Influence of urethane and ketamine on rat hepatic cytochrome P450 in vivo.
The aim of this study was to identify the effects of widely used laboratory anaesthetics on cytochrome (CYP) activity in male Sprague Dawley rats in vivo. The anaesthetics used were urethane and ketamine. 7-Ethoxyresorufin (EROD), 7-pentoxyresorufin (PROD), aniline and ethylmorphine were used as substrates for CYP 1A, CYP 2B, CYP 2E1 and CYP 3A, respectively. Urethane increased EROD (CYP 1A) activity by 40 % (p < 0.01), and hydroxylation of aniline (CYP 2E1) by 14 % in the early phase of anaesthesia and by 60 % (p < 0.01) in the later one. Urethane also reduced the demethylation of ethylmorphine by 37 % (p < 0.01), but did not affect CYP 2B activity significantly. Ketamine did not significantly affect CYP 1A, 2B or 2E1. However, it reduced the demethylation of ethylmorphine (i.e. CYP 3A) by 32 % (p < 0.01). From these data, we concluded that a single dose of urethane inhibits CYP 3A but increases CYP 2E1 and CYP 1A, and that a single dose of ketamine inhibits the activity of CYP 3A.
Meneguz
A
A
Department of Biochemical Pharmacology, Istituto Superiore di Sanità, Roma, Italia.
Fortuna
S
S
Lorenzini
P
P
Volpe
M T
MT
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014520:Urethane / Q000494:pharmacology*
D000777:Anesthetics; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D014520:Urethane; D007649:Ketamine; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating