Bhandari Neetesh, Enongene E N, Riley Ronald T, Meredith Filmore I, Sharma Raghubir P
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2002 Feb;131(2):113-22. doi: 10.1016/s1532-0456(01)00280-0.
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.
伏马菌素B1（FB1）是轮枝镰孢菌的一种有毒代谢产物，是一种致癌物及多种动物疾病的病原体。我们之前的研究表明，肿瘤坏死因子-α（TNFα）参与了FB1诱导的毒性反应。为了进一步研究TNFα产生和信号传导的时间进程，将小鼠（每组4只）分为两组，分别皮下注射（s.c.）或口服（p.o.）溶剂或25 mg/kg的FB1单剂量，并在治疗后0、2、4、8、12和24小时处死。两种途径暴露于FB1后，肝脏和肾脏中的TNFα表达均增加，而脾脏无任何变化。口服FB1治疗比皮下注射途径导致更大的肝毒性，这表现为仅在口服FB1治疗后血浆中丙氨酸转氨酶和天冬氨酸转氨酶水平升高。口服治疗后8小时酶的增加与口服治疗后8小时观察到的最高TNFα表达相关，从而进一步证实了TNFα参与FB1毒性。口服FB1治疗后4小时，肝脏中的干扰素（IFN）-γ表达增加，提示TNFα和IFNγ在其诱导和肝毒性中可能具有联合作用。
