[The effect of antioxidants on in vivo and in vitro methemoglobin formation in erytrocytes of patients with Parkinson`s disease].

Methemoglobin formation was examined in erytrocytes of 16 patients with Parkinson`s disease (PD) (stage 3-4 by the Hoehn and Yahr scale). The patients receiving levodopa-containing drugs (madopar, nakom) were also treated with intramuscular injections of mexidol (daily dose 100 mg/day) for 14 days. Control group included 12 clinically healthy persons. The erythrocyte methemoglobin content was determined by electronic paramagnetic resonance (EPR) using the EPR signal intensity with g-factor 6.0. The methemoglobin content was significantly higher in erythrocytes of PD patients than in healthy donors. The complex therapy with mexidol normalized the methemoglobin content in erythrocytes of PD patients. Incubation in vitro of erythrocytes of donors and PD patients with acrolein increased the methemoglobin content, while incubation with carnosine normalized the methemoglobin content in erythrocytes of PD patients. Prophylactic (i.e. before acrolein addition) and therapeutic administration of carnosine to the incubation system with acrolein decreased the methemoglobin content to its initial level. Results of this study suggest that inclusion of the antioxidants mexidol and carnosine in the scheme of basic therapy of PD may reduce side effects associated with methemoglobinemia.

[Effect of L-lysine alpha-oxidase from Trichoderma cf. aureoviride Rifai ВКМF-4268D on pheochromocytoma PC12 cell line].

L-Amino acid oxidases (L-ААО, EC 1.4.3.2) comprise a group of flavoproteins, catalyzing oxidative deamination of L-alpha amino acids to the corresponding alpha-keto acids, NH3 and Н2О2. In most cases these enzymes present homodimeric molecules with a molecular mass of 100-150 kDa, which were shown to possess antiviral, antifungal and antitumor activity. L-lysine alpha-oxidase (LO) holds an outstanding place among this group of enzymes and its biological role may differ significantly from the other L-AAO, because it cleaves an essential amino acid - L-lysine without significant action on the other amino acids. Although much research has examined LO effects in the organism, the molecular basis of these effects is yet to be identified. To fill this gap, the present work addressed one of hypothetical mechanisms of LO biological action using the enzyme from Trichoderma cf. aureoviride Rifai ВКМF-4268D and rat pheochromocytoma PC-12 as a model cell line. Using flow cytometry a dose-dependent cytotoxicity of LO was shown. The significant growth of intracellular reactive oxygen species levels, detected by 2,7-dichlorodihydrofluorescein assay, implies generation of peroxide as one of the molecular mechanisms of LO cytotoxic action, although this does not rule out other probable ways of LO action in the organizm.

Effect of hypoxia on the state of tissues in SAMR1 and SAMP1 mice with various rates of aging.

Senescence-accelerated SAMP1 mice were more sensitive to the negative effect of hypobaric hypoxia than SAMR1 mice (control). Low-temperature EPR spectroscopy showed that high sensitivity of SAMP1 mice is related to the increased concentration of methemoglobin in the blood leading to hemic hypoxia. Proton magnetic relaxation study showed that the exposure of SAMP1 mice to hypoxia can cause cerebral edema.

Effects of carnosine on polyamine levels in red blood cells of patients with hypertonic discirculatory encephalopathy.

The levels of polyamines (putrescine, spermine, spermidine) in erythrocytes from patients with hypertonic discirculatory encephalopathy are reduced (by 37, 45, and 50%, respectively) in comparison with the corresponding parameters in the control group. Addition of carnosine to the treatment protocol for chronic brain ischemia normalized the content of putrescine and spermine. The mechanisms of carnosine influence on polyamine metabolism are discussed: trapping of acrolein, end-product of polyamine oxidation, and compensation of NMDA-receptor excitotoxicity.

Effect of delta sleep-inducing peptide on macromolecule biosynthesis in brain tissue of stressed rodents.

For evaluation of the nature of adaptogenic properties of delta sleep-inducing peptide we studied the effect of this substance on macromolecule biosynthesis in the brain of rats and mice exposed to burn injury and psychoemotional stress, respectively. Anabolic activity of delta sleep-inducing peptide depended on the purpose of adaptation corresponding to the type of stress.

[Changes in the intensity of free-radical reactions in the organs of rats under hypokinetic stress and with protection by the delta sleep-inducing peptide and its tyrosine-containing analog]. / Izmeneniia intensivnosti svobodnoradikal'nykh reaktsii v organakh krys pri gipokineticheskom stresse i zashchite del'ta-son-indutsiruiushchim peptidom i ego tirozinsoderzhashchim analogom.

Dynamics of the hypokinesia-induced changes of free radical and malonic dialdehyde content in brain, the changes of respiratory chain state and superoxide dismutase activity in liver of rats has been studied using ESR technique and biochemical methods. The effect of the preliminary injection of DSIP and its analogue ID-2 on these dynamics has also been studied. Using a model system constants of the interaction between DSIP or ID-2 and O2-. have been determined. The data point to the antioxidant effect of the administration of the peptides before hypokinesia. This suggests that the effect involves in mechanisms of the anti-stress action of these peptides.

[Use of gamma-aminobutyric acid from various sources in the synthesis of homocarnosine in the brain of animals of various ages]. / Ispol'zovanie razlichnykh istochnikov gamma-aminomaslianoi kisloty v sinteze gomokarnozina v mozga zhivotnykh raznogo vozrasta.

The dynamics and intensity of radiolabelled carbon incorporation from [14C] putrescine into homocarnosine in the brains of rats of various age have been studied. In the brains of 1-, 7-, and 2-day-old rats putrescine is the main GABA source for homocarnosine synthesis. In the brains of 14- and 31-day-old animals the GABA formed from glutamic acid participates in homocarnosine synthesis alongside with putrescine. In the brains of adult rats the rate of [14C] incorporation from glutamic acid into homocarnosine is 7 times as low as that of [14C] incorporation from putrescine.

[Antistressor effect of delta-sleep-inducing peptide in hypokinetic stress]. / Antistressornyi éffekt del'ta-son-indutsiruiushchego peptida pri gipokineticheskom stresse.

The influence of DSIP injection on the levels of neurotransmitters during hypokinetic stress was studied. It was shown that hypokinesia produced considerable changes in the levels of GABA glutamate, aspartate and homocarnosine. The injection of DSIP normalized the level of neurotransmitter amino acids. Administration of DSIP also reduced stress-induced changes in the activity of enzymes of GABA metabolism. Stress protective effect of DSIP was also demonstrated by normalising of the POL of lipids in brain.

[The effect of naloxone and delta-sleep inducing peptide on the homocarnosine content of brain tissue]. / Vliianie naloksona i del'ta-son-inutsiruiushchego peptida na soderzhaniie gomokarnozina v tkani golovnogo mozga.

The intraventricular and intravenous administration of naloxone was studied for its effect on the homocarnosine amount in cerebral hemispheres, striatum, hippocamp, hypothalamus, thalamus, cerebellum, medulla oblongata as well as in the spinal cord of rabbits. The intracysternal administration of naloxone decreases the homocarnosine amount in the striatum, hypothalamus, cerebellum and medulla oblongata. The intravenous administration of peptide exerts no statistically reliable effect on the homocarnosine content in the rabbit brain. The intraperitoneal administration of delta-sleep-inducing peptide increases sharply the homocarnosine content in the rat brain.

[Intensity of label incorporation from [1,4-14C]putrescine into homocarnosine in the brain of rats of various ages]. / Intensivnost' vkliucheniia metki iz [1,4-14C]putrestsina v gomokarnozin v mozgu krys razlichnogo vozrasta.

Intensity of 14C incorporation from the [1.4-14C]-putrescine to the homocarnosine and homocarnosine content in the brain of 1-, 7-, 14-, 21-day and adult rat were investigated. It is shown that dynamics of 14C incorporation from 1.4-14C-putrescine to the homocarnosine in the brain of rats of different age does not correlate with dynamics of homocarnosine content increase. The most significant activity of label incorporation from 14C-putrescine to the homocarnosine takes place in the brain of 1-, 21-day animals and adult rats.

[Protective effect of the neuropeptide homocarnosine in hyperbaric oxygenation]. / Protektornoe deistvie neiropeptida gomokarnozina pri giperbarooksigenatsii.

Homocarnosine, at a dose of 10 mg per 100 g of animal body mass administered intraperitoneally within 15 min before hyperbaric oxygenation with 0.7 MPa of oxygen, exhibited a protective effect. After administration of the neuropeptide into animals before hyperbaric oxygenation a latent period of oxygen convulsions was increased; content of homocarnosine and gamma-aminobutyric acid (GABA) was maintained at the level found in brain of control animals. In brain tissue of unprotected animals content of homocarnosine and GABA was decreased due to the oxygen treatment. GABA was less effective, its protective dose exceeded 10-fold the dose of homocarnosine. The neuropeptide exhibited antioxidant properties in reactions of lipid peroxidation under normal conditions and in hyperbaric oxygenation in vitro. The antioxidant activity of GABA was distinctly lower as compared with homocarnosine.

[Homocarnosinase activity in the rat brain areas kidneys under different states of hyperbarooxygenation]. / Gomokarnozinaznaia aktivnost' v otdelakh golovnogo mozga i pochkakh krys pri raznykh rezhimakh giperbarooksigenatsii.

The homocarnosinase activity in different brain areas and kidneys of the normal rats and under different conditions of hyperbarooxygenation are determined. The highest activity of this enzyme is observed in cerebellum. The high homocarnosinase activity is typical of kidneys as well. The action of oxygen in a dose of 0.425 MPa for 60 min (in the absence of convulsions) increases the homocarnosinase activity in the cerebral hemispheres by 18.6%, in the midbrain by 18.6%, in midbrain and diencephalon--by 56.5%, and in the medulla oblongata--by 40.6%. The homocarnosinase activity in the cerebellum decreases by 16.7%, in kidneys--by 18.5%. At the convulsive stage of oxygen intoxication caused by the effect of 0.7 MPa dose of oxygen the homocarnosinase activity in cerebral hemispheres rises by 158.5%, in the midbrain and diencephalon--by 141.5%, in the medulla oblongata by--161.1%. Under the same conditions homocarnosinase activity in the cerebellum is unchanged as compared with the control.

[Homocarnosine levels in various regions of the rat brain and blood in hypoxia and after hyperbaric oxygenation]. / Soderzhanie gomokarnozina v otdelakh mozga i krovi krys v sostoianii gipoksii i posle deistviia giperbaricheskoi oksigenatsii.

Content of homocarnosine was studied in rat brain departments and blood after hypoxia (9,000 m, 60 min) and hyperoxia (0.3 mPa of oxygen, 60 min) following the hypoxia. In hypoxia content of homocarnosine was unaltered in brain hemispheres and medulla oblongata, it was increased by 41% in midbrain and cerebellum and by 80% in blood. Simultaneous effect of hypoxia and hyperbaric oxygenation decreased the homocarnosine content in brain hemispheres by 22%, in midbrain and diencephalon by 61%, in medulla oblongata by 34%, in cerebellum by 66% and in blood by 39%. Thus, therapeutic doses of hyperbaric oxygenation did not normalize the homocarnosine content in brain of animals with hypoxia.

[Concentration of free amino acids and homocarnosine dipeptide in the cerebrospinal fluid of children with hydrocephalus]. / Soderzhanie svobodnykh aminokislot i dipeptida gomokarnozina v likvore detei s gidrotsefaliei.

The content of free amino acids and the dipeptide homocarnosine was examined in the cerebrospinal fluid of children with post-meningitis hydrocephalus. Of 17 identified amino acids the levels of threonine, methionine, leucine, alanine, lysine, histidine, glutamic acid and GABA appeared to be sharply changed. The homocarnosine level in the hydrocephalic children's CSF was found to be 10, and in hydrocephalic children with idiocy, 18 times higher than in the control.

[Content of homocarnosine, gamma-amino butyric acid and histidine in brain tissue of different age normal rabbits and under hyperoxia]. / Soderzhanie gomokarnozina, gamma-aminomaslianoi kisloty i gistidina v tkani mozga krolikov raznogo vozrasta v norme i pri giperoksii.

The content of homocarnosine, gamma-amino butyric acid and histidine was studied in the brain of newborn, 1, 7, 14, 21 and 30-day rabbits in normalcy and under hyperoxia. For 30 days of the postnatal life the amount of peptide in the animal brain is 2.5, histidine 1.6, gamma-amino butyric acid--2.2 times as high. At the preconvulsive stage of oxygen poisoning the content of homocarnosine lowers sharply in the brain of rabbits of all age groups. The most considerable decrease is observed in the brain of 14, 21 and 30-day rabbits by 53, 60 and 85%, respectively. The content of gamma-amino butyric acid lowers only in the brain of 21 and 30-day animals by 39 and 47%, respectively; the content of histidine in these animals under hyperoxia, vice versa, increases by 10 and 25%.