Antioxidant Drugs and S-Adenosyl-L-Methionine:
Most if not all damage to the liver, regardless of cause, is mediated by increased production of free radicals that cause oxidative damage to cell organelles. Recent studies indicate that antioxidant therapy is beneficial in some types of chronic hepatitis. For this reason, treatment with an antioxidant drugs to scavenge free radicals might be protective against oxidant injury to hepatocytes, particularly in patients with copper accumulation.
S-Adenosyl-L-Methionine (DenosylŽ)
Glutathione (GSH) is a major hepatic antioxidant and is necessary for hepatic detoxification of drugs and toxins. S-adenosly-L-methionine (SAMe) is a precursor or GSH and is important in the maintaining normal hepatocyte membrane functions and hepatocyte regenerative processes. GSH concentration is decreased in patients with both acute and chronic liver diseases. Conversion of methionine to SAMe, and subsequently to GSH, is also impaired. The effects of this may include methionine intolerance and accumulation of oxidants, thereby leading to worsening of the liver damage.
Treatment of human cirrhosis patients with oral SAMe results in increased plasma concentration of GSH, cysteine and taurine; and a decrease in plasma methionine, serum bile acids and bilirubin and ALT and GGT activities. Cholestatic disease associated with oral contraceptives, alcoholic hepatitis, and druginduced hepatotoxicity (e.g. acetaminophen, anticonvulsants) improve significantly when treated with SAMe. SAMe attenuates alkaline phosphatase induction and improves glutathione production in dogs given chronic high dose glucocorticoid therapy.
Several preparations of this neutraceutical are available over-the-counter, but potency is variable.
Denosyl SD4 (Nutramax Laboratories, Inc., Edgewood, Maryland) is recommended.
The recommended dose is 20 mg/kg/day given should be given on an empty stomach Conditions for which SAMe use should be considered include feline hepatic lipidosis, feline cholangitis and cholangiohepatitis, and in dogs with marked vacuolar hepatopathy from either glucocorticoid administration or idiopathic vacuolar hepatopathy, and in chronic active hepatitis.There are no known side effects in animals.
Vitamin E (d-alpha tocopherol) has been shown to protect the liver from copper-related oxidant damage and from oxidant damage caused by accumulation of hydrophobic bile acids that accumulate in cholestatic liver disease. Vitamin E is inexpensive and safe, and is recommended for use in dogs with any type of chronic hepatitis. The recommended dose is 50 - 400 IU/day.
Silymarin is a flavonolignan found in milk thistle which has been used as a natural remedy for hepatobiliary disease. Flavonolignans are reported to have antioxidant properties by scavenging for freeradicals that cause lipid membrane damage. Results of controlled studies in humans using milk thistle to treat patients with acute and chronic liver diseases are variable, but some evidence does indicate beneficial effects from this treatment. One study in beagles showed that dogs pre-treated with milk thistle were protected from the toxic effects of amanita mushroom poisoning, whereas placebo-treated dogs died. Limited studies and clinical experience preclude making firm recommendations regarding the use of milk thistle to treat chronic liver disease. Dosages extrapolated from human use range from 50 - 250 mg/kg/day.
Many over-the-counter products are available; potency varies. Recently, Nutramax released a new veterinary product, called MarinŽ which contains silybin, vitamin E, and zinc in a single tablet formulation. A formulation of MarinŽ for cats contains silybin and vitamin E only. Silybin is the most active component of silymarin, derived from the milk thistle.