Role of metabolic activation by cytochrome P450 in thioacetamide-induced suppression of antibody response in male BALB/c mice

Effects of thioacetamide on antibody response to sheep red blood cells were investigated in male BALB/c mice. When mice were treated intraperitoneally with thioacetamide once, the antibody response was significantly suppresse d at 200 mg/kg with hepatotoxicity. When mice were treated intraperitoneall y with thioacetamide for 7 consecutive days, the antibody response was supp ressed at 50 mg/kg without hepatotoxicity. To determine the possible role o f metabolic activation by cytochrome P450 in thioacetamide-induced suppress ion of antibody response, mice were pretreated with phenobarbital intraperi toneally for 3 days, followed by intraperitoneal administration of 100 mg/k g of thioacetamide for 3 days. The elevated activities of serum aspartate a minotransferase and alanine aminotransferase by thioacetamide were potentia ted by phenobarbital pretreatment. The suppression of antibody response by thioacetamide was potentiated by phenobarbital. In liver microsomes, the ac tivities of P450 2B-specific enzymes were induced by phenobarbital. Our pre sent results suggest that thioacetamide may require metabolic activation by P450 to its immunosuppressive form(s). (C) 2000 Elsevier Science ireland L td. All rights reserved.