Peripheral markers of oxidative stress in Labrador retrievers with copper-associated hepatitis.

Abstract

OBJECTIVES: To evaluate biomarkers of oxidative stress in dogs with copper-associated hepatitis (CAH) as compared with healthy controls, and to evaluate if these markers correlate with hepatic copper concentrations and hepatic histopathologic features. MATERIALS AND METHODS: Prospective study. Plasma reactive metabolite concentrations, plasma antioxidant potential, and plasma and urine isoprostane concentrations were determined in Labrador retrievers with copper-associated hepatitis (n=9) as well as in breed- and sex-matched (n=9) and age- and sex-matched (n=9) healthy control populations. Possible correlations between markers of oxidative stress and hepatic histopathological features also were investigated. RESULTS: Reactive metabolites (median, range) were over twofold greater in dogs with copper-associated hepatitis (87.2 RFU/μL, 60.9 to 185.6 RFU/μL) as compared to breed- and sex-matched (38.2 RFU/μL, 22.4 to 116.8 RFU/μL) and age- and sex-matched controls (32.0 RFU/μL, 18.5 to 127.4 RFU/μL). Antioxidant potential was decreased in copper-associated hepatitis dogs (6.5 TE/μL, 5.1 to 7.7 TE/μL) as compared to breed- and sex-matched controls (8.2 TE/μL, 5.3 to 11.8 TE/μL). Both reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio were positively correlated with hepatic copper concentrations. Plasma and urine isoprostanes were variable and not significantly different between populations. CLINICAL SIGNIFICANCE: Labrador retrievers with copper-associated hepatitis have altered oxidant status. Plasma reactive metabolite concentrations and the reactive metabolite to antioxidant potential ratio could be useful biomarkers. However, neither plasma nor urine isoprostanes were useful biomarkers for copper-associated hepatitis.