Veterinary Medicine - October 2007 - (Page 647)

Toxicology Brief PEER-REVIEWED Dose-dependent hepatocellular injury occurs from the production of free radicals that cause oxidative damage. Epoxide metabolites of aflatoxins can also bind and disrupt DNA, leading to hepatocellular carcinoma. The potential for damage from aflatoxins is long-term; toxins may remain bound to circulating albumin for up to two months.10,20,21 While specific antidotes for aflatoxins have not been found, several treatments may augment the metabolism and excretion of the toxins. Detoxification of the damaging aflatoxin epoxide occurs via conjugation with hepatic GSH10,21,22; therefore, administering medications that promote hepatic GSH synthesis may increase a dog’s capacity to metabolize and excrete aflatoxins. Medications and vitamins that affect GSH stores or that have hepatoprotective effects include • N-acetylcysteine. N-acetylcysteine is thought to replenish GSH stores by acting as a GSH substitute and precursor. In addition, N-acetylcysteine has beneficial effects on liver blood flow, oxygen extraction, and the formation of nonglutathione products that protect against cell injury.23 Experimentally, N-acetylcysteine has protective effects against aflatoxin damage in chickens, rats, and rabbits.24-26 A 5% solution (the 20% solution can be diluted 1:4 with sterile water or saline solution) is administered intravenously (over 20 minutes) or orally. Products not labeled for intravenous use require a 0.2µm syringe filter. A loading dose of 140 mg/kg is given intravenously once followed by a maintenance dose of 50 to 70 mg/kg given intravenously every four to six hours for one to three days.27 • S-adenosylmethionine (SAMe). SAMe is a supernutrient (a nutrient that must be provided exogenously when endogenous synthesis is impaired or insufficient) used to increase the availability of precursors for GSH synthesis. It also acts as a methyl donor and enzyme activator for key reactions that maintain membrane structure and function. SAMe has been shown to loides hepatotoxicoisis in dogs).30 Nutramax Laboratories offers the oral veterinary product Marin (silybin/vitamin E/zinc) in two tablet sizes that contain either 24 or 70 mg silybin. The product information for Marin indicates a low mg/kg dose of silybin; instructions are given for Administering medications that promote hepatic glutathione synthesis may increase a dog’s capacity to metabolize and excrete aflatoxins. decrease cholestasis and fibrosis in people and nonhuman primates with liver disease.28 The recommended dosage in dogs is 17 to 20 mg/kg given orally once a day as needed for weeks to months.29,30 Denosyl (Nutramax Laboratories) and Zentonil (Vétoquinol) are SAMe veterinary products that each offer three tablet sizes. Ideally, these products should be given on an empty stomach to increase absorption.31,32 • Milk thistle (silymarin). The silybinphosphatidylcholine complex in silymarin enhances GSH production and prevents bioactivation of certain toxins. Silymarin may also protect normal hepatocytes, promote the regeneration of hepatocytes, and act as a free-radical scavenger and antioxidant.33 Specifically, silymarin has been reported to have hepatoprotective effects against aflatoxicosis in chickens and rats.34,35 A standard therapeutic dosage for silymarin has not been established in dogs; recommendations range from 7 to 15 mg/kg/day (based on human data) to 50 to 150 mg/kg/day (based on Amanita phalweight ranges with doses varying from about 1.5 to 4.5 mg/kg once a day depending on a dog’s size.36 If a higher dose is desired, Marin would have to be administered extra-label. Although Marin also contains zinc and vitamin E, the zinc content in the product is low and the safety margin for vitamin E is high. Denamarin (Nutramax Laboratories) is also available and contains a combination of SAMe and silybin. • Vitamin E. Vitamin E is a fat-soluble vitamin that may have a protective effect in aflatoxin exposure by counteracting the formation of lipid peroxides. Vitamin E supplementation in rabbits fed aflatoxin resulted in fewer and less severe changes in liver enzymes and other biochemical parameters as compared with a control group.37 Because of biliary obstruction, oral absorption of vitamin E may be decreased in aflatoxicosis. The recommended dosage is 100 to 400 IU given orally twice a day.38 Marin contains vitamin E and comes in two tablet sizes that contain 105 or 300 IU vitamin E.36 • L-carnitine. L-carnitine is an amino acid derivative synthesized primarily VETERINARY MEDICINE October 2007 647

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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