Sharma R P, Dugyala R R, Voss K A
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens 30602, USA.
J Comp Pathol. 1997 Nov;117(4):371-81. doi: 10.1016/s0021-9975(97)80084-9.
Fumonisin B1, a mycotoxin produced by Fusarium moniliforme, inhibits the activity of ceramide synthetase, the key enzyme in sphingolipid biosynthesis, leading to accumulation ofsphinganine and sphingosine. Ceramide and other sphingolipid pathways have been implicated in signal-induced apoptosis in cells. Groups of male BALB/c mice received subcutaneous injections (0, 0.25, 0.75, 2.25 or 6.25 mg/kg) of fumonisin B1 daily for 5 days and the liver and kidneys were sampled 1 day after the last injection. A decrease in kidney weight was observed after fumonisin treatment. A "blind" random evaluation of stained sections revealed dose-dependent fumonisin B1-associated hepatic and renal lesions in all groups. Terminal uridine triphosphate (UTP) nick-end labelling (TUNEL) in liver and kidney sections confirmed the presence of dose-related apoptotic cells at all treatment levels. Thus fumonisin B1 produced apoptosis after a brief exposure to relatively low doses. The toxicity of fumonisin B1 was greater than that previously found in studies on oral toxicity.
伏马菌素B1是由串珠镰刀菌产生的一种霉菌毒素，它抑制神经酰胺合成酶的活性，而神经酰胺合成酶是鞘脂生物合成中的关键酶，导致鞘氨醇和鞘氨醇的积累。神经酰胺和其他鞘脂途径与细胞中信号诱导的凋亡有关。将雄性BALB/c小鼠分组，每天皮下注射（0、0.25、0.75、2.25或6.25毫克/千克）伏马菌素B1，持续5天，并在最后一次注射后1天采集肝脏和肾脏样本。伏马菌素处理后观察到肾脏重量下降。对染色切片进行“盲法”随机评估发现，所有组均存在剂量依赖性的与伏马菌素B1相关的肝脏和肾脏病变。肝脏和肾脏切片中的末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）证实，在所有处理水平下均存在剂量相关的凋亡细胞。因此，伏马菌素B1在短期接触相对低剂量后即可产生凋亡。伏马菌素B1的毒性大于先前口服毒性研究中发现的毒性。
