Temporal expression of fumonisin B1-induced tumor necrosis factor-α and interferon γ in mice

Fumonisin B-1 (FB1), a toxic metabolite of Fusarium verticillio ides, is a carcinogen and causative agent of various animal diseases. Our previous studies indicated the involvement of tumor necrosis factor-alpha (TNFalpha) in FB1-induced toxic responses. To further investigate the time-course of TNFalpha production and signaling mice (four/group) were treated subcutaneously (s.c.) or per os. (p.o.) with either vehicle or 25 mg/kg of FB1 as a single dose and sacrificed at 0, 2, 4, 8, 12 and 24 h after treatment. The TNFalpha expression was increased in liver and kidney after both routes of FB1 exposure without any alterations in spleen. The p.o.-route FB1 treatment caused greater hepatotoxicity compared to the s.c. route, as depicted by increased alanine aminotransferase and aspartate aminotransferase level in plasma, observed only after p.o. FB1 treatment. The increase in enzymes at 8 h after p.o. treatment correlated with the highest TNFalpha expression, also noted at 8 h after p.o. treatment, thus further confirming the involvement of TNFalpha in FB1 toxicity. The interferon (IFN)-gamma expression was increased in liver at 4 h after p.o. FB1 treatment, suggesting a possible combined role of TNFalpha and IFNgamma in their induction and hepatotoxicity. (C) 2002 Elsevier Science Inc. All rights reserved.