Cytochrome P450 Down-Regulation by Serum from Humans with a Viral Infection and from Rabbits with an Inflammatory Reaction

• Published in: Drug metabolism and disposition Vol. 29; no. 7; pp. 1007 - 1012
• Main Authors: BLEAU, Anne-Marie, FRADETTE, Caroline, EL-KADI, Ayman O. S, COTE, Marie-Claude, DU SOUICH, Patrick
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.07.2001
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Blood; Cytochrome P-450 Enzyme System - metabolism; Down-Regulation; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Inflammation - blood; Inflammation - enzymology; Male; Oxidoreductases; Rabbits; Respiratory Tract Infections - blood; Respiratory Tract Infections - enzymology; Virus Diseases - blood; Virus Diseases - enzymology; Human; Digestive system; Isozyme; Cytochrome P450; Liver; Rabbit; Inflammation; Lagomorpha; In vitro; Infection; Vertebrata; Mammalia; Enzymatic activity; Hepatocyte; Animal; Viral disease; Serum
• ISSN: 0090-9556; 1521-009X

Serum from humans with an upper respiratory viral infection (HS URVI ) and from rabbits with a turpentine-induced acute inflammatory reaction (RS TIAR ) reduces the activity of hepatic cytochrome P450 (P450) following 4 h of incubation. The aim of the present study was to assess the effect of HS URVI and RS TIAR on P450 activity and expression following 24 h of incubation with hepatocytes from control (H CONT ) and rabbits with a TIAR (H INFLA ). RS TIAR incubated with H CONT for 24 h reduced P450 content and activity, and CYP3A6 by 45%, without changing CYP1A1 and 1A2; when incubated with H INFLA , RS TIAR decreased P450 content and activity without affecting CYP1A1 or 1A2. HS URVI incubated for 4 h with H CONT decreased P450 activity without affecting the amounts of CYP1A1, 1A2, or 3A6, although when incubated for 24 h, P450 activity and CYP3A6 amount decreased. HS URVI incubated with H INFLA for 4 h reduced P450 content and activity, and incubated for 24 h reduced activity, P450 content, and amount of CYP1A1 and 1A2 proteins. The present study demonstrates that 1) the effect of RS TIAR and HS URVI depends upon the susceptibility of the hepatocyte, i.e., H CONT or primed H INFLA ; 2) P450 down-regulation is preceded by a decrease in P450 activity; 3) the nature of the inflammatory reaction determines the repercussions on P450 activity and expression; and 4) CYP3A6 is more vulnerable than CYP1A1 and 1A2 to the down-regulation provoked by an inflammatory challenge.