2.3.7.8-Tetrachlorodibenzo-p-Dioxin Induced Immunosuppression: Its Possible Alteration by In Vivo Administration of Specific Hepatic Enzyme Inducers.

Abstract : The possible alterations of TCDD toxicity induced by treatments with cytochrome P-450 inducers have been investigated in mice. TCDD toxicity has been evaluated in terms of immunosuppression and hepatic enzyme induction. Drugs able to interfere with the immune response, usually increased the level of inhibition of immune responses when given at the same time as TCDD. Treatment with 3-Methylcholanthrene before or after TCDD always resulted in additive immunosuppressive effect. Similar results were observed in enzymatic studies. In TCDD-TCDF combination when TCDD was given 2 day before and after TCDF, the effect observed in animals treated with both toxins usually was not statistically different from the effects (inhibition of immune parameters or enzymatic induction) caused by the most active compound used in that condition. Time-course experiments were consistent with the conclusion that inducers usually did not modify TCDD toxicity. If inducers had toxic effects by themselves, the effect of combined treatments was the sum of the effect of each drug.