Veterinary Medicine - October 2007 - (Page 650)

Toxicology Brief PEER-REVIEWED of bacteremia and sepsis. Using antibiotics directed toward gram-negative bacteria is suggested. Metronidazole can be used in combination with amoxicillin, ampicillin, cephalexin, or cefadroxil. Metronidazole is effective against gram-negative anaerobes that produce ammonia, so it may help prevent hepatoencephalopathy as well as sepsis.43 Because metronidazole is metabolized by the liver and has been reported to cause hepatotoxicosis, reducing the dosage by 50% (to 5 mg/kg twice a day) may be appropriate in patients with aflatoxicosis.47 toxicosis.49 Thus, recovering dogs should be fed a balanced canine diet. Avoid protein-restricted diets unless hepatoencephalopathy is suspected. In cases of hepatoencephalopathy, parenteral nutrition may be preferred.43 ACKNOWLEDGMENTS The author wishes to thank Lisa Murphy, VMD, DABT, and Meredith Daly, VMD, for their contributions to this article. REFERENCES 1. Seibold HR, Bailey WS. An epizootic of hepatitis in the dog. J Am Vet Med Assoc 1952;121:201-206. 2. Seibold HR. Hepatitis X in dogs. Vet Med 1953;48:242-243. 3. 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;127:59-62. 4. Chaffee VW, Edds GT, Himes JA, et al. Aflatoxicosis in dogs. Am J Vet Res 1969;30:1737-1749. 5. Bailey WS, Groth AH. The relationship of hepatitis X of dogs and moldy corn poisoning of swine. J Am Vet Med Assoc 1959;134:514-516. 6. Newberne PM, Russo R, Wogan GN. Acute toxicity of aflatoxin B1 in the dog. Pathol Vet 1966;3:331-340. 7. Edds GT. Acute aflatoxicosis: a review. J Am Vet Med Assoc 1973;162:304-309. 8. Newberne PM. Chronic aflatoxicosis. J Am Vet Med Assoc 1973;163:1262-1267. 9. 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;80:1106-1122. 10. Kuilman ME, Maas RF, Fink-Gremmels JF. Cytochrome P450mediated metabolism and cytotoxicity of aflatoxin B(1) in bovine hepatocytes. Toxicol In Vitro 2000;14:321-327. 11. Wang JS, Groopman JD. DNA damage by mycotoxins. Mutat Res 1999;424:167-181. 12. Lee NA, Wang S, Allan RD, et al. A rapid aflatoxin B1 ELISA: development and validation with reduced matrix effects for peanuts, corn, pistachio, and Soybeans. J Agric Food Chem 2004;52:2746-2755. 13. Stenske KA, Smith JR, Newman SJ, et al. Aflatoxicosis in dogs and dealing with suspected contaminated commercial foods. J Am Vet Med Assoc 2006;228:1686-1691. 14. U.S. Food and Drug Administration. FDA issues consumer alert on contaminated pet food. Available at: http://www.fda .gov/bbs/topics/NEWS/2005/NEW01290.html. Accessed Jan 15, 2007. 15. Ketterer PJ, Williams ES, Blaney BJ, et al. Canine aflatoxicosis. Aust Vet J 1975;51:355-357. 16. Liggett AD, Colvin BM, Beaver RW, et al. Canine aflatoxicosis: a continuing problem. Vet Hum Toxicol 1986;28:428-430. 17. Bastianello SS, Nesbit JW, Williams MC, et al. Pathological findings in a natural outbreak of aflatoxicosis in dogs. Onderstepoort J Vet Res 1987;54:635-640. 18. Hagiwara MK, Kogika MM, Malucelli BE. Disseminated intravascular coagulation in dogs with aflatoxicosis. J Small Anim Pract 1990;31:239-243. 19. Bingham AK, Huebner HJ, Phillips TD, et al. Identification and reduction of urinary aflatoxin metabolites in dogs. Food Chem Toxicol 2004;42:1851-1858. 20. Gallagher EP, Kunze KL, Stapleton PL, et al. The kinetics of aflatoxin B1 oxidation by human cDNA-expressed and human liver microsomal cytochromes P450 1A2 and 3A4. Toxicol Appl Pharmacol 1996;141:595-606. 21. Neal GE, Eaton DL, Judah DJ, et al. Metabolism and toxicity of aflatoxins M1 and B1 in human-derived in vitro studies. Toxicol Appl Pharmacol 1998;151:152-158. 22. 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;5:470-478. MONITORING Frequently monitor the clinical signs; hepatic enzyme activities; electrolyte, cholesterol, and bilirubin concentrations; coagulation parameters; and hepatic function of patients with aflatoxicosis. Pay particular attention to any signs of DIC, hepatoencephalopathy, or severe bleeding. Recovering dogs should undergo periodic serum chemistry profiles and liver function testing (e.g. bile acid assay). Also screen dogs with a history of aflatoxin ingestion but no clinical signs for biochemical or hematologic abnormalities because clinical signs of aflatoxicosis are not always immediately apparent, and early treatment may decrease morbidity and mortality.13,16,18 Antiemetics and gastrointestinal protectants Patients with aflatoxicosis frequently present with a history of progressive vomiting. A constant-rate infusion of metoclopramide is a good choice for initially treating these animals. If the vomiting is refractory to treatment with metoclopramide, adding a serotonin antagonist such as dolasetron or ondansetron may provide relief. Also consider sucralfate, famotidine, and other gastrointestinal protectants in patients with aflatoxicosis to manage ulceration and decrease acid in the gastrointestinal tract.13,43 LONG-TERM PATIENT OUTCOME Dogs with aflatoxicosis can develop chronic liver disease and may be prone to developing neoplastic hepatic disorders. Hepatocarcinogenicity has been documented as a sequela to aflatoxin exposure in people, but no information is available regarding carcinogenicity in dogs.11 Control of hepatoencephalopathy In patients showing signs of hepatoencephalopathy, medications such as lactulose, neomycin sulfate, metronidazole, and flumazenil may be warranted. More information on treating hepatoencephalopathy in patients with acute liver failure is found elsewhere.43 SUMMARY Canine aflatoxicosis occurs from ingestion of aflatoxin-contaminated foods. Aflatoxins cause severe hepatic damage that frequently results in liver failure. The mainstays of treatment are hepatoprotective nutraceuticals, fluid therapy, blood component therapy, vitamin K1, antiemetics, and gastrointestinal protectants. While aflatoxicosis is fatal in most patients with overt signs of intoxication, some dogs may recover slowly with long-term care. O Nutrition A high-protein diet combined with aflatoxin exposure has been associated with increased preneoplastic hepatic lesions in rats.48 However, while low-protein diets decrease hepatocarcinogenicity, they appear to predispose patients to a subacute EXTRA See for information on assessing liver function in dogs. 650 October 2007 VETERINARY MEDICINE http://www.fda.gov/bbs/topics/NEWS/2005/NEW01290.html http://www.fda.gov/bbs/topics/NEWS/2005/NEW01290.html http://www.vetstreamcanis.com/ACI/October/VMD1/fre00120.asp

Table of Contents Feed for the Digital Edition of Veterinary Medicine - October 2007

Veterinary Medicine - October 2007 Contents Leading Off The Veterinary Medicine Interview: Dr. Kevin Fitzgerald Toxicology Brief Idea Exchange Animal Sheltering in the United States: Yesterday, Today, and Tomorrow The Euthanasia Problem Offer Basic Behavior Counseling for Every Pet at Every Visit Promote and Perform Early Spaying and Neutering Assist Owners in Selecting the Best Pets for their Lifestyles Champion Animal Welfare in Your Community CE Form Product Review Advertiser Index Marketplace/Classifieds Mind Over Miller

Veterinary Medicine - October 2007

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