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1.
Vestn Ross Akad Med Nauk ; (2): 55-62, 2007.
Article in Russian | MEDLINE | ID: mdl-17396564

ABSTRACT

Phytogenous flavonoid-containing agents (PFCA) are able to initiate electron flow bypassing the NAD-dependent region of respiratory chain, which is related with the activity of DT-diaphorase catalyzing two-electron reduction of quinones to hydroquinones and hydrogen peroxide in the presence of NADH and oxygen. This property is dramatically potentiated under the conditions of suppressed electron transport function of mitochondrial enzyme complex I (MEC I). In this process, part of the flow goes to the cytochrome region of respiratory chain and provides recovery of the MEC II and MEC III coupling function. The other part forms a flow of free oxidation which can perform as an additional mechanism normalizing the cell redox potential and aimed at decreasing intracellular acidosis under the conditions of MEC I bypassing. The energotropic effect of PFCA under the conditions of blocked MEC I is best evident at low PFCA concentrations. The ratio of coupled to free oxidation in the presence of PFCA depends on PFCA concentration. At low PFCA concentrations and oxidation of NAD-dependent substrates, both pathways become potentiated to an approximately similar extent, although the coupled oxidation pathway is generally activated earlier. At high PFCA doses, the increase in free oxidation pathway predominates and may result in toxic side effects.


Subject(s)
Antioxidants/pharmacology , Energy Metabolism/drug effects , Flavonoids/pharmacology , Hypoxia/prevention & control , Humans
2.
Article in Russian | MEDLINE | ID: mdl-14681966

ABSTRACT

Fifty-one blood samples of Russian patients with sporadic motor neuron disease were examined for mutations in Cu/Zn superoxide dismutase (SOD-1) gene. One female patient with amyotrophic lateral sclerosis (ALS) was heterozygous for G12R mutation. This patient suffered from ALS with cervical cord onset, pyramidal variant and fast progression. Mutation was also detected in her healthy son. Earlier, such mutation was described in 5 Italian patients with slow progressive ALS. Also, D90A SOD-1 gene associated haplotypes of the female ALS patients previously examined by the authors have been analyzed. A homozygous female patient with ALS was characterized by typical lumbar onset and extremely slow progression, as well as a female patient with heterozygous mutation and moderate progression carried so-called "Scandinavian" haplotype. To our knowledge, it is the first report on the finding of the haplotype considered as a "protective" one in the subjects heterozygous for D90A mutation with clinical symptoms of ALS. Mechanisms of "protective" influence of this haplotype on ALS course are not yet elucidated. Our finding suggests that the presence of "Scandinavian" haplotype does not completely protect from the disease development in patients exposed to other more pathogenic causative factors. This assumption is in line with modern conceptions on motor neuron disease as a complicated multifactor disorder.


Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Motor Neuron Disease/genetics , Mutation , Superoxide Dismutase/genetics , Aged , Aged, 80 and over , Arginine/genetics , Copper , Disease Progression , Electromyography , Exons/genetics , Female , Glycine/genetics , Haplotypes , Heterozygote , Homozygote , Humans , Male , Middle Aged , Polymorphism, Genetic , Risk Factors , Russia , Zinc
3.
Bioorg Khim ; 26(6): 466-70, 2000 Jun.
Article in Russian | MEDLINE | ID: mdl-10923196

ABSTRACT

New derivatives of proto- and deuterohemin IX containing tri- and tetrazole rings were synthesized and characterized. A pronounced antioxidant activity was found for these compounds in the Fe(II)/ascorbate-dependent system of lipid peroxidation in murine liver homogenates.


Subject(s)
Antioxidants/chemical synthesis , Antioxidants/pharmacology , Azoles/chemistry , Hemin/chemical synthesis , Hemin/pharmacology , Animals , Antioxidants/chemistry , Hemin/chemistry , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/metabolism , Mice , Rats
5.
Biull Eksp Biol Med ; 103(6): 685-7, 1987 Jun.
Article in Russian | MEDLINE | ID: mdl-3593951

ABSTRACT

A comparative study of antihypoxic activity of five and two cytochrome c derivatives was performed during their single prophylactic administration on the model of acute hypobaric hypoxia (AHBH) and during rehabilitation period after AHBH, respectively. Antihypoxic efficiency of cytochrome c derivatives was shown to be dependent on doses, time of drug administration, and type of experimental animal resistance. The heme-nonapeptide of cytochrome c proved to be of maximum efficiency during prophylactic administration and rehabilitation period after AHBH.


Subject(s)
Hypoxia/drug therapy , Peroxidases/therapeutic use , Acute Disease , Animals , Disease Susceptibility , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Hypoxia/prevention & control , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Time Factors
6.
Biofizika ; 31(2): 231-6, 1986.
Article in Russian | MEDLINE | ID: mdl-3008856

ABSTRACT

Changes observed in CD- and absorption spectra of cytochrome c solubilized in reversed micelles AOT showed significant structural transformations of protein in the region of the active centre and particularly revealed a replacement of the sixth ligand of heme iron. These changes also affected the redox properties of cytochrome c.


Subject(s)
Cytochrome c Group/analysis , Surface-Active Agents , Animals , Binding Sites , Circular Dichroism , Horses , Micelles , Myocardium/enzymology , Oxidation-Reduction , Protein Conformation , Solvents
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