Purpose: Wilson's disease (WD) is an inherited disorder involving copper accumulation in the liver and brain. An important mechanism responsible for hepatocyte injury in WD is mitochondria destruction, although damage may also be caused by oxidative stress and lipid peroxidation.
Patients/methods: The study included 54 treated patients with WD without liver cirrhosis and 10 healthy controls. All patients had liver biopsy and immunohistochemical analysis of liver samples was performed using targeted staining for markers of mitochondrial injury (thioredoxin-2 [TRX2], cytochrome c oxidases subunit 2 [COX2], and cytochrome c oxidases complex IV subunit 4 isoform 1 [COX4-1]), of oxidative stress (peroxiredoxin-1 [PRDX1] and 8-hydroxyguanosine [8-OHdG]), and of lipid peroxidation (4-hydroxynonenal [4-HNE]).
Results: Expression, measured as mean strengths of intensity (SI) of immunohistochemical reactions per 5 fields of view, was significantly lower in patients with WD compared to controls for COX2 (2.9 vs 8.3), 8-OHdG (0.05 vs 3.8), TRX2 (4.9 vs 10.1), and PRDX1 (4.6 vs 10.1) (all P < 10-5). COX4-1 expression was undetected in patients with WD but detected in control specimens (8.1) (P < 10-5). 4-HNE was overexpressed in patients with WD compared to controls (10.1 vs 9.1; P < 0.07).
Conclusions: Negligible COX4-1 and low COX2 expression in liver specimens may serve as markers of inner mitochondrial membrane injury in treated patients with WD and early stages of liver fibrosis.
Keywords: Copper; Liver fibrosis; Mitochondria; Wilson's disease.
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