Journal Article

Fumonisin B<sub>1</sub> Is Hepatotoxic and Nephrotoxic in Milk-Fed Calves

Sheerin Mathur, Peter D. Constable, Robert M. Eppley, Amy L. Waggoner, Mike E. Tumbleson and Wanda M. Haschek

in Toxicological Sciences

Volume 60, issue 2, pages 385-396
Published in print April 2001 | ISSN: 1096-6080
Published online April 2001 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/60.2.385
Fumonisin B1 Is Hepatotoxic and Nephrotoxic in Milk-Fed Calves

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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 B1 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 B1 at 1 mg/kg, iv, daily and controls (n = 5) 10 ml 0.9% NaCl, iv, daily until euthanized on day 7. Fumonisin B1-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 B1-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 B1-induced renal injury and organ sphingolipid alterations in cattle.

Keywords: fumonisin; sphingosine; sphinganine; sphingolipid; hepatotoxicity; cholesterol; nephrotoxicity; proximal renal tubules

Journal Article.  7447 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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