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膳食伏马菌素B1诱导Sprague-Dawley大鼠鞘脂代谢紊乱:一种肾毒性的新机制。

Dietary fumonisin B1 induces disruption of sphingolipid metabolism in Sprague-Dawley rats: a new mechanism of nephrotoxicity.

作者信息

Riley R T, Hinton D M, Chamberlain W J, Bacon C W, Wang E, Merrill A H, Voss K A

机构信息

Toxicology and Mycotoxins Research Unit, USDA-ARS, Athens, GA 30613.

出版信息

J Nutr. 1994 Apr;124(4):594-603. doi: 10.1093/jn/124.4.594.

DOI:10.1093/jn/124.4.594
PMID:8145083
Abstract

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 B1 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 B1-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 micrograms/g fumonisin B1. 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.

摘要

伏马菌素是由几种镰刀菌属产生的鞘脂生物合成的强效抑制剂。食用被串珠镰刀菌感染的玉米或玉米制品,或高含量的伏马菌素,与多种动物疾病有关。在一项为期4周的喂养研究中,导致斯普拉格-道利大鼠肾毒性的伏马菌素B1浓度远低于导致肝毒性所需的浓度。这项回顾性研究表明,超微结构损伤的程度和严重程度与鞘脂代谢紊乱程度密切相关。肾脏对伏马菌素B1诱导的鞘脂代谢紊乱比肝脏更敏感,在喂食15、50和150微克/克伏马菌素B1的大鼠中,游离鞘氨醇、游离鞘氨醇胺和游离鞘氨醇胺:游离鞘氨醇比值显著升高。尿液中游离鞘氨醇胺的积累和游离鞘氨醇胺:游离鞘氨醇比值的升高密切反映了肾脏中发生的变化。积累的鞘氨醇胺和游离鞘氨醇胺:游离鞘氨醇比值的升高与尿液中细胞的积累有关。因此,尿液而非血清是检测伏马菌素诱导的肾损伤导致的游离鞘脂碱升高的首选液体。

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