Effect of delta sleep-inducing peptide on the expression of antioxidant enzyme genes in the brain and blood of rats during physiological aging.

Subcutaneous injections of exogenous delta sleep-inducing peptide in a dose of 100 µg/kg (monthly, 5-day courses) to rats of various age groups (2-24 months) were followed by an increase in the expression of genes for SOD 1 (Sod1) and glutathione peroxidase 1 (Gpx1) in the brain and nucleated blood cells. The expression of these genes was shown to decrease during physiological aging of the body.

[Rat tissues antioxidant status correction by peptide delta sleep during physiological aging of the organism].

It is shown that exogenous delta-sleep inducing peptide increases glutathione antioxidant system level in rat tissues at different stages of ontogenesis, by subcutaneous injection to rats 2-24 months postnatal development in a dose of 100 mg/kg animal body weight by courses of 5 consecutive days per month, and this effect is especially marked in non-renewable postmitotic tissues.

[Influence of delta-sleep inducing peptide on the state of lysosomal membranes and intensity of lysosomal proteolysis in different rat tissues during physiological aging of the organism].

It is shown that subcutaneous injection of exogenous delta-sleep inducing peptide (DSIP) to rats aged 2-24 months in a dose of 100 µg/kg animal body weight by courses of 5 consecutive days per month has a stabilizing effect on the state of lysosomal membranes in rat tissues (brain, heart muscle and liver) at different ontogenetic stages, and this effect is accompanied by increasing intensity of lysosomal proteolysis in these tissues.

[Influence of delta-sleep peptide on the enzymes activity of mitochondrial electron transport chain in various rat tissues during aging of the organism].

It is shown that subcutaneous injection of exogenous delta-sleep inducing peptide (DSIP) to rats aged 2-24 months in a dose of 100 µg/kg animal body weight by courses of 5 consecutive days per month has a stabilizing effect on the NADH-dehydrogenase activity in the mitochondrial fractions of various tissues, which together with increasing capacity of the antioxidant system should reduce the production of free radicals and their adverse action on cells macromolecule, herewith the activity of succinate dehydrogenase did not change.

[Metabolic effects of delta-sleep inducing peptide during physiological aging of the organism].

Subcutaneous injection of delta-sleep inducing peptide (DSIP) to postnatal rats (aged from 2 to 24 months) during 5 consecutive days every months at a dose of 10 microg/100 g body weight favors normalization of the age-related changes in carbohydrate metabolism and shows hypoglycemic effect, as manifested by a decrease in the level of glycosylated hemoglobin in erythrocytes of test rats. The administration of DSIP in postnatal rats of different age also led to a decrease in serum total lipid level, total cholesterol level, and atherogenicity index and an increase in the level of high-density lipoprotein cholesterol.

[Olygopeptide KND as a putative endogenous prototype of delta sleep inducing peptide (DSIP). Comparative study of biological properties].

We have undertaken a comparative study on physiological activity of well known neuropeptide DSIP (WAGGDASG E) and new closely related peptide KND (WKGGNASGE) in vivo assays. The sequence of K2, N5-DSIP (KND) was found recently by the computer search for DSIP homologous sequences in available nucleotide and protein databases at 324-332 site of Lysine-specific demethylase 3 B (EC 1.14.11, Swiss-Prot: Q7LBC6.1, 1-1761aa). This human lysine-specific histone demethylase is a representative of the recently discovered family of so called JmjC-domain-containing histone demethylases encoded by JMJD1B gene and ubiquitously expressed in tissues of various mammalian species. Biological investigations performed in this work confirm our preliminary data that DSIP-related peptide KND exhibits the similar biological properties in comparison with DSIP. Assessed by us antioxidative, anticonvulsive and behavioral effects of KND were even more expressed than in DSIP case. These results provide the additional evidences to support our suggestion that KND can be a possible endogenous prototype of "real" DSIP.

Effect of delta sleep-inducing peptide on oxidative modification of proteins in rat tissues and blood during physiological aging.

Accumulation of oxidized proteins (evaluated by the levels of carbonyl and SH groups) in tissues of 2-24-month-old rats (spleen>myocardium>testicles>liver>skeletal muscles) has been demonstrated. Exogenous delta sleep-inducing peptide injected subcutaneously to rats of different age in a dose of 100 µg/kg by monthly 5-day courses protected proteins of the studied tissues from oxidation; its effect was tissue-specific. Delta sleep-inducing peptide exhibited a hypoglycemic effect: it prevented nonenzymatic glycosylation of hemoglobin and reduced the level of defective protein molecules during aging.

[Effect of delta-sleep inducing peptide on the functional activity of some organs and tissues of rats during physiological aging].

The authors show that exogenous delta-sleep inducing peptide (DSIP) injected subcutaneously to the rats in the age of 2-24 months of postnatal development in a dose of 100 mg/kg of animal body weight in courses for 5 consecutive days every month, has a hepatoprotective effect. DSIP does not affect the functional activity of the pancreas, and is not involved in the regulation of calcium homeostasis in the physiological aging of the organism.

[Mechanism of delta-sleep inducing peptide geroprotective activity].

It is shown that the subcutaneous injection to the rats in the age from 2 to 24 months during 5 consecutive days every month with 10 microg/100 g body weight of delta-sleep inducing peptide (DSIP) suppresses lipid peroxidation preventing the increasing of malonic dialdehyde level in rats tissues and plasma, possesses a powerful antioxidant effect, which is realized by means of the activation of different endogenous antioxidant defense system of cell and extracellular fluid, including high- and low-molecular regulators of free radical processes. DSIP exerts stimulating influence upon the superoxid-dismutese, catalase, ceruloplasmin activities as well as the level of nonenzymatic antioxidants--urea and uric acids, because during organism aging the antioxidant defense systems are being suppressed. DSIP increases the volume of tissues and blood endogenous antioxidant defense system mainly by means of enzymatic antioxidant system, especially during later ontogenesis.

[Effect of delta-sleep-inducing peptide on trypsin and pronase E activities in a model experiment]. / Vliianie del'ta-son indutsiruiushchego peptida na aktivnost' tripsina i pronazy E v model'nykh opytakh.

A delta-sleep-inducing peptide in various concentrations inhibits the pharmacological activity of trypsin and pronase E under experimental conditions.

[Free radical mechanism of the cold stress development in rats]. / Svobodnoradikal'nyi mekhanizm razvitiia kholodovogo stressa u krys.

Development of cold stress in rats is characterized by sharp activation of lipid peroxidation accompanied by a considerable increase of the diene conjugates level and Schiff bases in tissues of brain, liver and in erythrocytes. There is a shift in the prooxidant--antioxidant balance of the organism in the form of amplification of xanthine oxidase prooxidant enzymatic activity in the brain and liver, and a decrease of myeloperoxidase activity in blood neutrophiles of rats. The attrition at cold stress, mainly, of enzymatic endocellular antioxidant system as the result of inhibition of superoxide dismutase, catalase, glutathione reductase activities in brain, liver and erythrocytes is indemnified by activation of non-enzymatic antioxidant mechanisms. In conditions of cold stress, destabilization of erythrocyte membranes of rats described by a decrease of the microviscosity of protein-lipid contact zones and reduction of degree of immersing of proteins in lipid membrane owing to exhibiting proteins from the hydrophobic zone of membranes, or their aggregate, increase of polarity of lipid phase and negative surface charge, is marked.

[Features of regulating delta sleep-inducing peptide by free radical processes in tissue and erythrocyte membranes in intact animals and under stress]. / Osobennosti reguliatsii del'ta-son indutsiruiushchim peptidom svobodnoradikal'nykh protesessov v tkaniakh i membranakh éritrotsitov intaktnykh zhivotnykh i pri stresse.

In activity the comparative analysis of metabolic effects delta--sleep inducing peptide (DSIP) in tissues and erythrocytes of intact rats and under cold stress is conducted. The regulation effect of DSIP in attitude of free radical processes will be realised through modulation the prooxidant--antioxidant balance: both for intact animal, and at stress. Exogenous DSIP increases the antioxidant system activity in tissues of brain, liver and blood in standard conditions and under cold stress. The anti-stress effect of DSIP is directed as on increase of power endogenic enzymatic antioxidant system activity, specially glutathione peroxidase activity, and not enzymatic of antioxidant protection. The DSIP renders different influence on activity of prooxidant enzymes: for intact animal boosts the myeloperoxidase activity in blood neutrophils, not rendering essential influencing on the xanthine oxidase activity in tissues of brain, liver and activates the myeloperoxidase activity, depresses the xanthine oxidase activity for rats at stress. The membranotropic effect of DSIP in the norm and under stress is connected to increase of stability of protein--lipid interplays. The membranostabilizing effect of DSIP in conditions of stress is characterized decrease of polarity of lipid phase and negative surface charge of erythrocyte membranes, modified in course of lipid peroxidation.

[Pharmacological efficacy of delta sleep-inducing peptide in experimental acute pancreatitis]. / Farmakologicheskaia éffektivnost' del'ta-son indutsiruiushchego peptida pri éksperimental'nom ostrom pankreatite.

The development of experimental acute pancreatitis (EOP) in rats is accompanied by (i) intensification of the lipid peroxidation (LPO) process and the accumulation of malonic dialdehyde (MDA, an LPO product) in the tissues of pancreas, liver, and kidney and in the blood serum, (ii) destabilization of membranes and reduction of the osmotic resistance of erythrocytes (ORE), (iii) increase in the concentration of extracorpuscular hemoglobin (ECH) and medium-molecular-weight molecules (MWM) in the blood serum, and intensification of protein autolysis in tissues. Preliminary triple intraperitoneal administration of a delta-sleep-inducing peptide (DSIP) in a dose of 12 micrograms/100 g body weight to the test rats with EOP stabilized LPO, improved the erythrocyte membrane structure, reduced the MDA level in tissues and blood serum, increased ORE, reduced the ECH and MWM level in the blood, and decreased the protein autolysis rate in tissues.

[Effects of inhibitors of angiotensin-converting enzyme combined with antagonists of angiotensin II receptors on endothelial function in patients with chronic cardiac insufficiency]. / Vliianye ingibitorov angiotenzinprevrashchaiushchego fermenta v sochetanii s antagonistami retseptorov angiotenzina II na funktsional'noe sostoianie endoteliia u bol'nykh s khronicheskoi serdechnoi nedostatochnost'iu.

Effects were studied of a combined therapy with inhibitors of the angiotensin-converting enzyme and antagonists of receptors to angiotensin II on the functional condition of the endothelium in patients with chronic cardiac insufficiency (CCI). Recordable in the study was a noticeable decrease in the level of endothelin-1 and higher values for the concentration of 6-keto-prostaglandin (PGF1 alpha) and cGMP. In that way, administration of inhibitors of the angiotensin-converting enzyme combined with antagonists of receptors to angiotensin II has, been shown to considerably improve the endothelial function in CCi patients, which fact will, we believe, help in raising clinical effectiveness of the above combined medication.

Regulation of free radical processes by delta-sleep inducing peptide in rat tissues under cold stress.

An intraperitoneal injection of an exogenous delta-sleep inducing peptide (DSIP) at a dose of 12 microg/100 g body weight shifted the prooxidant-antioxidant balance of free radical process (FRP) in tissues and erythrocytes of rats: the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and the concentrations of antioxidants (reduced glutathione in particular) increased. The DSIP stimulated the myeloperoxidase activity in blood neutrophils and had no effect on the activity of xanthine oxidase, a prooxidant enzyme, in the brain and liver. Cold stress displaced the prooxidant-antioxidant balance by increasing the xanthine oxidase activity in tissues and decreasing the myeloperoxidase activity in blood neutrophils; it also inhibited the enzyme antioxidant activities in tissues and erythrocytes that was neutralized by an increased ceruloplasmin activity in blood plasma and by an elevated level of antioxidants in rat blood and tissues. Preliminary administration of DSIP to animals exposed to cold stress restored the prooxidant-antioxidant balance: it normalized the myeloperoxidase activity in blood neutrophils, decreased the xanthine oxidase activity, and increased the activity of antioxidant enzymes in tissues and erythrocytes restoring the antioxidant level. The molecular regulation mechanism of free radical processes by DSIP in tissues under stressful conditions is discussed.

The effects of delta sleep-inducing peptide on the intensity of lipid peroxidation and xanthine oxidase activity in rat tissues during cold stress.

Exogenous delta sleep-inducing peptide given i.p. to intact rats at a dose of 12 microg/100 g decreased the levels of diene conjugates and Schiff bases in liver and brain tissues and had no effect on xanthine oxidase activity in these tissues. Cold stress was accompanied by increases in xanthine oxidase activity in rat liver and brain, with a consequent accumulation of diene conjugates and Schiff bases, as compared with intact animals. Preliminary administration of delta sleep-inducing peptide before three days of cold stress led to decreases in xanthine oxidase activity and lipid peroxidation products in the liver and brain, as compared with values in stressed rats. The protective effect of delta sleep-inducing peptide in stress is discussed.

[The effect of angiotensin-II receptor antagonists on the vasoconstriction mechanisms in chronic heart failure]. / Vliianie antagonistov retseptorov angiotenzina II na mekhanizmy vazokonstriktsii pri khronicheskoi serdechnoi nedostatochnosti.

Overall thirty-two patients with chronic heart failure (CHF) II-IV FC according to NYHA classification were studied for effects of irbesartan, an antagonist of receptors to angiotensine II on mechanisms of vasoconstriction. Noted as a result of the treatment conducted was a significant reduction in the content of vasoconstrictors of angiotensin II, vasopressin, and epinephrine as well as a tendency toward decrease in values for thromboxane A2 and adrenaline. Vasoconstrictor factors were found to have an important part in vascular control in realization of efficacy of irbesartan, an antagonist of receptors to angiotensin II, in CHF patients.

[Regulatory effect of delta sleep-inducing peptide on the activity of antioxidant enzymes in erythrocytes and tissues of rats during cold stress]. / Regulitornoe vliianie del'ta-son indutsiruiushchego peptida na aktivnost' antioksidantnykh fermentov v éritrotsitakh i tkaniakh krys pri kholodovom stresse.

Antioxidant system's state of erythrocytes and tissues in rats under normal and cold stress conditions was studied. Intraperitoneal injection of exogenic DSIP at the dose of 12 mkg/100 g body weight both, to intact and to cold-exposed animals results in the increase of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase activities and concentration of glutathione in red blood cells, liver and brain.

[Effect of delta sleep-inducing peptide on lipid peroxidation and xanthine oxidase activity in rat tissues during cold stress]. / Vliianie del'ta-son indutsiruiushchego peptida na intensivnost' lipopereokisleniia i aktivnost' ksantinoksidazy v tkaniakh krys pri kholodovom stresse.

I. p. administration of exogenous delta-sleep-inducing peptide (DSIP) decreased the amount of diene conjugates and Schiff bases in the liver and brain in rats. The xanthine oxidase activity, at that, did not change. Cold stress enhanced the xanthine oxidase activity well as the amount of diene conjugates and Schiff bases. Preliminary administration of the delta-sleep-inducing peptide to cold-exposed animals diminished the xanthine oxidase activity and lipid peroxidation in the liver and brain. Protective effects of the DSIP under stress is discussed.