Decreased fumonisin hepatotoxicity in mice with a targeted deletion of tumor necrosis factor receptor 1

摘要: Abstract Fumonisin B 1 (FB ), a mycotoxin produced by Fusarium verticillioides and related fungi infests corn other cereals, causes variety of toxic effects in different mammalian species. Hepatotoxicity is common response most The cellular responses FB involve inhibition ceramide synthase leading to accumulation free sphingoid bases corresponding induction tumor necrosis factor α (TNFα). We recently reported that hepatotoxicity was considerably reduced mouse strain lacking receptor 2 (TNFR2 or TNFR1b). To further investigate the relative contribution two TNFα receptors (TNFR1 TNFR2 P55 P75 receptors) we evaluated male C57BL/6J mice (WT) TNFR1 knockout (TNFRKO) strain, genetically modified targeted deletion this receptor. hepatotoxic five daily injections 2.25 mg/kg per day were observed WT but TNFRKO, evidenced microscopic evaluation liver increased concentrations circulating alanine aminotransferase aspartate aminotransferase. induced expression TNFα, similar increases sphinganine sphingosine livers both TNFRKO mice. Results indicated are required for -induced plays an important role such liver.