INTERACTIONS OF MODIFIED HEMOGLOBINS WITH IRON CHELATORS

点击翻译按钮获取中文摘要

Among the current strategies aimed at decreasing the oxidant effect of HBOCs is the use of iron chelators to prevent the potential molecular and cellular damage caused by iron induced oxygen free radicals. We studied the effects of interactions of desferrioxamine and a newly developed pyrone, ethyl maltol, on the rate of autoxidation and hydrogen peroxide mediated oxidation of cross-linked hemoglobins. There was a slight decrease in both the rate of autoxidation and hemichrome formation when ethyl maltol was included in the solutions containing these hemoglobins. Conversely, inclusion of desferrioxamine led to an increase in oxidation products. In the reaction mixture and in the presence of excess hydrogen peroxide, desferrioxamine led to a 20-30 % rise in methemoglobin coupled with a slight reduction in the hemichrome formation. Ethyl maltol, on the other hand, has little or no effect. It appears that unlike ethyl maltol, desferrioxamine, independent of its chelating properties, acts as an oxidizing agent. This may relate to its ability to interact directly with oxygen free radicals resulting in increased methemoglobin formation. The observed relative differences in the susceptibility of cross-linked hemoglobins to the prooxidant activity of desferroxamine may reflect the differences in the stereochemistry of the heme pocket of the proteins brought about by different forms of chemical modification. Further studies are planned to verify this and to investigate the underlying molecular mechanism of desferrioxamine's action. Also planned is a follow up study in which a more powerful and effective family of iron chelating pyridinone compounds will be used.