Fatty liver and anti-oxidant enzyme activities along with peroxisome proliferator-activated receptors γ and α expressions in the liver of Wilson's disease.

BACKGROUND

The mechanisms of liver damage and steatosis in Wilson's disease (WD) presenting accumulation of copper generating oxidants remain unclear. Recent studies have shown that peroxisome proliferator-activated receptors (PPARs), in particular PPARs α and γ, regulate fat content of the liver together with the anti-oxidant and anti-inflammation systems. However, such PPARs have never been studied in WD.

METHODS

We examined PPARs along with the liver damage and steatosis of WD using liver specimens from affected patients exhibiting mild liver damage (group I, n = 5), moderate or greater liver damage (group II, n = 10) and fulminant hepatic failure (group III, n = 5), and from asymptomatic carriers (group H, n = 4).

RESULTS

PPAR α expression was increased over the control levels in groups H and I but was decreased in groups II and III in parallel with the progression of liver damage (group H = I>II>III). PPAR γ expression was inversely increased (group H<I<II<III). Mn-dependent superoxide dismutase (Mn-SOD), CuZn-SOD, and catalase activities were decreased in the affected three groups, and were increased in group H. Among group II exhibiting substantial inter-individual variances in parameters, the severity of steatosis showed a significant positive correlation with PPAR γ expression (p<0.001) but not PPAR α expression. CuZn-SOD activity was positively correlated with PPARα expression (p<0.05) but not PPAR γ expression.

CONCLUSION

These results suggest that changes of PPARs γ and α are associated with the steatosis and the impairment of anti-oxidant system in the liver of WD.