RT Journal Article
SR Electronic
T1 Cytochrome P450 Down-Regulation by Serum from Humans with a Viral Infection and from Rabbits with an Inflammatory Reaction
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1007
OP 1012
VO 29
IS 7
A1 Anne-Marie Bleau
A1 Caroline Fradette
A1 Ayman O. S. El-Kadi
A1 Marie-Claude Côté
A1 Patrick du Souich
YR 2001
UL http://dmd.aspetjournals.org/content/29/7/1007.abstract
AB Serum from humans with an upper respiratory viral infection (HSURVI) and from rabbits with a turpentine-induced acute inflammatory reaction (RSTIAR) 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 HSURVIand RSTIAR on P450 activity and expression following 24 h of incubation with hepatocytes from control (HCONT) and rabbits with a TIAR (HINFLA). RSTIAR incubated with HCONT for 24 h reduced P450 content and activity, and CYP3A6 by 45%, without changing CYP1A1 and 1A2; when incubated with HINFLA, RSTIAR decreased P450 content and activity without affecting CYP1A1 or 1A2. HSURVI incubated for 4 h with HCONT decreased P450 activity without affecting the amounts of CYP1A1, 1A2, or 3A6, although when incubated for 24 h, P450 activity and CYP3A6 amount decreased. HSURVI incubated with HINFLA 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 RSTIAR and HSURVI depends upon the susceptibility of the hepatocyte, i.e., HCONT or primed HINFLA; 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. The American Society for Pharmacology and Experimental Therapeutics