Effect of chondroitin sulfate on turpentine-induced down-regulation of CYP1A2 and CYP3A6.
This study aimed to assess whether chronic administration of chondroitin sulfate (CS) affects baseline expression of cytochrome P450 isoforms and impedes the decrease in expression and activity of CYP1A2 and CYP3A6 in rabbits with a turpentine-induced inflammatory reaction (TIIR). Seven groups of 5 rabbits, 3 control groups and 4 receiving 20 mg/kg/day of CS for 20 and 30 days, were used. The rabbits of 1 control group and 2 groups receiving CS had a TIIR; finally, the rabbits of one of the control groups remained in the animal facilities for 30 days to assess the effect of time and environment on cytochrome P450. In control rabbits, intake of CS for 20 and 30 days did not affect CYP3A6, CYP1A2 and NADPH cytochrome P450 reductase (CPR) mRNA, protein expression and activity. Compared with control rabbits, the TIIR not only reduced mRNA, protein expression and activity of CYP3A6 and CYP1A2 but also that of CPR. In rabbits with TIIR, CS prevented the decrease of CYP3A6 expression but not the reduction in activity. CS did not impede TIIR-induced down-regulation of CYP1A2. Hepatic NO() concentrations and NF-κB nuclear translocation were increased by the TIIR, effect reversed by CS. In vitro, in hepatocytes, CS did not alter the expression and activity of CYP3A6, CYP1A2, and CPR. In conclusion, oral CS elicits a systemic effect but does not affect CYP1A2, CYP3A6, and CPR in control rabbits, although in rabbits with TIIR, CS prevents CYP3A6 protein down-regulation but not that of CYP1A2.
Department of Pharmacology, Faculty of Medicine, University of Montréal, Montréal, Québec, Canada.
Mirela-Onita
MO
Iovu
Lucie
L
Héroux
Josep
J
Vergés
Eulália
E
Montell
Jacques
J
Paiement
Patrick
P
du Souich
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship; D014425:Turpentine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D002809:Chondroitin Sulfates; D001189:Aryl Hydrocarbon Hydroxylases; D019388:Cytochrome P-450 CYP1A2; C100638:cytochrome P-450 CYP3A6 (rabbit); D014425:Turpentine