysed by P450DPB-1, a P4503A isoform purified from dog liver microsomes, was 0.36. 4. The formation of 16 beta-hydroxytestosterone was higher than that of the 16 alpha-hydrolated metabolite in liver microsomes from monkey, whereas 16 alpha-hydroxytestosterone was the predominant metabolite in the rat and dog, indicating species differences in stereoselectivity at the 16-position. |
| Databáze: | OpenAIRE |
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