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Alteration of methylcholanthrene-mediated suppression of cutaneous delayed hypersensitivity by benzoflavone treatment of C57BL/6J mice.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 1988 Aug; Vol. 95 (1), pp. 72-81. - Publication Year :
- 1988
-
Abstract
- The potential role of the cytochromes P-450 in methylcholanthrene (MC)-mediated suppression of cutaneous delayed hypersensitivity (CDH) in C57BL/6J (B6) mice was evaluated indirectly by treating mice with agents known to induce or inhibit hepatic cytochromes P-450 prior to contact sensitization. Subsequent alterations in aryl hydrocarbon hydroxylase (AHH) activity and CDH, as measured by suppression of 2,4-dinitrofluorobenzene (DNFB)-induced ear swelling, were measured. MC administration resulted in a dose-dependent suppression of ear swelling and a concomitant dose-dependent induction of hepatic AHH activity. Treatment of B6 mice with phenobarbital (PB), 80 mg/kg daily X 3, a broad spectrum inducer of P-450, resulted in a 2.5-fold increase in benzo[a]pyrene (B[a]P) hydroxylase activity without affecting CDH. Animals treated with the same PB protocol prior to an ED20 dose of MC showed no difference in suppression of CDH compared to animals treated with MC alone. In contrast, successive treatment with the selective P1-450 inducer, 5,6-benzoflavone (beta NF), prior to and following an ED20 dose of MC significantly increased suppression of CDH (p less than 0.001) usually seen at this MC dose. Treatment with a known inhibitor of cytochrome P1-450 activity, 7,8-benzoflavone (alpha NF), did not prevent AHH induction when administered prior to and following MC (ED100) nor did it suppress CDH when administered alone. However, this alpha NF treatment completely prevented suppression of CDH usually seen at this MC dose. These data provide evidence suggesting that metabolic activation by cytochrome P1-450 is required for the expression of the immunosuppressive activity of MC.
- Subjects :
- Animals
Aryl Hydrocarbon Hydroxylases metabolism
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System metabolism
Dinitrofluorobenzene immunology
Dose-Response Relationship, Drug
Drug Hypersensitivity prevention & control
Enzyme Induction drug effects
Female
Liver drug effects
Liver enzymology
Male
Mice
Mice, Inbred C57BL
Phenobarbital pharmacology
Polycyclic Compounds metabolism
Receptors, Aryl Hydrocarbon
Receptors, Drug metabolism
beta-Naphthoflavone
Benzoflavones pharmacology
Flavonoids pharmacology
Hypersensitivity, Delayed prevention & control
Immunosuppressive Agents antagonists & inhibitors
Methylcholanthrene antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0041-008X
- Volume :
- 95
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 2842891
- Full Text :
- https://doi.org/10.1016/s0041-008x(88)80009-7