DIETARY FUMONISIN B-1 INDUCES DISRUPTION OF SPHINGOLIPID METABOLISM IN SPRAGUE-DAWLEY RATS - A NEW MECHANISM OF NEPHROTOXICITY
DIETARY FUMONISIN B-1 INDUCES DISRUPTION OF SPHINGOLIPID METABOLISM IN SPRAGUE-DAWLEY RATS - A NEW MECHANISM OF NEPHROTOXICITY
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DOI：
10.1093/jn/124.4.594
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发表时间：
1994-04-01
影响因子：
4.2
通讯作者：
VOSS, KA
中科院分区：
文献类型：
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作者：
RILEY, RT;HINTON, DM;VOSS, KA
伏马菌素是由几种镰刀菌产生的鞘脂生物合成的有效抑制剂。食用感染F.串珠状或高水平伏马菌素与几种动物疾病有关。在为期4周的喂养研究中，引起Sprague-Dawley大鼠肾毒性的伏马菌素B-1浓度远低于引起肝毒性所需的浓度。这项回顾性研究表明，超微结构病变的范围和严重程度与鞘脂代谢的破坏程度之间存在密切的相关性。与肝脏相比，肾脏对伏马菌素B-1诱导的鞘脂代谢破坏更敏感，在喂食15、50和150 μ g/g伏马菌素B-1的大鼠中，游离鞘氨醇、游离鞘氨醇以及游离鞘氨醇：游离鞘氨醇比率显着升高。尿中游离二氢鞘氨醇的积累和游离二氢鞘氨醇：游离鞘氨醇比值的升高密切反映了肾脏发生的变化。累积的二氢鞘氨醇和游离二氢鞘氨醇：游离鞘氨醇比率的升高与尿液中细胞的累积相关。因此，尿液而不是血清是检测伏马菌素诱导的肾损伤导致的游离鞘氨醇碱升高的首选液体。
Fumonisins are potent inhibitors of sphingolipid biosynthesis produced by several Fusarium species. Consumption of corn or corn products infected with F. moniliforme, or high levels of fumonisins, is associated with several animal diseases. In a 4-wk feeding study, the concentration of fumonisin B-1 that caused nephrotoxicity in Sprague-Dawley rats was much less than that required to cause hepatotoxicity. This retrospective study shows a close correlation between the extent and severity of ultrastructural lesions and the degree of disruption of sphingolipid metabolism. The kidney was more sensitive to fumonisin B-1-induced disruption of sphingolipid metabolism than liver with significant elevation of free sphingosine, free sphinganine, and the free sphinganine:free sphingosine ratio in rats fed 15, 50 and 150 mu g/g fumonisin B-1. Accumulation of free sphinganine and elevation of the free sphinganine: free sphingosine ratio in urine closely reflected the changes that occurred in kidney. The accumulated sphinganine and elevation of the free sphinganine:free sphingosine ratio was associated with accumulation of cells in urine. Thus, urine rather than serum is the fluid of choice for detecting elevated free sphingoid bases generated as a consequence of fumonisin-induced kidney damage.