Martinez-Larrañaga M R, Anadón A, Diaz M J, Fernandez R, Sevil B, Fernandez-Cruz M L, Fernandez M C, Martinez M A, Anton R
Department of Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Spain.
Toxicol Appl Pharmacol. 1996 Nov;141(1):185-94. doi: 10.1006/taap.1996.0275.
The effects of repeated exposure to fumonisin B1 (FB1) on hepatic and renal mixed function oxidase activities and peroxisomal proliferation has been examined in rats following intraperitoneal administration at three dose levels (0.125, 0.25, and 2.5 mg/kg) once a day for 6 days. At the two highest doses, FB1 increased the renal and hepatic N-demethylation of erythromycin (CYP3A1) and the hepatic O-deethylation of ethoxyresorufin (CYP1A1). FB1, at the highest dose of 2.5 mg/kg, also increased the renal O-deethylation of ethoxyresorufin. The liver, but not the kidney, was also susceptible to FB1-dependent induction of the 12- and 11-hydroxylation of lauric acid, suggesting induction of the CYP4A subfamily. Immunoblot studies employing solubilized microsomes from FB1-treated rats revealed that FB1, at the two highest doses, increased the apoprotein levels of CYP1A1 and CYP4A1. The same treatment with FB1 increased the beta-oxidation of palmitoyl-coenzyme A (CoA) in liver homogenates, and immunoblot analysis showed an increase in the apoprotein levels of the trans-2-enoyl-CoA hydratase trifunctional protein. The possible implications of these findings to the hepatocarcinogenicity of this mycotoxin are discussed.
在大鼠腹腔注射伏马菌素B1（FB1）三个剂量水平（0.125、0.25和2.5mg/kg），每天一次，共6天之后，研究了重复暴露于FB1对肝脏和肾脏混合功能氧化酶活性及过氧化物酶体增殖的影响。在两个最高剂量下，FB1增加了红霉素的肾脏和肝脏N-去甲基化（CYP3A1）以及乙氧基试卤灵的肝脏O-去乙基化（CYP1A1）。在最高剂量2.5mg/kg时，FB1还增加了乙氧基试卤灵的肾脏O-去乙基化。肝脏而非肾脏也易受FB1依赖的月桂酸12-和11-羟基化诱导，提示CYP4A亚家族被诱导。使用来自FB1处理大鼠的可溶微粒体进行的免疫印迹研究表明，在两个最高剂量下，FB1增加了CYP1A1和CYP4A1的载脂蛋白水平。用FB1进行相同处理增加了肝脏匀浆中棕榈酰辅酶A（CoA）的β-氧化，免疫印迹分析显示反式-2-烯酰辅酶A水合酶三功能蛋白的载脂蛋白水平增加。讨论了这些发现对这种霉菌毒素致癌性的可能影响。
