[Impact of summer heat waves on key parameters of oxidative stress in patients with coronary artery disease].

AIM: To assess the impact of summer heat waves on key parameters of oxidative stress in patients with coronary heart disease. MATERIALS AND METHODS: We included 30 male patients aged 5213 years with stable angina pectoris of IIIII functional class with at least one coronary artery stenosis proved by angiography (ischemic group) in comparison with 10 male patients aged 487 years with no angiographic sings of significant coronary stenosis and without angina manifestation (non-ischemic group). The following parameters were studied: activity of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), the level of malondialdehyde (MDA) and MDA-modified low-density lipoproteins (MDA-LDL). The analysis of indicators was performed at normal average daily temperature (daytime temperature not higher than 20С) and after a heat wave (daytime temperature above 27C for more than 2 consecutive days). RESULTS: Our study revealed the decrease of CAT and GSH-Px activities with increased activity of Cu,Zn-SOD in both groups after the heat wave. At the same time we observed accumulation of MDA and increased MDA-LDL level in both groups. Initially ischemic patients showed significantly increased level of CAT and GSH-Px activity compared to the non-ischemic group, while it was no difference in activity of Cu,Zn-SOD and MDA and MDA-LDL level. We observed significant reduce of Cu,Zn-SOD activity in ischemic patients compared to non-ischemic group with no significant differences in all other studied parameters of oxidative stress after heat wave. CONCLUSION: Changes in the key parameters of oxidative stress in patients with ischemic heart disease during summer heat waves are comparable to those in patients without ischemia, however significantly greater inhibition of GSH-Px activity and significantly lower increase in Cu,Zn-SOD activity was noted. These results may indicate misregulation of free radical processes in patients with ischemic heart decease.

Oxidative and carbonyl stress as a factors of the modification of proteins and DNA destruction in diabetes.

AIM: To study the oxidative damage of biopolymers (proteins and nucleic acids) in blood of patients with type 2 diabetes mellitus (DM). MATERIALS AND METHODS: In the blood of 50 patients with DM and 25 patients without disorders of carbohydrate metabolism were estimated: the level of oxidized low-density lipoprotein (oxLDL) by immunochemical method, the content of SH-groups in plasma proteins, the activity of Cu, Zn-superoxide dismutase (SOD) in erythrocytes, the length of telomere in leukocyte DNA, the level of 8-hydroxy-2'-deoxygunosine (8-oxo-dG) in plasma and urine. RESULTS: It is shown that in DM patients the level of oxLDL increases and the content of SH-groups in proteins and peptides of the blood plasma decreases, which indicates the development of oxidative stress. In addition, a carbonyl-dependent modification of erythrocyte SOD was detected in DM patients, as well as oxidative DNA destruction (decrease in telomere length in leukocytes and an increase in the level of 8-oxo-dG in blood plasma and urine). CONCLUSION: On the basis of the definition of a complex of correct indicators, a multiple oxidative modification of biopolymers of blood (proteins and DNA) was detected in patients with DM.

Methylglyoxal as a scavenger for superoxide anion-radical.

Methylglyoxal at a concentration of 5 mM caused a significant inhibition of superoxide anion radical (O2 (·-)) comparable to the effect of Tirone. In the process of O2 (·-) generation in the system of egg phosphatidylcholine liposome peroxidation induced by the azo-initiator AIBN, a marked inhibition of chemiluminescence in the presence of 100 mM methylglyoxal was found. At the same time, methylglyoxal did not inhibit free radical peroxidation of low-density lipoprotein particles, which indicates the absence of interaction with methylglyoxal alkoxyl and peroxyl polyenoic lipid radicals. These findings deepen information about the role of methylglyoxal in the regulation of free radical processes.

Antioxidant Action of Apelin-12 Peptide and Its Structural Analog In Vitro.

The effects of C-terminal fragment of natural peptide apelin-12 H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH (A12) and its structural analog H-(N(α)Me)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH (AI) on Cu(2+)-induced free radical oxidation of low-density lipoprotein in human blood plasma and activity of commercially available enzymes superoxide dismutase and catalase in a concentration range of 0.01-1 mM were examined. A12 and AI had no effect on superoxide dismutase and catalase activities during 24-h co-incubation with these enzymes at 4°C. When used in a concentration of 1 mM, A12 and AI decreased the maximum low-density lipoprotein oxidation rate by 51 and 47%, respectively, and lengthened the lag phase of low-density lipoprotein oxidation by 2.6 and 1.8 times, respectively, which confirmed their antioxidant potency.

Fructose as an inducer of free radical peroxidation of natural lipid-protein supramolecular complexes.

D-fructose strongly stimulates peroxidation of natural lipid-protein supramolecular complexes in vitro regardless of the oxidation initiation method. Fructose (ketose) intensifies free radical peroxidation to a much greater extent than glucose (aldose), which is important for the etiology and pathogenesis of diabetes mellitus.

[Impact of a cold wave on disease course, hemodynamics, carbohydrate metabolism, and blood rheological properties in cardiac patents].

AIM: To study the impact of cold waves on disease course, hemodynamics, lipid and carbohydrate metabolisms, oxidative stress, and blood rheological properties in patients with cardiovascular diseases (CVD). SUBJECTS AND METHODS: 24 men and 36 women (their mean age was 62.9±9.7 years) were examined; coronary heart disease (CHD) and hypertension were present in 40 and 95% of the patients, respectively; selected therapy remained unchanged throughout the entire period. The investigators measured blood pressure and pulse wave velocity (PWV), carried out biochemical blood tests, estimated plasma oxidized low-density lipoproteins (oxLDL) and malondialdehyde (MDA) and erythrocyte superoxide dismutase (SOD) activity, calculated a MDA/SOD ratio, determined blood viscosity; as well as assessed quality of life using a visual analogue scale (VAS) and a specially developed questionnaire. RESULTS: Female sex, CHD, type 2 diabetes mellitus (DM-2) were independent predictors of cardiovascular events (CVEs) in the frost period. The persons who had experienced CVEs in frost had higher baseline PWV. CVEs, such as hypertensive crisis, emergency calls, cardiac arrhythmias, and the larger number of adverse reactions, were more commonly recorded in frost. There was an increase in blood glucose levels, a decrease in oxLDL, a rise in η2/η1, and a reduction in plasma viscosity during frost and elevated glycation end product levels at visit 2. Conclusion. The cold wave is associated with the larger number of CVEs in some patients with CVD during selected therapy. CHD, DM-2, female sex are independent predictors of CVE in patients with CVD during the winter period. In this period, there were increases in the levels of glucose, glycation end products, and erythrocyte aggregation, and a reduction in plasma viscosity.

Apelin-12 and its structural analog enhance antioxidant defense in experimental myocardial ischemia and reperfusion.

This study investigated the effects of peptide apelin-12 (H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH, A12) and its novel structural analog (H-(N(α)Me)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, AI) on myocardial antioxidant enzyme activities, lipid peroxidation, and reactive oxygen species formation in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury. Isolated working rat hearts were subjected to global ischemia and reperfusion. Infusion of 140 µM A12 or AI before global ischemia improved cardiac function recovery; increased the activity of Cu,Zn superoxide dismutase (Cu,Zn SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); decreased malondialdehyde (MDA) content in reperfused heart; and reduced the formation of hydroxyl radical adduct of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide in the myocardial effluent during early reperfusion compared with these indices in control. Anesthetized open-chest rats were subjected to the left anterior descending coronary artery occlusion and coronary reperfusion. Peptide A12 or its analog AI was injected intravenously at the onset of reperfusion at a dose of 0.35 µmol/kg. Treatment with A12 or AI significantly limited infarct size and reduced the activity of lactate dehydrogenase and creatine kinase MB isoenzyme in blood plasma at the end of reperfusion compared with control. These effects were accompanied by complete recovery of Cu,Zn SOD, CAT, and GSH-Px activities; and decrease in MDA content in the area at risk by the end of reperfusion. The study concluded that C-terminal fragment of native peptide apelin-12 and its synthesized analog is involved in the upregulation of cardiac antioxidant defense systems and attenuation of lipid peroxidation in myocardial I/R injury.

[Antioxidant properties of apelin-12 and its structural analogue in experimental ischemia and reperfusion].

Effects of apelin-12 H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH (A12) and its modified analogue H-(NMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH (I) on activity of antioxidant enzymes, formation of malonic dialdehyde (MDA) and generation of reactive oxygen species (ROS) were studied in ex vivo and in vivo models of myocardial ischemia and reperfusion (I/R) injury in Wistar rats. Preischemic infusion of peptide A12 or AI enhanced cardiac function recovery of isolated perfused heart and was accompanied by a marked attenuation of ROS generation detected by electron paramagnetic resonance (EPR) technique in myocardial effluent at early reperfusion compared with control. Intravenous administration (i.v.) of peptides in narcotized rats with regional myocardial ischemia limited infarct size and reduced activity of lactate dehydrogenase and MB-fraction of creatine kinase in plasma at the end of reperfusion. Treatment with peptide A12 prevented reduction or augmented activity of myocardial u/Zn superoxide dismutase, catalase and glutathione peroxidase by the end of reperfusion in both I/R models compared with control. Increased MDA content in the area at risk of rat heart in situ at the end of reperfusion was reduced to the initial value under the effect of i.v. A12 administration. Therefore, cardioprotective action of natural apelin-12 and its structural analog AI involve reduction of short-lived ROS generation and improvement of the antioxidant state of ischemic heart during reperfusion.

[The role of oxidative processes in augmentation of atherogenity of low density lipoprotein particles].

We investigated action of natural dicarbonyl compounds which are formed in atherosclerosis and diabetes on properties of low density lipoproteins (LDL) such as surface charge, conformational changes of apoB100, susceptibility to oxidation. and aggregation rate. It was found that malonic dialdehyde (MDA) compared with glyoxal and methylglyoxal is more effective modificating agent of protein part of LDL particle. Nevertheless glyoxal and methylglyoxal-dependent modification of LDL can accelerate processes of further free radical peroxidation increasing atherogenity of LDL particles.

[The anti-ischemic and antioxidant activity of the pharmacological agonist of galanin receptor GalR2 and carnosine in in vitro and in vivo model systems]. / Protivoishemicheskaia i antioksidantnaia aktivnost' farmakologicheskogo agonista retseptora galanina GalR2 i karnozina v model'nykh sistemakh in vitro i in vivo.

Antioxidant and anti-ischemic properties of the pharmacological agonist of galanin receptor GalR2 WTLNSAGYLLGPßAH (Gal) and its C-terminal fragment, dipeptide carnosine (ßAH), were studied in the model of regional ischemia and reperfusion of the rat heart in vivo in the dose range of 0.5-5.0 mg/kg and Cu²âº-induced free radical oxidation of low density lipoproteins (LDL) of human plasma in vitro for peptide concentrations of 0.01 mM and 0.1 mM. Gal was obtained by automatic solid phase synthesis using the Fmoc methodology; its structure was characterized by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Intravenous administration of the optimal dose of Gal (1 mg/kg) to rats after ischemia was more effective than carnosine in reducing of the myocardial infarct size and the activity of creatine kinase-MB and lactate dehydrogenase in blood plasma at the end of reperfusion. It also improved the metabolic state of the reperfused myocardium and reduced the formation of peroxidation products during reperfusion. Gal reduced more effectively the formation of adducts of hydroxyl radicals in the interstitium of the area at risk (AAR) of the rat heart than carnosine. Carnosine at a dose of 1 mg/kg more effectively increased the activity of catalase and glutathione peroxidase in the AAR by the end of reperfusion compared to Gal. In a model of Cu²âº-initiated oxidation of human plasma LDL 0.1 mM carnosine demonstrated a significantly more pronounced reduction in the formation of lipid radicals compared to Gal. The results show that Gal can be considered as a promising agent that reduces myocardial injury during reperfusion and oxidative stress.

Interrelation between malonyl dialdehyde-dependent modification and cholesterol content in low-density lipoproteins.

Epidemiological study of an independent representative sample of population revealed a strong positive correlation between the content of oxidized (MDA-modified) LDL and concentration of atherosclerosis biomarkers (total cholesterol and LDL cholesterol) in blood plasma from 348 probands. The correlation between these parameters was more significant in atherosclerotic patients, but was less pronounced in probands with diabetes mellitus. The correlation between the concentration of atherosclerosis markers and content of MDA was absent in probands with diabetes mellitus. These data attest to the presence of LDL-modifying agents differing from MDA (e.g., glyoxal and methylglyoxal) in the blood of diabetes mellitus patients. We conclude that the content of MDA-modified LDL can serve as an additional biomarker of atherosclerosis.

[Acute and postponed action of adriamycin on the contractile function and antioxidant status of the myocardium].

Functional, biochemical and morphological studies of rat cardiac muscle after single injection of adriamycin (2.2 mg/kg) were carried out. The myocardium was taken for studies in 2 hours and in 2-3 weeks after adriamycin injection. The isolated heart was perfused retrogradely with Krebs solution and left ventricular isovolumic pressure and perfusion pressure were continuously monitored. Two-fold increase in perfusion rate was accompanied by raised developed pressure, heart rate and perfusion pressure which in the given conditions reflected a tone of coronary vessels. The cardiac contractile function of rats that received adriamycin 2 hours before, remained unaltered as compared to control group, however, perfusion pressure was raised by 26%. These hearts responded to H2O2 introduction (100 microM) into coronary vessels by more profound fall in developed pressure, which fell to 31 +/- 8% after 40 minutes vs. 61 +/- 5% in the control group (p<0.01). In two-three weeks after adriamycin injection, both cardiac contractile function and its responsiveness to oxidative stress induced by H2O2 introduction did not differ from the control, however, perfusion pressure remained elevated and this was accompanied by slowed myocardial relaxation. The myocardial concentration of malonic dialdehyde was moderately increased in adriamycin-treated group in both terms while the activity of antioxidant enzymes (SOD, GPHx and catalase) remained unaltered. Results showed an absence of the direct connection between myocardial antioxidant status and the contractile function changes at adriamycin action.

The Mechanisms of Cardiac Protection Using a Synthetic Agonist of Galanin Receptors during Chronic Administration of Doxorubicin.

The use of the anticancer drug doxorubicin (Dox) is limited by its cardiotoxic effect. The aim of this work was to study the effect of a new synthetic agonist of the galanin receptor GalR1-3 [ßAla14, His15]-galanine (2-15) (G) on the metabolism, antioxidant enzyme activity, and cardiac function in rats with cardiomyopathy (CM) caused by chronic administration of Dox. Coadministration of peptide G and Dox significantly increased the fractional shortening (FS) and ejection fraction (EF) by an average of 30 ± 4% compared with the indices in the Dox group. The reduced severity of cardiac dysfunction under the action of G was accompanied by a 2.5-fold decrease in the activity of creatine kinase-MB (CK-MB) in blood plasma. The protective mechanism of the action of peptide G is caused by a reduced lipid peroxidation (LP) that is due to the increased activity of Cu,Zn superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GSH-Px) in the damaged heart. Administration of peptide G significantly increased the adenine nucleotide pool (ΣAH), ATP content, and the levels of phosphocreatine (PCr) and total creatine (ΣCr) in the damaged myocardium. It also reduced lactate accumulation relative to its content in the Dox group. The better energy supply of cardiomyocytes after treatment with peptide G prevented the accumulation of cytotoxic ammonia and disruption in the metabolism of the key myocardial amino acids (glutamic acid (Glu), aspartic acid (Asp), and alanine (Ala)). Peptide G significantly improved the morphological parameters of the heart in rats treated with Dox. The results show promise in using peptide G to efficiently correct functional, morphological, and metabolic damage to the heart caused by anthracycline chemotherapy.

[Effect of ubiquinone on contractile function and antioxidant status of the myocardium in spontaneously hypertensive rats].

During the period of aging of spontaneously hypertensive rats (SHR) between 6 and 13 weeks the systolic arterial pressure increased from 131+/-2 up to 176+/-3 mm Hg while in the control group of WKY rats it reached 122+/-2 mmHg. The hypertension was combined with myocardial hypertrophy -- the relative weight of SHR heart was 24% higher. The contractile myocardial function of the isolated isovolumic heart of SHR group did not differ from WKY group in a wide range of coronary perfusion rates. During oxidative stress induced by 40-min intracoronary introduction of H(2)O(2) function of hypertrophied SHR hearts fell significantly deeper. This coincided with decreased myocardial activity of superoxide dismutase and glutathione peroxidase by 29-30%, and increased catalase activity by 18%. The rate of generation of active forms of oxygen (hydroxyl radicals HO(.-)) in mitochondria from SHR hearts was higher as compared with WKY. Thus, the development of hypertension was combined with decreased antioxidant protection of the myocardium. The addition of ubiquinone to drinking water (approximately 10 mg/kg/day) for 6 weeks did not affect arterial pressure level, but was associated with two times lesser degree of myocardial hypertrophy. The hearts of SHR that received ubiquinone differed from those not treated with ubiquinone by increased maximal level of myocardial contractile function, and by improved myocardial relaxability and distensibility. After administration of H(2)O(2), myocardial function of SHR was kept on higher level. That was combined with less myocardial oedema, better preservation of antioxidant enzymes and reduced rate of succinate-dependent generation of superoxide radicals in mitochondria from hearts of ubiquinone treated SHR. The results have shown, that administration of ubiquinone to rats with hereditary hypertension reduces degree of myocardial hypertrophy, improves functional properties of the myocardium, promotes effective protection of antioxidant enzymes and increases the resistance of the cardiac muscle to oxidative stress.

[Primary pulmonary hypertension: activation of sympathico-adrenal system and free radical oxidation. Positive effects of carvedilol therapy].

AIM: To study the condition of the sympathico-adrenal system (SAS), synthesis of cAMP dependent on beta2-adrenoreceptors and parameters of free radical oxidation in patients with primary pulmonary hypertension (PPH); to examine efficacy of non-selective beta- and alpha1-adrenoblocker carvedilol in PPH patients. MATERIAL AND METHODS: Twenty patients with PPH had 6-minute walk test, ECG monitoring with assessment of heart rhythm variability (HRV). Tests for noradrenalin and adrenalin concentration in blood plasma, cAMP synthesis by blood lymphocytes in basal conditions and under stimulation with isoproterenol and forskolin, free radical oxidation were made initially, 1 and 6 months later. Ten patients received carvedilol in addition to standard therapy, 10 patients served control. RESULTS: PPH patients had higher NA in the blood, low cAMP synthesis, high malonic aldehyde, low activity of glutathionperoxidase, increased activity of superoxidedismutase and catalase of erythrocytes. The most pronounced changes in the above parameters were observed in patients with PPH FC III-IV. HRV declined in progression of cardiac failure. 6-months of combined treatment with carvedilol increased the distance of 6-min walk. Carvedilol had no effect on HRV, it reduced NA, stimulated cAMP synthesis, demonstrated no antioxidant activity. CONCLUSION: In PPH there is activation of SAS and desensitization of beta2-AR cells, oxidative stress develops. Addition of carvedilol to standard therapy with PPH improves clinical condition due to adrenoblocking properties of the drug.

[The role of free radical inhibitors of lipid peroxidation in protecting the myocardium from ischemic damage]. / Rol' ingibitorov svobodnoradikal'nogo perekisnogo okisleniia lipidov v zashchite miokarda ot ishemicheskogo povrezhdeniia.

The natural antioxidant beta-carotene which, unlike phenol antioxidants such as dibunol and SPN-6, is capable of exhibiting antioxidative properties under low partial oxygen pressure (ischemia), has been found to increase the activity of antioxidative enzymes in the intact and infarct myocardium and to greatly exert a more antinecrotic action when given orally in a dose of 20 mg/kg in models of rat coronary-occlusion myocardial infarction than the phenol antioxidants mentioned above. Intravenous administration of copper-containing enzymes utilizing O2 superoxide dismutase (SOD), 4 mg/kg, or ceruloplasmin, 50 mg/kg, as with a highly disperse copper powder promoting a substantial increase in antioxidative enzyme activity in the rat myocardium has been demonstrated to reduce the zone of myocardial ischemic lesion in rats and to largely enhance postoperative survival rates in the animals. Three hours following intravenous SOD, an electron microscopic examination of rat ischemic myocardium showed a considerable fall in the structural and functional damages to cardiomyocytes in the periischemic area. The findings suggest that free radical processes make a contribution to ischemic cardiomyocyte lesion and open the way for pharmacological therapy of postischemic abnormalities with enzymatic and non-enzymatic preparations of antioxidants.

[Changes in the activity of antioxidant enzymes in patients with hypertension]. / Izmenenie aktivnosti antioksidantnykh fermentov u bol'nykh gipertonicheskoi bolezn'iu.

The authors examined the activity of the antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GP) in the blood of patients with permanent essential hypertension and hypertensive crises and changes in the activity of these enzymes when monotherapy with the calcium antagonist corinfar was used. A total of 62 patients (age 52.7 +/- 0.7 years) with hypertension and 25 apparently healthy volunteers (age 43.9 +/- 0.7 years) were examined. The activity of SOD and GP was found to be decreased by 33 and 22%, respectively, in patients with permanent hypertension and by 40 and 32%, respectively, during hypertensive crises. When hypertension was treated with corinfar, the activity of COD and GP was increased by 10 and 18%, respectively. Concurrently, these patients had subjective and clinical improvement. The findings suggest that impaired lipid peroxidation makes a great contribution to the pathogenesis of essential hypertension. It can be assumed that the use of antihypertensive agents producing effects on the level of lipid peroxidation products and the enhancements of the activity of antioxidative enzymes.

[Alterations of the aortic endothelium ultrastructure after the administration of cholesterol oxidation products to rabbits]. / Izmenenie ul'trastruktury éndoteliia aorty pri vvedenii krolikam produktov okisleniia kholesterina.

Intravenous administration of 7 alpha-hydroxycholesterol and cholestane-triol at the dose of 2.5 mg/kg produces, one day later, ultrastructural alteration of aortic endothelial cells such as cytoplasmic vacuolation, protruding and crateriform surface defects, subendothelial oedema with a subsequent exfoliation of endotheliocytes. The endothelial damage was more pronounced after the administration of equal doses of cholestane-triol as compared to 7 alpha-hydroxycholesterol. Ultrastructural changes 10 days after oral administration of 500 mg/kg cholesterol mixed with its auto-oxidation products were similar to those developing after cholestane-triol and 7 alpha-hydroxycholesterol. Cholesterol free of the oxidation products at the same doses did not produce alterations in the rabbit aortic endothelium.

[Hyperbaric oxygenation and antianginal agents: effects on blood levels of malondialdehyde and activities of antioxidative enzymes in patients with ischemic heart disease]. / Giperbaricheskaia oksigenatsiia i antianginal'nye preparaty: vliianie na soderzhanie malonovogo dial'degida i aktivnost' antioksidantnykh fermentov krovi u bol'nykh ishemicheskoi bolezn'iu serdtsa.

The time course of serum levels of malonic dialdehyde and red blood cell activity of antioxidative enzymes, such as superoxide dismutase and glutathione peroxidase, was assessed from the outcomes of hyperbaric oxygenation combined with antianginal therapy in 38 patients with functional classes II-III stable angina on effort without clinical manifestations of circulatory failure. Hyperbaric oxygenation involved 10-12 sessions at 1.5 ata during 40 min each. The antianginal agents (long-acting nitrates, beta-adrenoblockers, nifedipine) were given in median therapeutical doses. The control group included 26 patients who had hyperbaric oxygenation in the same fashion without taking antianginal drugs. The criteria for beneficial therapy were a reduction in the number of anginal episodes and the nitroglycerin tablets used, an increase in exercise tolerance, as evidenced by repeated bicycle ergometric test. The positive clinical effect of a hyperbaric oxygenation course was shown to be accompanied by higher activity of superoxide dismutase in the red blood cells. The use of nifedipine in the multimodality anginal therapy prevents the hyperbaric oxygenation-induced increase in serum malonic dialdehyde levels.

[The modification of Cu, Zn-superoxide dismutase by monomethoxypolyethylene glycol improves the indices of the experimental therapy of the ischemic myocardium in rats]. / Modifikatsiia Cu, Zn-superoksiddismutazy monometoksipoliétilenglikolem uluchshaet pokazateli ékpserimental'noi terapii ishemizirovannogo miokarda krys.

Mice were used to make a comparative study of the biological distribution of intravenous preparations of native and monomethoxypolyethylene glycol-modified superoxide dismutase isolated from bovine liver, as well as native and aldehyde dextran. The study demonstrated that the biodistribution of the native enzymes from various sources was, however, equal, but in the mouse liver there was a higher accumulation of SOD isolated from the rat liver. AD-SOD was found to have a longer half-life in the blood and in the liver of mice, in particular, while MPEG-SOD showed 10, 15, and 16 times longer in the lungs, blood and heart of the animals examined, respectively. The elevated accumulation of MPEG-SOD in some organs was used for their treatment, particularly for experimental therapy of rat myocardial ischemia. A rat model of ischemia demonstrated that the intravenous bolus administration of MPEG-SOD reduced the size of a myocardial necrotic area by 40% as compared to a 13% decrease when the other compounds were assayed. The findings suggest that the MPEG-SOD preparation is promising for decreasing reperfusion injuries of the cardiovascular system and the lungs.