Immunohistochemical Expression of Oxidative Stress and Apoptosis Markers in Archived Liver Specimens from Dogs with Chronic Hepatitis.

ABSTRACT

Chronic hepatitis (CH) in dogs is histologically characterized by an inflammatory infiltration of the liver accompanied by hepatocellular apoptosis or necrosis, varying degrees of fibrosis and regeneration. Oxidative stress has been suggested to play a role in the pathogenesis of various liver diseases, including CH. This study assessed the immunohistochemical expression of markers of oxidative stress (4-hydroxynonenal [4-HNE] and malondialdehyde [MDA]) and apoptosis (active caspase-3 [casp-3]) in 35 surplus archived formalin-fixed paraffin-embedded liver biopsies from 25 dogs with CH and 10 control dogs that had no significant hepatic changes. Correlations between immunohistochemical markers and necroinflammatory, fibrosis and histological copper scores, and hepatic copper concentrations were also determined. There were no significant differences in 4-HNE expression between the two groups. Control dogs had lower hepatic MDA scores than dogs with CH. MDA scores were positively correlated with copper scores as well as hepatic copper concentrations. There was no significant difference in casp-3-positive hepatocytes between groups. However, a positive correlation between casp-3 immunoreactivity and copper scores, as well as hepatic copper concentrations, was identified. Necroinflammatory and fibrosis scores were positively correlated with immunoreactivity for MDA and casp-3. MDA and casp-3 are expressed in canine liver and both markers are correlated with necroinflammatory scores, fibrosis scores and hepatic copper accumulation. Our results suggest the utility of immunolabelling for MDA and casp-3 for assessment of hepatic oxidative stress and apoptosis, respectively, in dogs with CH.