Ornithine alpha-ketoglutarate counteracts the decrease of liver cytochrome P-450 content in burned rats.
The effect of ornithine alpha-ketoglutarate (OKG) on cytochrome P-450 enzyme activities was studied in a well-defined model of injury (burn followed by fasting then subsequent hypocaloric diet) administered to young rats for 3 d. Hepatic microsomes were prepared by ultracentrifugation and levels of cytochromes P-450 were determined spectrophotometrically. The activities of ethoxy-resorufin-O-deethylase (EROD), benzyloxy-resorufin-O-dealkylase (BROD), and erythromycin demethylase were measured as markers of P-450 1A, 2A, and 3A isotypes respectively. The level of total hepatic microsomal proteins (8 mg/mL) remained constant. The level of cytochrome P-450 (1.14+/-0.08 nmol/mg microsomal proteins) was decreased by a hypocaloric diet (23%, P = 0.003) and burn further enhanced this phenomenon (15%, P = 0.03). Both healthy and burned rats receiving OKG showed the same level of cytochrome P-450 as the rats fed ad libitum. OKG supplementation counteracted the enhancement (40%) of EROD activity induced by hypocaloric diet but did not influence BROD and erythromycin demethylase activities. OKG sustained cytochrome P-450 levels in rats fed a hypocaloric diet, even after burning. These findings indicate that OKG may favor drug metabolism in this injured population.
Roch-Arveiller
M
M
Département de Pharmacologie, Hôpital Cochin, Paris, France.
Fontagné
J
J
Coudray-Lucas
C
C
Le Boucher
J
J
Cynober
L
L
Muntaner
O
O
Delaforge
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002056:Burns / Q000188:drug therapy* / Q000201:enzymology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D002149:Energy Intake; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009952:Ornithine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C002118:ornithine alpha-ketoglutarate; D003577:Cytochrome P-450 Enzyme System; D009952:Ornithine; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating