Temporal expression of fumonisin B(1)-induced tumor necrosis factor-alpha and interferon gamma in mice.
Fumonisin B(1) (FB(1)), a toxic metabolite of Fusarium verticillioides, is a carcinogen and causative agent of various animal diseases. Our previous studies indicated the involvement of tumor necrosis factor-alpha (TNF alpha) in FB(1)-induced toxic responses. To further investigate the time-course of TNF alpha production and signaling, mice (four/group) were treated subcutaneously (s.c.) or per os (p.o.) with either vehicle or 25 mg/kg of FB(1) as a single dose and sacrificed at 0, 2, 4, 8, 12 and 24 h after treatment. The TNF alpha expression was increased in liver and kidney after both routes of FB(1) exposure without any alterations in spleen. The p.o.-route FB(1) 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. FB(1) treatment. The increase in enzymes at 8 h after p.o. treatment correlated with the highest TNF alpha expression, also noted at 8 h after p.o. treatment, thus further confirming the involvement of TNF alpha in FB(1) toxicity. The interferon (IFN)-gamma expression was increased in liver at 4 h after p.o. FB(1) treatment, suggesting a possible combined role of TNF alpha and IFN gamma in their induction and hepatotoxicity.
Bhandari
Neetesh
N
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389, USA.
Enongene
E N
EN
Riley
Ronald T
RT
Meredith
Filmore I
FI
Sharma
Raghubir P
RP
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004906:Erythrocyte Count; D037341:Fumonisins; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009183:Mycotoxins / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D002264:Carboxylic Acids; D037341:Fumonisins; D009183:Mycotoxins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C056933:fumonisin B1; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase