Mechanisms of Hemolysis Induced by Copper

Abstract

An excess of copper is the cause of hemolysis in a number of clinical conditions. Incubation of human erythrocyte (RBC) suspensions with copper (II) causes the formation of methemoglobin, lipid peroxidation and hemolysis. A new variant of the thiobarbituric acid (TBA) method, which minimizes the formation of interfering chromophores, was used to detect lipid peroxidation. Lipid peroxidation precedes hemolysis and the antioxidant vitamins C and E, which inhibit lipid peroxidation, also inhibit hemolysis. Consequently lipid peroxidation appears to be the cause of RBC destruction. Lipid peroxidation arises mostly from the oxidation of oxyhemoglobin by copper as it is inhibited in RBCs with carbon monoxyhemoglobin or methemoglobin. A direct interaction of copper with the red cell membrane seems to play only a minor role. Copper effects depend on the presence of free SH groups. Lipid peroxidation is probably initiated by activated forms of oxygen as it is increased by an inhibitor of catalase and reduced by hydroxyl radical scavengers. With higher copper concentrations hemolysis is greater: its mechanism appears different as lipid peroxidation is smaller but hemoglobin alterations, namely precipitation, are more pronounced.

The Effects of Copper Sulfate on Liver Histology and Biochemical Parameters of Term Ross Broiler Chicks

“…The samples were then centrifuged at 1,000×g for 5 min, and 0.5 ml of the resultant supernatants was added to 2 ml Na 2 HPO 4 and 0.5 ml Ellman reactive (dithiodinitrodibenzoic acid, sodium citrate, distilled water). The absorbance of the supernatants were recorded at 412 nm and compared with those obtained from GSH standards [13].…”

“…Copper has also been shown to induce hemolysis [13,14], with copper sulfate poisoning resulting in hepatotoxicity, acute renal failure, and gastrointestinal bleeding [15]. Strong evidence also exists for hepatic free radical production in animal models of copper overload, ethanol consumption, and ischemia reperfusion [16].…”

Inhibitory effects of Ougi-keishi-gomotsu-to, a traditional herbal medicine, on lipid peroxidation and protein oxidative modification

“…Free radicals induced by copper produce alteration of the myocardial membrane protein (Parinandi et al, 1991), DNA damage (Yamamoto and Kawanishi, 1989;Dean et al, 1989), LPO of erythrocyte membranse (Chan et al, 1982;Fernandes et al, 1988) and oxidation of low density protein (Halvorsen et al, 1996). Free serum copper is increased in Wilson's disease and catalysed free radical reactions.…”

Inhibitory effects of Astragali Radix, crude drug in Oriental medicines on lipid peroxidation and protein oxidative modification of mouse brain homogenate by copper

“…As shown in Table 2, the IC 50 of Astragali Radix was 74.5 mg/mL (Table 2). Free radical induced by copper produces LPO of the erythrocyte membrane (Chan et al, 1982;Fernandes et al, 1988) and oxidation of low density protein (Halvorsen et al, 1996). Free serum copper is increased in Wilson's disease and in catalysed free radical reactions.…”