Mathur S, Constable P D, Eppley R M, Waggoner A L, Tumbleson M E, Haschek W M
Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61802, USA.
Toxicol Sci. 2001 Apr;60(2):385-96. doi: 10.1093/toxsci/60.2.385.
Fumonisins are a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Experimental administration of fumonisin induces hepatotoxicity in all species, including cattle, as well as nephrotoxicity in rats, rabbits, and sheep. We investigated the hepatotoxicity and nephrotoxicity of fumonisin B(1) to calves. Ten milk-fed male Holstein calves aged 7 to 14 days were instrumented to obtain blood and urine. Treated calves (n = 5) were administered fumonisin B(1) at 1 mg/kg, iv, daily and controls (n = 5) 10 ml 0.9% NaCl, iv, daily until euthanized on day 7. Fumonisin B(1)-treated calves were lethargic and had decreased appetite from day 4 onward, serum biochemical evidence of severe liver and bile duct injury, and impaired hepatic function. Treated calves also had biochemical evidence of renal injury that functionally involved the proximal convoluted tubules. Sphinganine and sphingosine concentrations in liver, kidney, lung, heart, and skeletal muscle were increased in treated calves. Sphinganine, but not sphingosine, concentration was increased in brains of treated calves. In fumonisin B(1)-treated calves, hepatic lesions were characterized by disorganized hepatic cords, varying severity of hepatocyte apoptosis, hepatocyte proliferation, and proliferation of bile ductular cells. Renal lesions in treated calves consisted of vacuolar change, apoptosis, karyomegaly, and proliferation of proximal renal tubular cells, as well as dilation of proximal renal tubules, which contained cellular debris and protein. This is the first report of fumonisin B(1)-induced renal injury and organ sphingolipid alterations in cattle.
伏马菌素是一类霉菌毒素，可改变鞘脂生物合成，并在马中诱发白质软化症，在猪中诱发肺水肿。实验性给予伏马菌素会在所有物种（包括牛）中诱发肝毒性，以及在大鼠、兔子和绵羊中诱发肾毒性。我们研究了伏马菌素B1对犊牛的肝毒性和肾毒性。选用10头7至14日龄以牛奶喂养的雄性荷斯坦犊牛，对其进行插管以获取血液和尿液。将处理组犊牛（n = 5）每天静脉注射1 mg/kg伏马菌素B1，对照组（n = 5）每天静脉注射10 ml 0.9%氯化钠，直至在第7天实施安乐死。从第4天起，接受伏马菌素B1处理的犊牛变得嗜睡，食欲下降，有严重肝脏和胆管损伤的血清生化证据，以及肝功能受损。处理组犊牛也有肾脏损伤的生化证据，且在功能上累及近端曲管。处理组犊牛的肝脏、肾脏、肺、心脏和骨骼肌中的鞘氨醇和鞘氨醇浓度升高。处理组犊牛大脑中的鞘氨醇浓度升高，但鞘氨醇浓度未升高。在接受伏马菌素B1处理的犊牛中，肝脏病变的特征是肝索紊乱、肝细胞凋亡程度不同、肝细胞增殖以及胆管细胞增殖。处理组犊牛的肾脏病变包括空泡变性、凋亡、核肿大和近端肾小管细胞增殖，以及近端肾小管扩张，其中含有细胞碎片和蛋白质。这是关于伏马菌素B1诱导牛肾损伤和器官鞘脂改变的首次报道。
