Antioxidant defense and trace element imbalance in patients with postradiation syndrome: first report on phase I studies.

More than 6000 residents of Latvia were involved in recovery work in Chernobyl. They were healthy men exposed to substantial ionizing radiation (0.01-0.5 Gy). Now, these recovery workers suffer from "postradiation syndrome": dizziness and poor memory, headache, local pains, and so forth. The biochemical mechanism of "postradiation syndrome" has not been completely established. In this Phase I study, we have investigated how exposure to radiation impacts antioxidative defense and trace element concentrations in the blood of recovery workers. Thirty-five patients with postradiation syndrome (men, age range 33-50 yr) and 15 healthy men similar in age as control subjects were studied for the effects on plasma chemiluminescence, the activity of antioxidant enzymes, and the concentration of ceruloplasmin and concentrations of selenium (Se), zinc (Zn), and copper (Cu) in blood. The results revealed that plasma chemiluminescence was significantly increased (3.5-fold to 5.5-fold), the activity of catalase in erythrocytes was significantly elevated, and the activity of glutathione peroxidase in plasma was significantly reduced in examined patients. Concentrations of Zn and Cu were significantly higher and the concentration of Se was lower in these patients. We conclude that the patients exposed to ionizing radiation have diminished blood antioxidant defense associated with pronounced Se deficiency and imbalance of Zn and Cu.

Anaemia and antioxidant defence of the red blood cells.

Antioxidant defence was investigated in red blood cells (RBC) in 56 patients with 3 different haemoblastoses: polycythemia vera (PV), chronic myelogenous leukaemia (CML), chronic lymphoid leukemia (CLL) with and without anaemia, in 12 iron deficiency anaemia (A) patients and 50 healthy persons. The activities were determined of the following antioxidant enzymes: glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT) and MDA levels. Antioxidant defence is decreased and the level of lipid peroxidation are increased in RBC in all patients (PV, CML, CLL, A). Different changes were detected in the antioxidative defence between normal red blood cells and those formed from leukaemic cells clone. In normal RBC in anaemia (CLL, A) opposite deviation of G6PD and GSSG-R activities was observed. In RBC formed from leukaemic cell clone (PV, CML), a simultaneous significant increase in G6PD and GSSG-R activities was found, which indicated activisation of pentose phosphate pathways (PPP) in these pathologies; in anaemia they function less effectively.

[The effect of treatment with superoxide dismutase and selenium on blood ferritin and transferrin level in patients with hemoblastosis]. / Vliianie terapii superoksiddismutazol i selenom na uroven' ferritina i transferrina v krovi bol'nykh gemoblastozami.

The effect of superoxide dismutase (SOD) and selenium on the blood level of ferritin and transferrin in patients with hemoblastosis was studied. Two-month treatment with SOD and selenium had no effect on the level of ferritin but reduced the concentration of malonic dialdehyde (MDA) in the native erythrocytes in patients with chronic lymphoid leukemia practically to that in healthy individuals. In erythrocytes which formed from cells of the leukemic clone (chronic myelocytic leukemia and erythremia) treatment with SOD and selenium reduced the pathologically high level of ferritin, but at the same time increased the concentration of MDA in the erythrocytes. In erythremia in the group with a low level of ferritin SOD and selenium caused no statistically significant increase in its level in blood.

[Erythremia: the activity of erythrocyte antioxidant enzymes and the association with iron deficiency]. / Eritremiia: aktivnost' antioksidantnykh fermentov éritrotsitov, sviaz' s defitsitom zheleza.

Concentration of malonic dialdehyde (MDA) and activity of antioxidant enzymes G-6-PD, glutation peroxidase (GP), glutation reductase, catalase, superoxide dismutase were measured in red cells of patients with polycythemia vera. Plasmic ions Fe3+ were estimated by means of electron-paramagnetic resonance. MDA concentration and antioxidant enzymes (except GP) in polycythemia red cells were found increased, while the activity of selenium-dependent GP was reduced, the inhibition being greatest in severe iron deficiency. It is suggested that GP activity in red cells depends on both selenium levels in the body and concentrations of non-hematic iron.

[Possible use of erythrocyte antioxidant enzymes as markers of the course of disease in patients with hemoblastoses]. / Vozmozhnost' ispol'zovaniia antioksidantnykh fermentov éritrotsitov v kachestve indikatorov, kharakterizuiushchikh techenie bolezni u bol'nykh gemoblastozami.

Blood and erythrocytes of 50 healthy volunteers and 105 patients with different forms of hemoblastoses were investigated. 54 patients had acute phase, 51 patients--remission stage of disease. Essential differences in the activity of antioxidant enzymes (SOD, CAT, GSH-Px) were detected and compared with content of MDA and degree of anaemia. Acute phase had more significantly alteration of antioxidant defence: diverse changes of the activity of SOD and CAT, significantly inhibition of GSH-Px, the high level of MDA and increased degree of anaemia.

The activity of glucose-6-phosphate dehydroxygenase and glutathione enzymes in red blood cells in patients with haemoblastoses.

The activity of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px) and MDA levels have been assayed in red blood cells (RBC), obtained from 57 people suffering from haemoblastoses. The activities of G6PD in the RBC in patients with polycythemia vera (PV) and chronic lymphoid leukemia (CML) are significantly higher than those in healthy patients. Changes in the activity of glutathione dependent enzymes GSSG-R and those of GSH-Px in the RBC go in opposite directions: the activity of GSSG-R is significantly enhanced in patients with PV and CML, but the activity of GSH-Px is decreased in all patients suffering from haemoblastoses. The high levels of MDA in the RBC of all patients with haemoblastoses indicate intensification of lipid peroxidation in their RBC.

[Study of pantothenic acid derivatives as cardiac protectors in a model of experimental ischemia and reperfusion of the isolated heart]. / Izuchenie proizvodnykh pantotenovoi kisloty v kachestve kardioprotektorov na modeli éksperimental'noi ishemii i reperfuzii izolirovannogo serdtsa.

An isolated heart model with experimental ischemia and reperfusion was used to show effective decrease in lactate, increase in ATP content and prevention of conjugated dienes accumulation in the myocardium by derivatives of pantothenic acid: panthenol (9.0 mg/kg), calcium pantothenate (15.6 mg/kg) and by these ones applied simultaneously as ingredients of perfusate (25 microM) in postischemic period. In that way derivatives of pantothenic acid should be regarded as cardiac protectors.

[Effect of pantethine on post-heparin lipolytic activity and lipid peroxidation in the myocardium]. / Vliianie pantetina na postgeparinovuiu lipoliticheskuiu aktivnost' i perekisnoe okisleniie lipidov v miokarde.

In the present work the effect of the precursor of Co a D-bis (N- pantothenyl-beta-aminoethyl) disulfide--pantethine on post heparin lipolytic activity and the intensity of lipid peroxidation has been investigated. Pantethine in doses of 5 mg/kg enhanced post heparin lipolytic activity (60.6%) and lipoprotein lipase activity (39.9%) in plasma and reduced the amount of NEFA (35.1%) and content of MDA (57.4%) in the mitochondria.