[The effect of 3,5-dicarbomethoxyphenylbiguanide on the activity of antioxidant enzymes].

The effect of 3,5-dicarbomethoxyphenylbiguanide, which was selected with the Prediction of Activity Spectra of Substances (PASS) computer program, on the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase in the heart and the blood serum of rats with experimental rheumatoid arthritis was investigated. The studied parameters changed towards control values when the tested compound was injected in animals with the pathology. These results can be explained by the cardioprotective and antioxidant activity of the compound. The data obtained during the study may be used for the development of new preventive and therapeutic agents for the treatment of the rheumatoid arthritis.

Influence of 10-(6'-Plastoquinonyl)decyltriphenylphosphonium (SkQ1) on Oxidative Status in Rats with Protamine Sulfate-Induced Hyperglycemia.

An influence of 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on oxidative status and activity of some antioxidant enzymes in the liver and blood serum from rats was examined during experimental hyperglycemia developed after injecting protamine sulfate. It was found that SkQ1 lowered glycemic level in rats treated with protamine sulfate. Moreover, it was also accompanied by restoration of the normal range of biochemiluminescence parameters indicating the rate of ongoing free radical processes, magnitude of primary products of lipid peroxidation such as diene conjugates, activity of aconitate hydratase, and level of citrate in rat liver and blood. Hence, it was demonstrated that activity of superoxide dismutase and catalase, increasing during hyperglycemia, was decreased after administering SkQ1. This might be related to the ability of SkQ1 to normalize free-radical homeostasis imbalanced during hyperglycemia.

Effect of SkQ1 on Activity of the Glutathione System and NADPH-Generating Enzymes in an Experimental Model of Hyperglycemia.

We studied the effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on the antioxidant activity of the glutathione system and NADPH-generating enzymes in liver and blood serum of rats with hyperglycemia induced by protamine sulfate. It was found that intraperitoneal injection of SkQ1 prevented both decrease in reduced glutathione level and increase in activity of glutathione system enzymes--glutathione peroxidase, glutathione reductase, and glutathione transferase. Activity of NADPH-generating enzymes--glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase--was also attenuated by SkQ1. Probably, in this model of hyperglycemia, decreased level of reactive oxygen species in mitochondria led to the decreased burden on the glutathione antioxidant system and NADPH-generating enzymes. Thus, SkQ1 appears to be a promising compound for the treatment and/or prevention of the adverse effects of hyperglycemia.

[Effect of melaxen on free radical processes intensity and some antioxidant enzymes activity in rats liver and blood serum under type 2 diabetes mellitus].

The effect of melaxen on free radical processes and activity of superoxide dismutase and catalase in rats with type 2 diabetes mellitus (T2DM) has been investigated. It was established that melaxen administration to diabetic rats caused a decrease of the intensity of free radical processes as evidenced a decrease of the lipid peroxidation primary products content and biochemiluminescence parameters. The activity of the antioxidant enzymes changed towards normal values. These effects were probably induced by the correction of the melatonin level at the result of the melaxen action.

[Intensity of apoptotic processes, aconitate hydratase activity and citrate level in patients with type 2 diabetes mellitus complicated steatohepatitis under application of epifamin at basic therapy].

DNA fragmentation, caspase-1 and caspase-3, aconitate hydratase (AH) activities, and citrate content have been investigated in the blood of patients with type 2 diabetes mellitus complicated by steatohepatitis. These indicators of apoptotic processes intensity and oxidative stress development were estimated after basic treatment and a combined therapy including epifamin. Before treatment DNA fragmentation blood leukocytes, decrease of AH activity and increase of caspases activities in the serum of patients were detected. Treatment with epifamin provided more pronounced changes in the investigated parameters towards control values as compared to basis therapy. Epifamin caused a positive effect on the citrate content in the serum of patients. Epifamin inclusion to the basic therapy was accompanied by a more pronounced changes towards the normal values of such biochemical parameters as ALT, AST, b-lipoproteins, cholesterol, fasting glucose and postprandial glucose levels. All these changes may be obviously attributed to epifamin-induced correction of the melatonin level and manifestation of adaptogenic properties and antioxidant effects of the hormone.

[Effect of melaxen and valdoxan on free radical processes intensity, aconitate hydratase activity and citrate content in rats tissues under hyperthyroidism].

The influence of melaxen and valdoxan on the biochemiluminescence parameters, aconitate hydratase activity and citrate level in rats heart and liver during development of experimental hyperthyroidism has been investigated. Administration of these substances promoted a decrease of biochemiluminescence parameters, which had been increased in tissues of rats in response to the development of oxidative stress under hyperthyroidism. Aconitate hydratase activity and citrate concentration in rats liver and heart, growing at pathological conditions, changed towards control value after administration of the drugs correcting melatonin level. The results indicate the positive effect of valdoxan and melaxen on oxidative status of the organism under the development of experimental hyperthyroidism that is associated with antioxidant action of melatonin.

The effect of melaxen on the activity of caspases and the glutathione antioxidant system in toxic liver injury.

A comparative study of the activity of caspase-1 and caspase-3, the glutathione antioxidant system and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase) and a study of DNA fragmentation in the blood serum of patients with chronic alcoholic hepatitis during basic treatment and combination therapy including melaxen have been carried out. It was found that the blood serum level of reduced glutathione, which decreases in pathology, increased more significantly in patients receiving melaxen as compared to the group of patients receiving the standard treatment. More significant changes in the activity of caspase-1 and caspase-3, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase toward the control values were observed during the combination therapy. The correction in the melatonin level under the influence of melaxen apparently had a positive effect on the free-radical homeostasis in patients, which resulted in more pronounced changes in the investigated parameters towards the normal values as compared to the basic treatment. KEY WORD S chronic alcoholic hepatitis; glutathione peroxidase; glutathione reductase; reduced glutathione; glutathione-S-transferase; caspases; melaxen.

Activity of the glutathione antioxidant system and NADPH-generating enzymes in blood serum of rats with type 2 diabetes mellitus after administration of melatonin-correcting drugs.

We studied the effects of epifamin and melaxen on serum content of reduced glutathione and activities of glutathione peroxidase, glutathione reductase, and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase) in rats with type 2 diabetes mellitus. The concentration of reduced glutathione was decreased in rats with this disease (by 1.8 times), but increased after treatment with epifamin and melaxen (by 1.6 and 1.7 times, respectively). Activities of glutathione peroxidase, glutathione reductase, and NADPH-generating enzymes returned to the control level. Correction of melatonin concentration after treatment with the test drugs was probably followed by inhibition of free radical processes. The observed changes were accompanied by normalization of activity of the glutathione antioxidant system and NADPH-generating enzymes required for normal function of this system.

[Effect of melatonin on antioxidant state under type ii diabetes at rat].

The effect of melatonin on the intensity of free radical processes and activities of superoxide dismutase (SOD, EC 1.15.1.1.) and catalase (EC 1.11.1.6) has been investigated in liver and blood serum of rats with diabetes mellitus type II. The development of diabetes was accompanied by the increase in biochemiluminescence parameters and the enzyme activities studied. Melatonin administration changed the parameters studied towards control values.

Intensity of Free Radical Processes in Rat Liver under Type 2 Diabetes and Introduction of Epifamin.

The effect of epifamin on free radical processes, the activity of caspase-1 and -3, aconitate hydratase and citrate content in rat's liver at experimentally induced type 2 diabetes mellitus (T2DM) was studied. The action of epifamin at T2DM leads to a decrease in biochemiluminescence parameters, characterizing the intensity of free radical processes, and changes in aconitase activity and citrate level towards the control. Activities of caspase-1 and caspase-3 in the tissue decreased by a factor of 2.4 and 1.6 in comparison with the levels at the disease. Apparently, epifamin-mediated correction of the level of melatonin, providing a significant antioxidant effect, promotes positive action on the free radical homeostasis.

[Catalytic properties of glutathione reductase from rats liver at norm and toxic hepatitis].

Homogeneous preparations of liver glutathione reductase (GR, EC 1.6.4.2.), obtained from control rats and animals with toxic hepatitis, catalytic properties of this enzyme have been investigated. A number of the enzyme properties did not change under conditions of hepatitis. These included electrophoretic mobility (R(f) = 0.23 +/- 0.01), molecular mass (104 +/- 5.20 kDa), pH-optimum (7.4 +/- 0.37). There was similarity in pK values of functional groups. At the same time, decrease in affinity of enzyme to a substrate and coenzyme and occurrence substrate-linked inhibition was observed under conditions of this pathology. There were some differencies in regulation of GR activity by metabolites of tricarboxylic acid cycle.

Effect of N-[Imino(4-morpholyl)methyl]guanidine on the oxidative status in rats with toxic hepatitis.

The hepatoprotective and antioxidant properties of a synthetic biguanide N-[imino(4-morpholyl)methyl]guanidine (IMMG) were prognosticated by the method of computer prediction. Administration of IMMG was accompanied by a decrease in serum transaminase activity in rats with toxic hepatitis, which reflects inhibition of hepatocyte cytolysis. IMMG treatment was followed by a decrease in biochemiluminescence parameters reflecting the intensity of free radical oxidation. We revealed an increase in activity of aconitase, which was reduced during toxic hepatitis. The content of citrate in the liver and serum was returned to normal under these conditions. IMMG also increased activities of superoxide dismutase and catalase and total antioxidant activity in rat liver. Our results suggest that the hepatoprotective effect of IMMG is associated with its antioxidant activity.