Voss K A, Plattner R D, Riley R T, Meredith F I, Norred W P
Toxicology and Mycotoxin Research Unit, USDA, Richard B. Russell Agricultural Research Center, Athens, Georgia 30604-5677, USA.
Mycopathologia. 1998;141(1):45-58. doi: 10.1023/a:1006810916344.
Fumonisins are mycotoxins produced by Fusarium moniliforme, F. proliferatum, and related Fusarium species found on corn. They occur naturally in corn-based feeds and foods and are suspected human esophageal carcinogens. Fumonisin B1 (FB1), the most common homologue, causes the animal diseases associated with F. moniliforme. Hepato- and nephrotoxicities, disrupted sphingolipid metabolism, and liver cancer have been found in rats fed FB1. To determine the in vivo effects of diets containing fumonisins B2 (FB2) or B3 or (FB3), male rats were fed culture materials (CM) of FB1 non-producing F. moniliforme isolates to provide low (4.6-6.7 ppm), mid (32-49 ppm) or high (219-295 ppm) dietary levels of either FB2 (FB2CM) or FB3 (FB3CM). Other groups were fed culture material of an FB1 producing isolate (FB1CM) providing 6.9, 53 or 303 ppm total fumonisins (FB1: FB2: FB3 = 1.0: 0.38: 0.15) and a tenth group was fed a control diet having no detectable fumonisins. One-half (n = 5/group) the animals were killed after three weeks, at which time the toxicological and histopathological effects of the three culture materials were similar, mimicked the effects of FB1, and included decreased body weight gains, serum chemical indicators of hepatotoxicity, decreased kidney weights, and apoptosis of hepatocytes and kidney tubular epithelium. FB1CM, FB2CM, and FB3CM affected sphingolipids, causing increased sphinganine to sphingosine ratios (Sa/So) in both liver and kidneys. The remaining animals (n = 5/group0 were fed a control diet for three additional weeks. All body weight and tissue specific effects, including increased Sa/So, induced by the FB2Cm, FB3CM and low level FB1CM diets were absent following the recovery period. Except for mild biliary lesions found in the high dose of FB1CM group and a few apoptotic hepatocytes present in one mid- and two high-dose FB1CM rats, no evidence of toxicity remained in these groups, following the recovery period.
伏马菌素是由串珠镰刀菌、层出镰刀菌以及在玉米上发现的相关镰刀菌属物种产生的霉菌毒素。它们天然存在于以玉米为基础的饲料和食品中,并且被怀疑是人类食管癌的致癌物。伏马菌素B1(FB1)是最常见的同系物,可引发与串珠镰刀菌相关的动物疾病。在喂食FB1的大鼠中发现了肝毒性和肾毒性、鞘脂代谢紊乱以及肝癌。为了确定含有伏马菌素B2(FB2)或B3(FB3)的日粮的体内效应,给雄性大鼠喂食不产生FB1的串珠镰刀菌分离株的培养物(CM),以提供低(4.6 - 6.7 ppm)、中(32 - 49 ppm)或高(219 - 295 ppm)日粮水平的FB2(FB2CM)或FB3(FB3CM)。其他组喂食产生FB1的分离株的培养物(FB1CM),其提供6.9、53或303 ppm的总伏马菌素(FB1∶FB2∶FB3 = 1.0∶0.38∶0.15),第十组喂食无可检测伏马菌素的对照日粮。三周后处死一半动物(每组n = 5),此时三种培养物的毒理学和组织病理学效应相似,模拟了FB1的效应,包括体重增加减少、肝毒性的血清化学指标、肾脏重量减轻以及肝细胞和肾小管上皮细胞凋亡。FB1CM、FB2CM和FB3CM影响鞘脂,导致肝脏和肾脏中的鞘氨醇与鞘脂醇比率(Sa/So)增加。其余动物(每组n = 5)再喂食三周对照日粮。在恢复期后,由FB2CM、FB3CM和低水平FB1CM日粮诱导的所有体重和组织特异性效应,包括Sa/So增加,均消失。在恢复期后,除了高剂量FB1CM组中发现的轻度胆管病变以及一只中剂量和两只高剂量FB1CM大鼠中存在的一些凋亡肝细胞外,这些组中没有毒性证据留存。