Drug metabolism in Octodon degus: low inductive effect of phenobarbital.
1. Differential effects of phenobarbital pre-treatment on liver microsomal drug metabolizing enzymes were registered in Octodon degus. 2. Glucuronidation reaction for morphine was decreased but that for p-nitrophenol was significantly increased. 3. Oxidative reactions such as naphthalene hydroxylation, morphine and aminopyrine N-demethylation were modestly increased. 4. In phenobarbital treated Octodon degus, testosterone metabolic pathways were decreased, not inducible or absent. 5. Spectral studies revealed two binding sites with different affinities for aniline in Octodon degus liver microsomes. 6. The poor phenobarbital induction on drug metabolism in Octodon degus may be a result of deficiency of androgen metabolic pathways associated to drug metabolizing enzymes.
Gaule
C
C
Department of Biochemistry, Faculty of Medicine, University of Chile, Santiago.
Vega
P
P
Sanchez
E
E
Del Villar
E
E
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009020:Morphine / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012377:Rodentia / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism
D000814:Aniline Compounds; D005965:Glucuronates; D009596:Nitrophenols; D004364:Pharmaceutical Preparations; D009020:Morphine; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C022724:testosterone 7-alpha-hydroxylase, hamster; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D014453:Glucuronosyltransferase; C023650:aniline; C024836:4-nitrophenol; D010634:Phenobarbital