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Wilson disease (WD) is an autosomal recessive disorder due to the defect in ATP7B gene characterized by excessive accumulation of copper in the liver with progressive hepatic damage and subsequent redistribution to various extrahepatic tissues including the brain,kidneys,and cornea. Strikingly,the total serum copper concentration is always low in WD,even though the non-ceruloplasmin copper level is still expected to be high.To assess the role of free radical reactions catalyzed by nonceruloplasmin copper,we investigated erythrocyte metabolism and oxidative stress as a mechanism for hemolysis in eight WD patients during episodes of acute hemolysis and compared them with eight follow-up cases of WD on D-penicillamine therapy and eight healthy,age-matched children. Elevated levels of non-ceruloplasmin copper were found in all the WD patients during an episode of hemolytic anemia. There was marked inhibition in erythrocyte enzymes,namely,hexokinase,totaladenosine triphosphatase (ATPase),and glucose-6-phosphatedehydrogenase (G-6-PD) from WD patients compared with patients on penicillamine and healthy children,indicating altered erythrocyte metabolism during a hemolytic crisis. Antioxidant status was also found to be compromised as is evident from decreased glutathione (GSH) levels,decreased antioxidantenzymes (namely,superoxide dismutase,catalase,glutathioneperoxidase,and glutathione reductase),increased lipid peroxidation,and deranged plasma antioxidants. Uric acid showed maximum decrease followed by ascorbic acid. These finding ssuggest that the free radical production by elevated non-ceruloplas- min copper through transition metal catalyzed reactionsleads to oxidative injury resulting in altered erythrocyte metabolism and severely compromised antioxidant status of WD patients during hemolytic anemia.
Wilson disease (WD) is an autosomal recessive disorder due to defect in ATP7B gene characterized by excessive accumulation of copper in the liver with progressive hepatic damage and subsequent redistribution to various extrahepatic tissues including the brain, kidneys, and cornea. Strikingly, the total serum copper concentration is always low to WD, even though the non-ceruloplasmin copper level is still expected to be high. Assessment of the role of free radical reactions catalyzed by nonceruloplasmin copper, we investigated erythrocyte metabolism and oxidative stress as a mechanism for hemolysis in eight WD patients during episodes of acute hemolysis and compared them with eight follow-up cases of WD on D-penicillamine therapy and eight healthy, age-matched children. Elevated levels of non-ceruloplasmin copper were found in all the WD patients during an episode of hemolytic anemia. there was marked inhibition in erythrocyte enzymes, namely, hexokinase, totaladenosine triphosphatase (ATPase), an d Glucose-6-phosphate dehydrogenase (G-6-PD) from WD patients compared with patients on penicillamine and healthy children, indicated altered erythrocyte metabolism during a hemolytic crisis. Antioxidant status was also found to be as evident from decreased glutathione (GSH ) levels, decreasing antioxidantenzymes (namely, superoxide dismutase, catalase, glutathioneperoxidase, and glutathione reductase), increased lipid peroxidation, and deranged plasma antioxidants. These finding ssuggest that the free radical production by elevated non- -ceruloplas- min copper through transition metal catalyzed reactionsleads to oxidative injury resulting in altered erythrocyte metabolism and severely compromised antioxidant status of WD patients during hemolytic anemia.