HEPATIC HISTOLOGIC LESIONS
Histologic examination of liver biopsy samples reveals hepatocellular fatty vacuolation, hepatic necrosis, periportal necrosis,
portal fibrosis, and perivenular necrosis and inflammation. Bile duct proliferation is present, and bile canaliculi may be
plugged with bile casts.4,13,15-18
FOOD OR TISSUE ANALYSIS
Consider aflatoxicosis in any dog presenting with signs of acute liver failure, especially when the history is suggestive
of a toxin (e.g. multiple dogs in same household affected, recent change in food). Since clinical signs are nonspecific for aflatoxicosis,
a definitive diagnosis requires analyzing suspect food or identifying toxins in tissue samples. Several veterinary diagnostic
laboratories offer qualitative or quantitative tests for aflatoxin in feed. Tissue analysis is less available. A list of accredited
diagnostic laboratories is provided online by the American Association of Veterinary Laboratory Diagnosticians at
http://www.aavld.org/mc/page.do?sitePageId=33930. Aflatoxins can be identified in urine, but metabolites are quickly cleared from the body, making postexposure detection
difficult.19
TREATMENT
Table 1: Treatment Considerations in Dogs with Aflatoxicosis
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Because no specific antidote for aflatoxins is available, treatment is aimed at supportive care and the management of specific
hematologic and biochemical derangements (Table 1).
Detoxification
Aflatoxins typically do not produce signs of toxicosis until after they have been absorbed from the gastrointestinal tract.
So unless the dog has a recent history of ingestion of a known aflatoxin-contaminated food (which is rarely the case), emetics
and other gastrointestinal decontamination methods are not indicated. Once absorbed, aflatoxins are rapidly metabolized in
the liver. Interaction with cytochrome p450 results in toxic metabolites that are then conjugated with glutathione (GSH).
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 0.2-μm 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 decrease cholestasis and fibrosis in people
and nonhuman primates with liver disease.28
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