Cytochrome P450 down-regulation by serum from humans with a viral infection and from rabbits with an inflammatory reaction.
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.
Bleau
A M
AM
Department of Pharmacology, Faculty of Medicine, University of Montréal, Montréal, Québec, Canada.
Fradette
C
C
El-Kadi
A O
AO
Côté
M C
MC
du Souich
P
P
D000818:Animals; D001769:Blood; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000201:enzymology; D008297:Male; D011817:Rabbits; D012141:Respiratory Tract Infections / Q000097:blood* / Q000201:enzymology; D014777:Virus Diseases / Q000097:blood* / Q000201:enzymology
D003577:Cytochrome P-450 Enzyme System