Fumonisin B-1 is hepatotoxic and nephrotoxic in milk-fed calves

Fumonisins are a group of mycotoxins that alter sphingolipid biosynthesis a nd induce leukoencephalomalacia in horses and pulmonary edema in pigs. Expe rimental administration of fumonisin induces hepatotoxicity in all species, including cattle, as well as nephrotoxicity in rats, rabbits, and sheep. W e investigated the hepatotoxicity and nephrotoxicity of fumonisin B-1 to ca lves. Ten milk-fed male Holstein calves aged 7 to 14 days were instrumented to obtain blood and urine. Treated calves (n = 5) were administered fumoni sin B-1 at 1 mg/kg, iv, daily and controls (n = 5) 10 ml 0.9% NaCl, iv, dai ly until euthanized on day 7. Fumonisin B-1-treated calves were lethargic a nd had decreased appetite from day 4 onward, serum biochemical evidence of severe liver and bile duct injury, and impaired hepatic function. Treated c alves also had biochemical evidence of renal injury that functionally invol ved the proximal convoluted tubules. Sphinganine and sphingosine concentrat ions in liver, kidney, lung, heart, and skeletal muscle were increased in t reated calves. Sphinganine, but not sphingosine, concentration was increase d in brains of treated calves. Zn fumonisin B-1-treated calves, hepatic les ions were characterized by disorganized hepatic cords, varying severity of hepatocyte apoptosis, hepatocyte proliferation, and proliferation of bile d uctular 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 d ebris and protein. This is the first report of fumonisin B-1-induced renal injury and organ sphingolipid alterations in cattle.