Fedevych Y. Role of haptoglobin and haptoglobin-hemoglobin complex in the system of antioxidant defense under oxidative stress development in the experiment and in patients with lung cancer

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0409U005100

Applicant for

Specialization

  • 03.00.04 - Біохімія

12-10-2009

Specialized Academic Board

Д 26.001.24

Taras Shevchenko National University of Kyiv

Essay

The role of haptoglobin and haptoglobin-hemoglobin complex in the system of antioxidant defense in the experiment as well as in patients with lung cancer was investigated. It was revealed that haptoglobin-hemoglobin complex is characterized by lower nitrite-reductase activity while compared with extraerythrocytar hemoglobin. Activity of nitrite-reductase reaction with the hemoglobin at the 1 minute was higher, which is testified by E of this reaction which averaged 0.028 0.0037. Significantly lower speed of the reaction was revealed in the interaction of Hp-Hb complex - 0.018 0.0033. It was also investigated that haptoglobin-hemoglobin complex has higher peroxidase activity while compared with free hemoglobin and therefore prevents formation of surplus quantities of nitric oxide and possibly stores NO and prevent lipid peroxidation. It was revealed that haptoglobin-hemoglobin complex is characterized by lower nitrite-reductase activity while compared with extra-erythrocyte hemoglobin and higher peroxidase activity while compared with free hemoglobin Therefore, haptoglobin-hemoglobin complex prevents formation of surplus nitric oxide amounts and probably in this way storages nitric oxide and prevents initiation of lipid peroxidation processes. It was revealed that Hp-Hb complex in extra-erythrocyte space binds oxygen easier than free hemoglobin. It was demonstrated that exogenous introduction of L-arginine induces elevation of nitrite-anion content in blood plasma and erythrocytes of experimental animals, activates lipoperoxidation and glutathione-depended antioxidant defense, at the same time activities of catalase and NADH++H+-depended methemoglobinreductase decreased. Modeling of haemic hypoxia by the introduction of sodium nitrite to experimental animals increased of haptoglobin content in blood serum and revealed tendency to decrease of middle mass molecules. Under acute hypoxic hypoxia content of middle mass molecules increased and preceding introduction of carnosine prevented elevation of middle mass molecules concentration in blood. In patients with lung cancer of II-III stages elevation of haptoglobin concentrations in blood serum was observed. It was revealed that in patients with lung cancer of II-III stages before the operation concentration of this glycoprotein averaged 220.68 4.36 mg%, in postoperative period: on the 3d day after the operation - 310.68 3.49 mg%, 8th day - 306.12 1.12 mg%, on the 15th day - 267.02 1.23 mg%, 21st day - 190.04 1.32 mg%, correspondingly. It was revealed that haptoglobin has a membrane-protecting influence and protects erythrocytes from acid hemolysis in vitro. Addition of haptoglobin to the incubation medium (0.16 mg of erythrocyte suspension) increased time of hemolysis from 6.16 0.25 min to 7.08 0.20 min. Elevation of TBA-active lipoperoxidation products, nitric oxide derivatives, middle mass molecules content and activity of glutathione reductase were revealed in erythrocyte hemolysate in patients with lung cancer. Activities of glutathione peroxidase, catalase and NADH++H+-depended methemoglobinreductase decreased. In postoperative period tendency to the normalization of mentioned shifts was observed. Received data testify important role of haptoglobin in antioxidant status formation in the blood and whole organism.

Files

Similar theses