Effects of lipoic acid in cats: Pharmacokinetics, toxicity, and antioxidant activity.

摘要

Lipoic acid (LA), an endogenous Krebs cycle cofactor, is reported to be an antioxidant for humans, rodents, and dogs. LA has been fed by owners to pets and added to some commercial dog foods. The effects of LA in cats were studied. (1) For comparison, effectiveness of known antioxidants was tested by administering cysteine, vitamin C, or vitamin E to adult cats followed by oxidant challenges with onion powder or propylene glycol. Blood GSH increased in the cysteine group, and Heinz body percentage was lower in all antioxidant-supplemented cats. (2) Pharmacokinetics for LA were compared in cats and dogs after IV and oral administration. LA plasma half-life was twice as long and fractional availability half as much in cats as in dogs. Volume of distribution included all body water in dogs but only plasma in cats. Urinary excretion was cyclic in both species and accounted for 80% and 20% of the administered dose in dogs and cats, respectively. Fecal excretion was 2% in both species. (3) Acute toxicity of oral LA included: clinical signs of anorexia, hypersalivation, ataxia, and hypersensitivity; histological findings of hepatocellular damage; and elevated serum ammonia and decreased ratios of plasma branched chain to aromatic amino acid concentrations. Bile was the major excretory route for LA, which was >98% protein bound. (4) Effectiveness of supplemental antioxidants was tested by adding vitamin E + cysteine, LA, or all 3 antioxidants to a control diet for 25 weeks, then administering oral acetaminophen as an oxidant challenge. Consuming LA was associated with transiently increased lymphocyte blastogenesis, but also lower whole blood GSH, higher methemoglobinemia, DNA damage, and clinical signs compared to controls after acetaminophen challenge. Cats receiving vitamin E + cysteine showed lower damage to proteins. Conclusions: Vitamin E and cysteine supplementation may provide some antioxidant protection in cats. In dogs, LA kinetics resembled those reported in humans and rodents, but cats had higher first-pass liver uptake and plasma retention. LA is hepatotoxic to cats at 114 the dose reported in dogs. In cats, LA was not an effective antioxidant when supplemented at 150-mg/kg of diet.