Effect of N-acetylcysteine supplementation on intracellular glutathione, urine isoprostanes, clinical score, and survival in hospitalized ill dogs.

Abstract

BACKGROUND: Antioxidant depletion and lipid peroxidation have been correlated with disease severity and associated with poor outcomes. HYPOTHESIS/OBJECTIVES: Supplementing dogs with N-acetylcysteine (NAC) during the first 48&#xa0;hours of hospitalization will increase cysteine, normalize glutathione concentrations, and decrease the degree of lipid peroxidation associated with illness. ANIMALS: Sixty systemically ill hospitalized client-owned dogs and 14 healthy control dogs. METHODS: Randomized investigator-blinded, placebo-controlled prospective study. Dogs were randomized to treatment with NAC (n&#xa0;=&#xa0;30) versus placebo (n&#xa0;=&#xa0;30). Antioxidants, urine 8-isoprostane/creatinine (IP/Cr), and clinical score were determined before and after treatment with NAC. Glutathione, cysteine, and vitamin E concentrations were quantified using high-performance liquid chromatography. Atomic absorption spectroscopy and enzyme-linked immunosorbent assays were used to quantify selenium and isoprostane concentrations, respectively. RESULTS: Ill dogs had significantly lower vitamin E concentrations (27 versus 55&#xa0;&#x3bc;g/mL; P&#xa0;=&#xa0;.0005) as well as elevated IP/Cr ratios (872 versus 399&#xa0;pg/mg; P&#xa0;=&#xa0;.0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1&#xa0;&#x3bc;M; P&#xa0;<&#xa0;.0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44&#xa0;mM; P&#xa0;=&#xa0;.0463). Illness severity and survival were unchanged after short duration NAC supplementation. CONCLUSIONS: Ill dogs experience systemic oxidative stress. Supplementation with NAC during the first 48&#xa0;hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.