Blood labile iron effect on nitrosative stress development under rat experimental rhabdomyolysis

Under experimental model of glycerol-induced rhabdomyolysis in rats new pool of nonheme iron formation in the blood plasma and it’s effect on NO synthesis was stu­died. On the first day after intramuscular 50% glycerol injection (10 ml/kg) more than 10 times increase of free heme content in plasma and 6 times increase of heme oxygenase activity in the liver was registered. Labile ferric iron pool formation in rhabdomyolysis rat blood plasma, which is completely absent in the samples of the intact group, was proved by EPR analysis. In period from 1st to 6th day of the experiment the contents of this form of iron was greater than 2 mg/L. It is significantly higher than the concentration of transferrin associated iron. During blood labile iron pool formation, an increase of nitrosative stress indicators was observed. On the 4th day, total NO synthase concentration in the liver, as well as S-nitrosothiols and nitrosoprolin in plasma, was 2 times higher than in control. To test the hypothesis about labile iron involvement in nitrosative stress development iron acceptor – unithiol was applied. Unithiol application led to 3 time decrease in blood plasma labile iron concentration on the 4th day of pathology in comparison with animals with experimental rhabdomyolysis. Positive correlation between blood labile iron concentration and nitrosative stress indicators was detected: total NO synthase, nitrosoprolin and S-nitrosothiols concentrations decreased by 1.5 times after blood labile iron concentration lowering. Under glycerol-stimulated rhabdomyolysis development in rat, new pool of nonheme ferric iron is formed in plasma. It is not included in transferrin and therefore is capable for chemical interactions. So we can conclude that labile iron is one of nitrosative stress initiators under rhabdomyolysis.