The role of tumor necrosis factor alpha and the peroxisome proliferator-activated receptor alpha in modulating the effects of fumonisin in mouse liver.
Fumonisins are mycotoxins that are produced by Fusarium verticillioides found in corn and corn-based foods, and are suspected human esophageal carcinogens. Exposure of rodents to fumonisin B1 causes hepatotoxicity and results in alterations in the balance between cell proliferation and apoptosis in the liver. As the cytokine tumor necrosis factor alpha (TNFalpha) and the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) also modulate hepatocyte proliferation and apoptosis, we tested the hypothesis that fumonisin-induced hepatotoxicity in the liver is modulated by these factors. We examined the effects of dietary exposure to a fumonisin-containing culture material (CM) of the fungus F. verticillioides for 8 days or 5 weeks in the livers of mice lacking either TNFalpha or PPARalpha. Compared to wild-type mice TNFalpha-null mice exhibited increased hepatocyte proliferation and apoptosis. In contrast, PPARalpha-null and wild-type mice were found to exhibit similar patterns of hepatocyte apoptosis and proliferation when fed the CM diet. Overall, these findings provide evidence that TNFalpha, but not PPARalpha, plays a role in modulating fumonisin-induced hepatotoxicity in mice.
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Kenneth A
KA
Voss
Ronald
R
Riley
Corrie
C
Dunn
J
J
Christopher Corton
D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet; D005260:Female; D037341:Fumonisins / Q000633:toxicity*; D005670:Fusarium; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008938:Mitosis / Q000187:drug effects; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D037341:Fumonisins; D047493:PPAR alpha; D014409:Tumor Necrosis Factor-alpha; C056933:fumonisin B1; D042962:Acyl-CoA Oxidase; D013110:Sphingosine; C005682:safingol