Ornithine alpha-ketoglutarate counteracts the decrease of liver cytochromeP-450 content in burned rats

The effect of ornithine cu-ketoglutarate (OKG) on cytochrome P-450 enzyme a ctivities was studied in a well-defined model of injury (burn followed by f asting then subsequent hypocaloric diet) administered to young rats for 3 d . Hepatic microsomes were prepared by ultracentrifugation and levels of cyt ochromes P-450 were determined spectrophotometrically. The activities of et hoxy-resorufin-O-deethylase (EROD), benzyloxy-resorufin-O-dealkylase (BROD) , and erythromycin demethylase were measured as markers of P-450 LA, 2A, an d 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 n mol/mg microsomal proteins) was decreased by a hypocaloric diet (23%, P = 0 .003) and burn further enhanced this phenomenon (15%, P = 0.03). Both healt hy and burned rats receiving OKG showed the same level of cytochrome P-450 as the rats fed ad libitum. OKG supplementation counteracted the enhancemen t (40%) of EROD activity induced by hypocaloric diet but did not influence BROD and erythromycin demethylase activities. OKG sustained cytochrome P-45 0 levels in rats fed a hypocaloric diet, even after burning. These findings indicate that OKG may favor drug metabolism in this injured population. (C ) Elsevier Science Inc. 1999.