Clinical and clinicopathologic features of dogs that consumed foodborne hepatotoxic aflatoxins: 72 cases (2005–2006)

Diane M. Dereszynski Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Diane M. Dereszynski in
Current site
Google Scholar
PubMed
Close
 DVM
,
Sharon A. Center Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Sharon A. Center in
Current site
Google Scholar
PubMed
Close
 DVM, DACVIM
,
John F. Randolph Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by John F. Randolph in
Current site
Google Scholar
PubMed
Close
 DVM, DACVIM
,
Marjory B. Brooks Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Marjory B. Brooks in
Current site
Google Scholar
PubMed
Close
 DVM, DACVIM
,
Alice G. Hadden Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Alice G. Hadden in
Current site
Google Scholar
PubMed
Close
 DVM
,
Kiran S. Palyada Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Kiran S. Palyada in
Current site
Google Scholar
PubMed
Close
 BVSc, MVSc, PhD
,
Sean P. McDonough Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Sean P. McDonough in
Current site
Google Scholar
PubMed
Close
 DVM, DACVP, PhD
,
Joanne Messick Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Joanne Messick in
Current site
Google Scholar
PubMed
Close
 DVM, DACVP, PhD
,
Tracy Stokol Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Tracy Stokol in
Current site
Google Scholar
PubMed
Close
 BVSc, DACVP, PhD
,
Karyn L. Bischoff Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Karyn L. Bischoff in
Current site
Google Scholar
PubMed
Close
 DVM, MS, DABVT
,
Stuart Gluckman Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Stuart Gluckman in
Current site
Google Scholar
PubMed
Close
 DVM
, and
Sara Y. Sanders Departments of Clinical Sciences, Population Medicine and Diagnostic Sciences, and Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853; and Mendon Village Animal Hospital, 1380B Pittsford-Mendon Rd, Mendon, NY 14506.

Search for other papers by Sara Y. Sanders in
Current site
Google Scholar
PubMed
Close
 DVM

Abstract

Objective—To characterize clinical signs, clinicopathologic features, treatments, and survival in dogs with naturally acquired foodborne aflatoxicosis.

Design—Retrospective case series.

Animals—72 dogs that consumed aflatoxin-contaminated commercial dog food.

Procedures—Medical records of affected dogs were reviewed. Between December 2005 and March 2006, dogs were identified as having foodborne aflatoxin hepatotoxicosis on the basis of the history of consumption of contaminated food or characteristic histopathologic lesions (subject dog or a recently deceased dog in the same household or kennel). Recorded information included signalment, clinical features, clinicopathologic test results, treatments, and survival. Data were analyzed by survival status.

Results—Most dogs were of large breeds from breeding kennels. No significant differences were found in age or weight between 26 (36%) survivor dogs and 46 (64%) nonsurvivor dogs. Severity of clinical signs varied widely; 7 dogs died abruptly. In order of onset, clinical features included anorexia, lethargy, vomiting, jaundice, diarrhea (melena, hematochezia), abdominal effusion, peripheral edema, and terminal encephalopathy and hemorrhagic diathesis. Common clinicopathologic features included coagulopathic and electrolyte disturbances, hypoproteinemia, increased serum liver enzyme activities, hyperbilirubinemia, and hypocholesterolemia. Cytologic hepatocellular lipid vacuolation was confirmed in 11 dogs examined. In comparisons of clinicopathologic test results between survivor and nonsurvivor dogs, only granular cylindruria (7/21 dogs) consistently predicted death. Best early markers of aflatoxicosis were low plasma activities of anticoagulant proteins (protein C, antithrombin) and hypocholesterolemia. Despite aggressive treatment, many but not all severely affected dogs died.

Conclusions and Clinical Relevance—Serum liver enzyme activities and bilirubin concentration were unreliable early markers of aflatoxin hepatotoxicosis in dogs. Hypocholesterolemia and decreased plasma protein C and antithrombin activities may function as exposure biomarkers.

Abstract

Objective—To characterize clinical signs, clinicopathologic features, treatments, and survival in dogs with naturally acquired foodborne aflatoxicosis.

Design—Retrospective case series.

Animals—72 dogs that consumed aflatoxin-contaminated commercial dog food.

Procedures—Medical records of affected dogs were reviewed. Between December 2005 and March 2006, dogs were identified as having foodborne aflatoxin hepatotoxicosis on the basis of the history of consumption of contaminated food or characteristic histopathologic lesions (subject dog or a recently deceased dog in the same household or kennel). Recorded information included signalment, clinical features, clinicopathologic test results, treatments, and survival. Data were analyzed by survival status.

Results—Most dogs were of large breeds from breeding kennels. No significant differences were found in age or weight between 26 (36%) survivor dogs and 46 (64%) nonsurvivor dogs. Severity of clinical signs varied widely; 7 dogs died abruptly. In order of onset, clinical features included anorexia, lethargy, vomiting, jaundice, diarrhea (melena, hematochezia), abdominal effusion, peripheral edema, and terminal encephalopathy and hemorrhagic diathesis. Common clinicopathologic features included coagulopathic and electrolyte disturbances, hypoproteinemia, increased serum liver enzyme activities, hyperbilirubinemia, and hypocholesterolemia. Cytologic hepatocellular lipid vacuolation was confirmed in 11 dogs examined. In comparisons of clinicopathologic test results between survivor and nonsurvivor dogs, only granular cylindruria (7/21 dogs) consistently predicted death. Best early markers of aflatoxicosis were low plasma activities of anticoagulant proteins (protein C, antithrombin) and hypocholesterolemia. Despite aggressive treatment, many but not all severely affected dogs died.

Conclusions and Clinical Relevance—Serum liver enzyme activities and bilirubin concentration were unreliable early markers of aflatoxin hepatotoxicosis in dogs. Hypocholesterolemia and decreased plasma protein C and antithrombin activities may function as exposure biomarkers.

Contributor Notes

Dr. Dereszynski's present address is VCA West Los Angeles Animal Hospital, 1818 S Sepulveda Blvd, Los Angeles, CA 90025.

Dr. Hadden's present address is VCA Roberts Animal Hospital, 516 Washington St, Hanover, MA 02339.

Dr. Messick's present address is Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

Presented in part at the 24th Annual Forum of the American College of Veterinary Internal Medicine, Louisville, June 2006.

The authors thank Dr. Hollis N. Erb for statistical assistance.

Address correspondence to Dr. Center.
  • 1.

    Eaton DL, Gallagher EP. Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol 1994;34:135172.

  • 2.

    Wang JS, Groopman JD. DNA damage by mycotoxins. Mutat Res 1999;424:167181.

  • 3.

    Zimmerman HJ. Hepatotoxicity. The adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 1999;255294.

    • Search Google Scholar
    • Export Citation
  • 4.

    Bennett JW, Klich M. Mycotoxins. Clin Microbiol Rev 2003;16:497516.

  • 5.

    McLean M, Dutton MF. Cellular interactions and metabolism of aflatoxin: an update. Pharmacol Ther 1995;65:163192.

  • 6.

    Siebold HR, Bailey WS. An epizootic of hepatitis in the dog. J Am Vet Med Assoc 1952;121:201206.

  • 7.

    Siebold HR. Hepatitis X in dogs. Vet Med (Praha) 1953;48:242243.

  • 8.

    Newberne JW, Bailey WS, Seibold HR. Notes on a recent outbreak and experimental reproduction of hepatitis X in dogs. J Am Vet Med Assoc 1955;127:5962.

    • Search Google Scholar
    • Export Citation
  • 9.

    Bailey WS, Groth AH Jr. The relationship of hepatitis X of dogs and moldy corn poisoning of swine. J Am Vet Med Assoc 1959;134:514516.

    • Search Google Scholar
    • Export Citation
  • 10.

    Blout WP. Turkey “X” disease. Turkeys 1961;9:5558,61,77.

  • 11.

    Forgacs J. Mycotoxicoses—the neglected diseases. Feedstuffs 1962;34:124134.

  • 12.

    Wilson BJ, Teer PA, Barney GH, et al. Relationship of aflatoxin to epizootics of toxic hepatitis among animals in southern United States. Am J Vet Res 1967;28:12171230.

    • Search Google Scholar
    • Export Citation
  • 13.

    Chaffee VW, Edds GT, Himes JA, et al. Aflatoxicosis in dogs. Am J Vet Res 1969;30:17371749.

  • 14.

    Newberne PM. Chronic aflatoxicosis. J Am Vet Med Assoc 1973;163:12621267.

  • 15.

    Newberne PM, Russo R, Wogan GN. Acute toxicity of aflatoxin B1 in the dog. Pathol Vet 1966;3:331340.

  • 16.

    Greene CE, Barsanti JA, Jones BD. Disseminated intravascular coagulation complicating aflatoxicosis in dogs. Cornell Vet 1977;67:2949.

  • 17.

    Liggett AD, Colvin BM, Beaver RW, et al. Canine aflatoxicosis: a continuing problem. Vet Hum Toxicol 1986;28:428430.

  • 18.

    Bastianello SS, Nesbit JW, Williams MC, et al. Pathological findings in a natural outbreak of aflatoxicosis in dogs. Onderstepoort J Vet Res 1987;54:635640.

    • Search Google Scholar
    • Export Citation
  • 19.

    Hagiwara MK, Kogika MM, Malucelli BE. Disseminated intravascular coagulation in dogs with aflatoxicosis. J Small Anim Pract 1990;31:239243.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Guengerich FP. Cytochrome P450 oxidations in the generation of reactive electrophiles: epoxidation and related reactions. Arch Biochem Biophys 2003;409:5971.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Guengerich FP. Principles of covalent binding of reactive metabolites and examples of activation of bis-electrophiles by conjugation. Arch Biochem Biophys 2005;433:369378.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Denning DW. Aflatoxin and human disease. Adverse Drug React Acute Poisoning Rev 1987;6:175209.

  • 23.

    Singh J, Singh S, Dani HM, et al. Interactions of aflatoxin B1 with SRP components can disrupt protein targeting. Cell Biochem Funct 2005;23:913.

  • 24.

    Staib F, Hussain SP, Hofseth LJ, et al. TP53 and liver carcinogenesis. Hum Mutat 2003;21:201216.

  • 25.

    Raney KD, Meyer DJ, Ketterer B, et al. Glutathione conjugation of aflatoxin B1 exo- and endo-epoxides by rat and human glutathione s-transferases. Chem Res Toxicol 1992;5:470478.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Cardonna TD, Ilangantileke SG, Noomhorm A. Mycotoxin prevention and control in foodgrains. Section VI—mycotoxins in grain in selected countries. Aflatoxin research on grain in Asia—its problems and possible solutions. Available at: www.fao.org/docrep/X5036E/x5036E1e.htm. Accessed Jan 3, 2006.

    • Search Google Scholar
    • Export Citation
  • 27.

    Patterson DS, Allcroft R. Metabolism of aflatoxin in susceptible and resistant animal species. Food Cosmet Toxicol 1970;8:4353.

  • 28.

    Center SA, Warner KL, Erb HN. Liver glutathione concentrations in dogs and cats with naturally occurring liver disease. Am J Vet Res 2002;63:11871197.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Watanabe T, Sugiura T, Manabe S, et al. Low glutathione Stransferase dogs. Arch Toxicol 2004;78:218225.

  • 30.

    Tulayakul P, Sakuda S, Dong KS, et al. Comparative activities of glutathione-S-transferase and dialdehyde reductase toward aflatoxin B1 in livers of experimental and farm animals. Toxicon 2005;46:204209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Ketterer PJ, Williams ES, Blaney BJ, et al. Canine aflatoxicosis. Aust Vet J 1975;51:355357.

  • 32.

    Agag BI. Mycotoxins in foods and feeds: 1-aflatoxins. Assiut Univ Bull Environ Res 2004;7:173206.

  • 33.

    Newman SJ, Smith JR, Stenske KA, et al. Aflatoxicosis in nine dogs after exposure to contaminated commercial dog food. J Vet Diagn Invest 2007;19:168175.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957;17:237246.

  • 35.

    Stokol T, Brooks MB, Erb HN. Effect of citrate concentration on coagulation test results in dogs. J Am Vet Med Assoc 2000;217:16721677.

  • 36.

    Triplett DA, Harms CS. Factor assays. In: Triplett DA, ed. Procedures for the coagulation laboratory. Chicago: American Society of Clinical Pathologists Press, 1981;3857.

    • Search Google Scholar
    • Export Citation
  • 37.

    Williams JH, Phillips TD, Jolly PE, et al. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr 2004;80:11061122.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Center SA. Interpretation of liver enzymes. Vet Clin North Am Small Anim Pract 2007;37:297333.

  • 39.

    Pack R, Heck R, Dienes HP, et al. Isolation, biochemical characterization, long-term culture, and phenotype modulation of oval cells from carcinogen-fed rats. Exp Cell Res 1993;204:198209.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40.

    Solter P, Liu Z, Guzman R. Decreased hepatic ALT synthesis is an outcome of subchronic microcystin-LR toxicity. Toxicol Appl Pharmacol 2000;164:216220.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41.

    DeVries SE, Galey FD, Namikoshi M, et al. Clinical and pathologic findings of blue-green algae (Microcystis aeruginosa) intoxication in a dog. J Vet Diagn Invest 1993;5:403408.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Tedesco D, Steidler S, Galletti S, et al. Efficacy of silymarinphospholipid complex in reducing the toxicity of aflatoxin B1 in broiler chicks. Poult Sci 2004;83:18391843.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Kato R, Onoda K, Omori Y. The effect of aflatoxin B1 on incorporation of 14C-acetate into cholesterol by rat liver. Experientia 1969;25:1026.

  • 44.

    Ketterer B, Coles B, Meyer DJ. The role of glutathione in detoxication. Environ Health Perspect 1983;49:5969.

  • 45.

    Guengerich FP, Johnson WW, Shimada T, et al. Activation and deactivation of aflatoxin B1. Mutat Res 1998;402:121128.

  • 46.

    Dirr HW, Schabort JC. Aflatoxin B1 transport in rat blood plasma. Binding to albumin in vivo and in vitro and spectrofluorometric studies into the nature of the interaction. Biochim Biophys Acta 1986;881:383390.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Chang LW, Hsia SMT, Chan PC, et al. Macromolecular adducts: biomarkers for toxicity and carcinogenesis. Annu Rev Pharmacol Toxicol 1994;34:4167.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Turner PC, Dingley KH, Coxhead J, et al. Detectable levels of serum aflatoxin B1-albumin adducts in the United Kingdom population: implications for aflatoxin B1 exposure in the United Kingdom. Cancer Epidemiol Biomarkers Prev 1998;7:441447.

    • Search Google Scholar
    • Export Citation
  • 49.

    Ringot D, Chango A, Schneider Y-J, et al. Toxicokinetics and toxicodynamics of ochratoxin A, an update. Chem Biol Interact 2006;159:1846.

  • 50.

    Valdivia AG, Martinez A, Damian FJ, et al. Efficacy of N-acetylcysteine to reduce the effects of aflatoxin B1 intoxication in broiler chickens. Poult Sci 2001;80:727734.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51.

    Rastogi R, Srivastava AK, Rastogi AK. Long term effect of aflatoxin B1 on lipid peroxidation in rat liver and kidney: effect of picroliv and silymarin. Phytother Res 2001;15:307310.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52.

    Center SA. Metabolic, antioxidant, nutraceutical, probiotic, and herbal therapies relating to the management of hepatobiliary disorders. Vet Clin North Am Small Anim Pract 2004;34:67172.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 53.

    Asuzu IU, Shetty SN, Obidoa O. The interaction of aflatoxin B1 with vitamin K, phenylbutazone, and sulfamethoxine in rats. Biochem Med Metab Biol 1988;39:158167.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54.

    Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr 2004;80:143148.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 55.

    Center SA. Safe weight loss in cats. In: Reinhart GA, Carey DP, eds. Recent advances in canine and feline nutrition, Proceedings of the Iam's Nutrition Symposium. Vol 2.1998;165181.

    • Search Google Scholar
    • Export Citation
  • 56.

    Sachan DS, Yatim AM. Suppression of aflatoxin B1-induced lipid abnormalities and macromolecule-adduct formation by L-carnitine. J Environ Pathol Toxicol Oncol 1992;11:205210.

    • Search Google Scholar
    • Export Citation
  • 57.

    Yatim AM, Sachan DS. Carnitine alters binding of aflatoxin to DNA and proteins in rat hepatocytes and cell-free systems. J Nutr 2001;131:19031908.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 58.

    Citil M, Gunes V, Atakisi O, et al. Protective effect of L-carnitine against oxidative damage caused by experimental chronic aflatoxicosis in quail (Coturnix coturnix). Acta Vet Hung 2005;53:319324.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 59.

    Bammler TK, Slone DH, Eaton DL. Effects of dietary oltipraz and ethoxyquin on aflatoxin B1 biotransformation in non-human primates. Toxicol Sci 2000;54:3041.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 60.

    Clapper ML. Chemopreventive activity of oltipraz. Pharmacol Ther 1998;78:1727.

  • 61.

    Clark JD, Hatch RC, Jain AV, et al. Effect of enzyme inducers and inhibitors and glutathione precursor and depleter on induced acute aflatoxicosis in rabbits. Am J Vet Res 1982;43:10271033.

    • Search Google Scholar
    • Export Citation
  • 62.

    Clark JD, Jain AV, Hatch RC. Effects of various treatments on induced chronic aflatoxicosis in rabbits. Am J Vet Res 1982;43:106110.

Advertisement