Absence of P450 effect with a novel phospholipid emulsion (GR270773)

Abstract

GR270773 (773) is a novel phospholipid emulsion with endotoxin binding activity. Alterations in dietary lipids have been shown to alter P450 activity. We therefore examined 773′s effects on protein content and activity of selected hepatic P450 enzymes in male rats. 773 was given intravenously by continuous infusion to three male rats/group at doses of 0, 800, and 1600 mg/kg/day for 3 days. Two hours after the infusion, liver samples were removed, frozen, and stored at -60C. Microsomal fractions were prepared for each animal by differential centrifugation. Protein yield, total P450 content, and activities of 7-ethoxyresorufin O-deethylase (CYP1A), testosterone 6β- and 16β-hydroxylase (CYP3A and CYP2B, respectively), and lauric acid 11- and 12-hydroxylase (CYP2E and CYP4A, respectively) were examined. Treatment with 773 at doses of 800 and 1600 mg/kg/day for 3 days caused no notable changes in the mean hepatic microsomal protein yields (p>0.8) and total cytochrome P450 content (p>0.3). Treatment of male rats with 773 caused no notable change in the mean activity of CYP1A, CYP3A or CYP4A (p>0.4). Treatment with 773 caused a slight non-significant (p>0.2) increase in the mean activities of CYP2B and CYP2E in the 1600-mg/kg/day dose group (1.6 and 1.4-times control, respectively). Intravenous infusion of 773 at 800 and 1600 mg/kg/day for 3 days to male rats had no notable effect on hepatic microsomal protein, total cytochrome P450 levels or the activities of 5 P450 subfamilies. Clinical Pharmacology & Therapeutics (2004) 75, P87–P87; doi: 10.1016/j.clpt.2003.11.333