Immunohistochemical properties of dipyrone-induced cytochromes P450 in rats.
1. Rat hepatic cytochrome P450s induced by dipyrone were studied enzymatically, immunochemically and immunohistochemically. 2. Dipyrone administered to male Wistar rats increased pentoxyresorufin O-depentylation (PROD), ethoxyresorufin O-deethylation (EROD) and 7-ethoxycoumarin O-deethylation (ECOD) activities up to 44-, 1.9-, and 2.6-fold, respectively. Aryl hydrocarbon hydroxylase (AHH) activity was not affected. 3. Immunoinhibition with the monoclonal antibody (Mab) 2-66-3 (to CYP2B1/2) markedly decreased PROD and EROD activities, but not AHH activity. The Mab 1-7-1 (to CYP1A1/2) was without effect. 4. Histochemically, the Mab 2-66-3 gave a strong and uniform staining in livers from dipyrone-treated rats, whereas the Mab 1-7-1 gave a positive reaction in a narrow perivenous strip. 5. The induction pattern as well as inhibition by the Mabs convincingly demonstrate the predominant production of CYP2B1/2 in the induction spectrum of dipyrone. The increase in enzyme activities other than PROD may be due to the overlapping substrate specificity of CYP2B1/2 enzymes. The immunohistochemical analysis also indicated the participation of CYP1A1/2.
Kraul
H
H
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Pasanen
M
M
Sigusch
H
H
Stenbäck
F
F
Park
S S
SS
Gelboin
H V
HV
Pelkonen
O
O
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004177:Dipyrone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065607:Cytochrome P-450 Enzyme Inhibitors; D004177:Dipyrone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010634:Phenobarbital