The use of antioxidants as part of the treatment regimen of liver disease in veterinary medicine has become increasingly popular over recent years. Antioxidants that may have a role in the treatment of liver disease include S-adenosylmethionine [SAMe], silybin, vitamin E and vitamin C.

A free radical is a molecule containing one or more unpaired electrons in their outer orbit. In an effort to maintain electron balance, these free radicals will steal electrons from neighbouring molecules, which prevents the molecule from functioning normally. This can result in cell membrane damage, DNA mutations and fibrosis.

Antioxidants and importance of glutathione

In order to protect itself from damage, the liver has developed a complex antioxidant defence system. Antioxidants act by donating spare electrons and thus neutralising the free radicals. In a healthy individual, free radical levels are balanced by antioxidant production.

Glutathione (GSH) is the body’s major antioxidant and studies have shown that hepatic glutathione levels are depleted in dogs and cats with liver disease.

Oxidative stress

Oxidative stress is defined as an imbalance between free radicals and antioxidant defence systems (such as an overproduction of free radicals or a depletion of the body’s endogenous antioxidant defence systems). Oxidative stress is increased in cases of liver disease owing to the effects of inflammation, reduced blood flow and mitochondrial damage by toxins, drugs or bile acids.

S-adenosylmethionine (SAMe)

SAMe is an endogenous molecule formed from the amino acid L-methionine and ATP by the enzyme SAMe synthetase and initiates three metabolic pathways (Figure 1):

1.   transmethylation – one of the most important transmethylation reactions involves the synthesis of cell membrane phospholipids, thus maintaining cell membrane fluidity and function.

2.   transsulphuration – SAMe is converted into glutathione via homocysteine and cysteine. Glutathione is the major antioxidant within the body.

3. aminopropylation – SAMe is decarboxylated to produce polyamines which promote DNA and protein synthesis, necessary for normal hepatocyte growth and repair.

Bioavailability of SAMe

The bioavailability of oral SAMe is low, and food has been shown to interfere with its absorption. It is, therefore, recommended that SAMe should be administered on an empty stomach. It can also be oxidised into an inactive form unless it is manufactured with an enteric-coating or the SAMe itself is microencapsulated.

Indications and recommended dose

SAMe is indicated in any type of liver disease, but especially toxic hepatitis and biliary stasis. In addition, it may also have a role in the treatment of paracetamol toxicity in cats.

Silybin

Silymarin is an extract of the milk thistle plant, Silybum marianum, which has been used for centuries as a herbal remedy for liver disease. Silymarin contains four flavonoids, of which silybin is the most biologically active isomer. Silybin is a strong free-radical scavenger as well as an anti-inflammatory.

Summary

Although there is currently restricted evidence as to their efficacy in clinical situations, antioxidants are indicated in most acute or chronic hepatopathies. Together with drugs and dietary manipulation, antioxidants are increasingly being used for the management of liver disease in dogs and cats.

Author

James Kyffin BVSc (Hons) MRCVS

• VOL 26 • August 2011 • Veterinary Nursing Journal