Page 1129 - Small Animal Clinical Nutrition 5th Edition

Hepatobiliary Disease 1175

Antioxidant Vitamins E and C plements for dogs with inflammatory liver disease (Rolfe and
VetBooks.ir Lipid peroxidation may be involved in the pathogenesis of Twedt, 1995).
Alkenals (malondialdehyde and 4-hydroxyalkenals) in blood
some forms of acute liver injury and chronic hepatitis (Scalfani
or tissues indicate lipid peroxidation, which may be a result of
et al, 1986). Free radicals are an important component of most
forms of liver damage. Abnormal concentrations of bile acids in vivo oxidative reactions. Alkenals are sometimes measured to
and the accumulation of heavy metals, such as copper and iron, determine the effectiveness of antioxidant interventions. Al-
cause free radical generation in the liver (Sokol and Hof- though dietary levels of antioxidant vitamins needed to reduce
fenberg, 1996; Sokol et al, 1994; Twedt et al, 1998). Activated serum alkenal levels in dogs and cats with liver disease have not
inflammatory cells, damaged hepatocyte mitochondria and been established, a study found that food levels of 445 and 540
release of cytochrome P450 enzymes contribute to the produc- IU of vitamin E/kg (as fed basis) were necessary to reduce
tion of reactive oxygen species. As the cascade proceeds, further serum alkenal concentrations in apparently healthy dogs and
hepatocyte damage occurs due to subsequent oxidation of cel- cats, respectively (Jewell et al, 2000). Until more specific data
lular lipids, proteins and DNA. Oxidative stress may also acti- are available, foods for canine and feline liver patients should
vate pro-apoptotic protein kinases, proinflammatory transcrip- provide at least 400 and 500 IU/kg DM, respectively.
tion factors and modulators of apoptosis (Medina and Mor- Vitamin C is important for regenerating oxidized vitamin E.
eno-Otero, 2005). Foods for canine liver disease patients should contain at least
Vitamin E functions as a cellular membrane-bound antiox- 100 mg vitamin C/kg DM; foods for feline liver disease patients
idant that protects membrane phospholipids from oxidative should contain 100 to 200 mg vitamin C/kg DM. This recom-
damage. Results of vitamin E supplementation studies in hu- mendation is based on the vitamin E levels in foods for dogs and
man liver disease patients have been inconsistent. Vitamins E cats with liver disease and data that show vitamin C regenerates
and C improved fibrosis scores in patients with nonalcoholic vitamin E at about a 1:1 molar ratio (Barclay et al, 1985). Also,
steatohepatitis (Harrison et al, 2003). Results of animal stud- this range is not a risk for urinary oxalate production (Yu and
ies have also been mixed, perhaps due study design issues. Gross, 2005).
However, in a study using a rat model of steatocholestasis, sub- The earlier antioxidants are used to manage the oxidative
cutaneous vitamin E provided significant protection against damage that accompanies acute and chronic hepatobiliary dis-
bile acid-induced hepatic injury, including a reduction in the ease, the more likely they are to be effective.
release of apoptosis-inducing factor. Bile acid-induced necrot-
ic hepatocyte injury was responsive to vitamin E therapy (So- L-Carnitine
den et al, 2007). Bedlington terriers with copper-associated Food and hepatic biosynthesis are the primary sources of L-car-
hepatopathy have oxidative damage in their mitochondria and nitine for animals. L-carnitine transports long-chain fatty acids
reduced mitochondrial vitamin E concentrations (Sokol et al, across the inner mitochondrial membrane into the mitochondr-
1994). Vitamin E has a protective effect in the liver from cop- ial matrix for β-oxidation. L-carnitine also removes potentially
per-related oxidant damage and bile acids (Gaetke and Chow, toxic acyl groups from cells and equilibrates ratios of free
2003; Sokol et al, 1998). In a study using 20 dogs with natu- CoA/acetyl-CoA between the mitochondria and cytoplasm.
rally occurring chronic hepatitis fed a vitamin E-supplement- Obesity is a risk factor for feline hepatic lipidosis; several stud-
ed food for three months, increases in serum and hepatic vita- ies have investigated the relationship between L-carnitine,
min E concentrations were accompanied by an increased weight loss in obese cats and feline hepatic lipidosis. Mean con-
hepatic reduced glutathione to oxidized glutathione (GSH: centrations of L-carnitine in plasma, liver and skeletal muscle
GSSG) ratio, suggesting an improved hepatic redox status. were significantly greater in cats with idiopathic hepatic lipidosis
However, no changes in clinical or histologic scores were noted than in control cats (Jacobs et al, 1990). These findings suggest
(Twedt et al, 2003). that systemic L-carnitine deficiency does not appear to con-
Vitamin C is an important soluble intracellular antioxidant tribute to the pathogenesis of feline idiopathic hepatic lipidosis.
that helps convert oxidized vitamin E back to its reduced, active However, other studies have shown that feline foods supple-
form. Vitamin C is also necessary for the synthesis of L-carni- mented with L-carnitine benefit obese cats undergoing rapid
tine, which is important for transport of long-chain fatty acids weight loss. Dietary L-carnitine supplementation protected o-
across the mitochondrial membrane. People with liver disease bese cats from hepatic lipid accumulation during caloric restric-
often have low hepatic vitamin C concentrations, in part tion and rapid weight loss (Armstrong et al, 1992). Foods sup-
because human beings are unable to synthesize vitamin C, plemented with L-carnitine can safely facilitate rapid weight loss
unlike dogs and cats. Although vitamin C supplementation in obese cats (Center et al, 1997). Based on these studies, the use
may be beneficial in treating liver disease, supplementation of L-carnitine supplements or L-carnitine supplemented foods
with excessive amounts of vitamin C may be deleterious in seems appropriate for obese cats undergoing weight reduction.
patients with increased hepatic copper or iron concentrations. Besides being of value in preventing hepatic lipidosis, L-
No specific dosages of vitamins E and C have been docu- carnitine supplementation may also benefit cats with hepatic
mented to be safe and effective for dogs with liver disease. lipidosis (Center, 1996c). One author has recommended a
However, 50 to 400 IU vitamin E/day and 500 to 1,000 mg dose of 250 to 500 mg L-carnitine/day for cats with hepatic
vitamin C given per os daily have been recommended as sup- lipidosis (Center, 1996c). Others have found that lower doses