Fumonisin B1 is hepatotoxic and nephrotoxic in milk-fed calves

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

Research output: Contribution to journalArticlepeer-review

Abstract

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 dis-organized 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.

Original languageEnglish (US)
Pages (from-to)385-396
Number of pages12
JournalToxicological Sciences
Volume60
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Chelesterol
  • Fumonisin
  • Hepatotoxicity
  • Nephrotoxicity
  • Proximal renal tubules
  • Sphinganine
  • Sphingolipid
  • Sphingosine

ASJC Scopus subject areas

  • Toxicology

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