8-оксо-2’-дезоксигуанозин - биомаркер окислительного стресса

Free radical mechanism of a cell damage is one of the universal non-specific pathogenic pathways in a cause of many diseases, including cancer, neurodegenerative diseases, atherosclerosis and aging. So in nuclear and mitochondrial DNA, guanine hydroxylation to 8-position gives 8­hydroxy­2'­deoxyguanosine (8­OH­dG) and 8­oxo­7,8­dihydro­2'­deoxyguanosine (8­oxo­dG). These substances are one of the predominant products of free radical­induced oxidative damages. They are usually been applied as biomarkers of oxidative stress and carcinogenesis. The direct oxidation of guanine or incorrect inclusion of 8-oxo-dGTP from the nucleotide pool by polymerases, lead to a lack of specificity of the base pairing in DNA, favoring mutagenesis. Firstly 8-oxo-dG has been described by H. Kasai and S. Nishimura in 1983. Since then, this damage has been widely measured in various tissues and body fluids as blood, urine, brain, liver, and others. Today 8-oxo-dG is already used not only as a marker of oxidative stress, but also as a tool for prognosis of diseases and results of applied therapy. Now many efforts are focused on developing the procedure of measurement of 8-oxo-dG content in tissues and body fluids. In this paper we also discuss the role of the 8-oxo-dG as a biomarker of oxidative stress and a predictor of diseases and results of the applied therapy.8-Оксо-2’-дезоксигуанозин (8-oxo-dG) является преобладающей формой свободнорадикального повреждения ДНК. C момента его обнаружения в 1983 году, это соединение определяют в различных тканях и жидкостях организма: в крови, моче, мозге, печени и др. В данном обзоре рассматривается роль 8-oxo-dG в качестве биомаркера окислительного стресса, предиктора течения заболевания и успеха применяемой терапии у больных, а также методы, с помощью которых он сегодня детектируется в биологических образцах

Твердофазный синтез отрицательно заряженных олигомеров полиамидных миметиков нуклеиновых кислот

A Boc-protocol for manual solid-phase synthesis of novel sequences of negatively charged oligomeric polyamide mimetics of nucleic acids with a regular structure of the pseudopeptide backbone based on L-glutamic acid and glycine and having various positions of the carbethoxyethyl moiety was developed. Conditions for their cleavage from polymeric carrier, isolation and structure confirmation are presented.Разработан Вос-протокол ручного твердофазного синтеза новых последовательностей отрицательно заряженных олигомеров полиамидных миметиков нуклеиновых кислот с регулярной структурой псевдопептидного остова на основе L-глутаминовой кислоты и глицина и различным положением карбоксиэтильного остатка. Представлены условия для их удаления с полимерного носителя, выделения и доказательства структуры

Анализ содержания 8-оксо-2'-дезоксигуанозина в ДНК клеток мозга крыс при изучении защитного действия кортексина

The protective effect of cortexin was investigated with the use of acoustic stress hemorrhagic stroke model. A significant decrease of 8-oxo-2'-deoxyguanosine to 2'-deoxyguanosine ratio in the DNA molecule was shown using brain slices of cortexin treated Krushinsky-Molodkina rats.В работе изучено влияние защитного действия препарата кортексин на мозг крыс линии Крушинского-Молодкиной в условиях экспериментального геморрагического инсульта, вызван-ного акустическим стрессом. Показано значительное уменьшение отношения 8-оксо-2'-дезокси-гуанозина к 2'-дезоксигуанозину в ДНК клеток мозга крыс при применении кортексина

Определение отношения 8-оксо-2'-дезоксигуанозина к 2'-дезоксигуанозину в ДНК с помощью обращенно-фазовой ВЭЖХ в сочетании с амперометрической детекцией

The article presents an optimized method for the determination of the ratio of 8-oxo-2'-deoxyguanosine (formed in DNA due to the action of active forms of oxygen) to 2'-deoxyguanosine. The ratio was determined by reverse phase HPLC combined with amperometric detection. It was shown that the ratio increases upon oxidative stress caused by the action of large doses of ascorbic acid in samples of DNA isolated from the liver of experimental rats.В работе проведена оптимизация метода определения отношения 8-оксо-2'-дезоксигуанозина, образующегося в ДНК в результате действия активных форм кислорода, к 2'-дезоксигуанозину методом обращенно-фазовой ВЭЖХ в сочетании с амперометрической детекцией. Показано увеличение этого отношения при окислительном стрессе, вызванном действием больших доз аскорбиновой кислоты, в образцах ДНК, выделенных из печени экспериментальных крыс

Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy

Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies

8-Oxo-2’-deoxyguanosine – biomarker of the oxidative stress

Free radical mechanism of a cell damage is one of the universal non-specific pathogenic pathways in a cause of many diseases, including cancer, neurodegenerative diseases, atherosclerosis and aging. So in nuclear and mitochondrial DNA, guanine hydroxylation to 8-position gives 8­hydroxy­2'­deoxyguanosine (8­OH­dG) and 8­oxo­7,8­dihydro­2'­deoxyguanosine (8­oxo­dG). These substances are one of the predominant products of free radical­induced oxidative damages. They are usually been applied as biomarkers of oxidative stress and carcinogenesis. The direct oxidation of guanine or incorrect inclusion of 8-oxo-dGTP from the nucleotide pool by polymerases, lead to a lack of specificity of the base pairing in DNA, favoring mutagenesis. Firstly 8-oxo-dG has been described by H. Kasai and S. Nishimura in 1983. Since then, this damage has been widely measured in various tissues and body fluids as blood, urine, brain, liver, and others. Today 8-oxo-dG is already used not only as a marker of oxidative stress, but also as a tool for prognosis of diseases and results of applied therapy. Now many efforts are focused on developing the procedure of measurement of 8-oxo-dG content in tissues and body fluids. In this paper we also discuss the role of the 8-oxo-dG as a biomarker of oxidative stress and a predictor of diseases and results of the applied therapy

Solid-phase synthesis of negatively charged oligomeric polyamide mimetics of nucleic acids

A Boc-protocol for manual solid-phase synthesis of novel sequences of negatively charged oligomeric polyamide mimetics of nucleic acids with a regular structure of the pseudopeptide backbone based on L-glutamic acid and glycine and having various positions of the carbethoxyethyl moiety was developed. Conditions for their cleavage from polymeric carrier, isolation and structure confirmation are presented

8-Oxo-7,8-dihydro-2′-deoxyguanosine values measured in brain DNA of rats upon investigating cortexin protective action

The protective effect of cortexin was investigated with the use of acoustic stress hemorrhagic stroke model. A significant decrease of 8-oxo-2'-deoxyguanosine to 2'-deoxyguanosine ratio in the DNA molecule was shown using brain slices of cortexin treated Krushinsky-Molodkina rats