Effect of N-Acetylcysteine Supplementation on Intracellular Glutathione, Urine Isoprostanes, Clinical Score, and Survival in Hospitalized Ill Dogs

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 48hours 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=30) versus placebo (n=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 55g/mL; P=.0005) as well as elevated IP/Cr ratios (872 versus 399pg/mg; P=.0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1M; P<.0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44mM; P=.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 48hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.