Copper induced hemolysis

Death of hepatic cells may be so massive that severe hepatitis may end the patient s life within weeks of the first clinical symp-ton. Even when the hepatitis is not fatal it is often accompanied by the release into blood of sufficient copper from damaged hepa-tocytes to cause copper-induced hemolysis of so many erythrocytes that anemia results J). 

How copper induces hemolysis is not known, but at least two mechanisms have been proposed. Copper... 

Symptoms in patients with Wilson s disease usually begin in the second or third decade of life, but may be earlier or later. However, mutations that completely destroy gene function may be associated with onset of liver disease as early as 3 years of age. The initial clinical presentation may be hepatic, with presentation similar to acute hepatitis or to chronic active hepatitis neurological (e.g., clumsiness, dysarthria, ataxia, and tremors) renal (renal tubular acidosis with aminoaciduria) or, less commonly, hematological, with hemolysis secondary to acute release of free copper from tissue and subsequent oxidation of erythrocyte membranes. The hepatic, and possibly CNS, damage may also be secondary to copper-induced oxidative damage to mitochondrial membranes. Hepatic levels of Cp messenger ribonucleic acid (mRNA) are reduced in patients with Wilson s disease, probably secondary to inhibition of transcription by increased intracellular levels of apoCp. ... 

In 1989, we showed [142] that the Fe2+(rutin)2 complex is a more effective inhibitor than rutin of asbestos-induced erythrocyte hemolysis and asbestos-stimulated oxygen radical production by rat peritoneal macrophages. Later on, to evaluate the mechanisms of antioxidant activities of iron rutin and copper-rutin complexes, we compared the effects of these complexes on iron-dependent liposomal and microsomal lipid peroxidation [165], It was found that the iron rutin complex was by two to three times a more efficient inhibitor of liposomal peroxidation than the copper-rutin complex, while the opposite tendency was observed in NADPH-dependent microsomal peroxidation. On the other hand, the copper rutin complex was much more effective than the iron rutin complex in the suppression of microsomal superoxide production, indicating that the copper rutin complex indeed acquired additional SOD-dismuting activity because superoxide is an initiator of NADPH-dependent... 

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