Effect of adjuvant-induced arthritis on hepatic drug metabolism in rats.
1. Hepatic drug metabolism was investigated in normal, adjuvant-induced arthritic (AA), indomethacin-treated AA and prednisolone-treated AA rats. The contents of P450 and b5 and the activities of NADH-b5 reductase (fp2), NADPH-ferrihaemoprotein reductase, P450 mixed function oxidase, FAD-monooxygenase and several enzymes involved in conjugation were remarkably lower in AA than in normal rats. 2. Many of the decreased enzyme activities were restored to normal levels by the continuous administration (3 weeks) of indomethacin or prednisolone, which improved the arthritic states of the animals. However, the restoration of FAD-monooxygenase activity by the administration of indomethacin or prednisolone was incomplete. The P450 and b5 contents and the fp2 activity in prednisolone-treated AA rats were also significantly lower than those in normal rats. 3. These findings indicate that the ability of the liver to metabolize drugs (both oxidation and conjugation) in AA rats is greatly decreased and that a long series of the treatment of AA rats with anti-inflammatory drugs is required to restore several enzyme activities.
Faculty of Pharmaceutical Science, Fukuoka University, Japan.
A
A
Toda
N
N
Ishii
T
T
Kihara
A
A
Nagamatsu
H
H
Shimeno
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000201:enzymology*; D015239:Arylsulfotransferase / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D003579:Cytochrome Reductases / Q000187:drug effects / Q000378:metabolism; D042966:Cytochrome-B(5) Reductase; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000187:drug effects / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000187:drug effects / Q000378:metabolism; D010105:Oxygenases / Q000187:drug effects / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D011239:Prednisolone; D006899:Mixed Function Oxygenases; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase; D015239:Arylsulfotransferase; D007213:Indomethacin