Fumonisin B(1) is hepatotoxic and nephrotoxic in milk-fed calves.
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.
Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61802, USA.
S
S
Mathur
P D
PD
Constable
R M
RM
Eppley
A L
AL
Waggoner
M E
ME
Tumbleson
W M
WM
Haschek
D000818:Animals; D000833:Animals, Suckling / Q000097:blood; D000855:Anorexia / Q000139:chemically induced; D001652:Bile Ducts / Q000187:drug effects / Q000473:pathology; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000633:toxicity*; D002417:Cattle; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D037341:Fumonisins; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009206:Myocardium / Q000378:metabolism; D012894:Sleep Stages / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014018:Tissue Distribution
D002264:Carboxylic Acids; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1; D013110:Sphingosine; C005682:safingol