Effect of induction of T-cell-dependent antibody with sheep red blood cells on P-450-dependent and -independent xenobiotic metabolizing enzymes.
The effect of an antigenic challenge with sheep red blood cells (SRBC) on the activities of cytochrome P-450-dependent and -independent xenobiotic metabolizing enzymes and on lipid peroxidation in the liver was investigated. The studies were carried out using three mouse strains of C57B1/10 and three strains of C3H backgrounds which are cogenic, differing genetically at the H-2 complex. The basal levels of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-deethylase (7-Ec) were different among congenic strains. The activity of 7-Ec was lower in C3H background mice than in B10 background mice. Similarly, the difference due to the strain and the H-2 locus was detected in the activities of P-450-independent enzymes such as malathion and diethyl succinate carboxylesterases, glutathione S-transferase, and epoxide hydrolases in microsomal and cytosolic fractions. The degree of immune responsiveness in these mice was determined by a plaque forming cell assay. Within the same background, the H-2b mouse strain was a high responder and the H-2k a low responder to SRBC. However, treatment with SRBC had no significant depressive effect on P-450-dependent enzyme activities except in C3H/He. Activity of AHH was suppressed in C3H/He mice. Treatment with SRBC had no effect on P-450-independent enzyme activities except for malathion carboxylesterase: the activity was increased in C3H/He and C3H.JK, whereas it was decreased in B10. The basal level of lipid peroxidation was lower in C3H/He and C3H.JK. The treatment produced a significant enhancement in lipid peroxidation in C3H/He, B10 and B10.BR (P less than 0.05) with a concomitant increase in xanthine oxidase activity (P less than 0.05). Thus, the present study revealed that a specific antigenic challenge, unlike non-specific immunostimulants (e.g. poly IC, endotoxin), does not necessarily inhibit P-450-dependent xenobiotic metabolizing enzymes even though antigen challenge increased XO activity and lipid peroxidation. The possible roles of an increase in lipid peroxidation and xanthine oxidase activity in immune response to SRBC and xenobiotic metabolizing enzymes are discussed.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D000917:Antibody Formation; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology*; D007114:Immunization; D007527:Isoenzymes / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014969:Xanthine Oxidase / Q000378:metabolism
D007527:Isoenzymes; D008054:Lipid Peroxides; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; D014969:Xanthine Oxidase