Effect of hyperhomocysteinemia on erythrocyte function and its impact on erythropoiesis in experimental rats

ABSTRACT

The current work was conducted to study the possible effect of hyperhomocysteinemia [HHcy] on some erythrocytic functions as a cause of anemia and its impact on erythropoietin [EPO] release in experimental rats. Forty adult male albino rats were divided into two main groups, the control group [Group I] and the hyperhomocysteinemic group [HHcy] [Group II]. Hyperhomocysteinemia was induced by subcutaneous injection of DL- homocysteine at a dose of 100 mg/kg/day for 4 weeks. At the end of the fourth week each main group was subdivided into two subgroups, [Ia] control, [Ib] Hypoxic-control [IIa] and HHcy, [IIb] Hypoxic-HHcy. Hypoxia was induced by a single intra-peritoneal injection of desferrioxamine [200 mg/kg] 22 hours before decapitation. Whole blood was used for determination of erythrocytic fragility, hematological parameters, reticulocyte percentage. Homocysteine, erythropoietin [EPO], urea and creatinine were estimated in plasma. Erythrocytes were used for estimation of lipid peroxidation, G6PDH activity and membrane separation for deten-nination of Na[+] K[+] ATPase enzymatic activity. Homocysteine, EPO and creatinine plasma levels, and reticulocyte% and erythrocytic lysis in addition to erythrocyte lipid peroxidation were all significantly higher, while G6PDH and Na[+] K[+]- ATPase enzymatic activities were significantly lower in the HHcy group as compared to the control group. A significant positive correlation was found between total Hcy plasma levels and erythrocyte lipid peroxidation. EPO plasma levels showed a significant increase in response to hypoxic stimulation in the control group, while blunted response was observed in the HHcy group. It could be concluded that disturbance in erythrocyte membrane and enzymatic functions in HHcy increases the susceptibility of RBCs to hemolysis and reduces its life span. Hyperhomocysteinemia also impacts EPO release to hypoxic stimulation which may be due to damaging effect of HHcy on renal cells