В статье описана методика инкапсулирования противовоспалительного додекапептида инграмон в микросферы биоразлагаемого сополимера молочной и гликолевой кислот (ПЛГА), обеспечивающая пролонгированное высвобождение данного пептида за срок до 28 дней. Методика позволяет достигать эффективности инкапсуляции свыше 90 % и пригодна для получения инъекционной суспензии, удовлетворяющей требованиям Государственной фармакопеи РФ. Охарактеризованы распределение пептида внутри полученных микросфер, профиль его высвобождения. Обнаружена тенденция к подавлению JE/CCL2-зависимой миграции моноцитов у мышей с предварительным (за 7 дней до эксперимента) введением инграмона-депо.

The changes of the 8-oxo-2'-deoxyguanosine (8-oxo-dG)/dG ratio in the DNA of laboratory mice hepatocytes under the influence of toxic stress were studied. It was shown that the injection of carbon tetrachloride causes the growth of 8-oxo-dG level. A rapid increase in the level of 8-oxo-dG in DNA occurs during the first day of the experiment at short-term toxic stress. Subsequently, 48 hours after the initial injection, the level of 8-oxo-dG decreases to the control values. This change in the value of the biomarker can be attributed to the activation of the reparative and antioxidant systems. The subsequent injection results again in an increase of 8-oxo-dG level, and the latter only increases thereafter. This reflects the exhaustion of the reparative potential of the organism and accompanies the progress of inflammation and pathological change of the liver tissue.

In this paper we studied the effect of melatonin at three concentrations on the formation of 8-oxo-2'-dioxyguanosine (8-oxo-dG) under the conditions of the Fenton reaction. Reproducible kinetic curve of 8-oxo-dG accumulation in this reaction was obtained by the method of reversedphase high performance liquid chromatography with amperometric detection. When adding melatonin in all three concentrations studied, there was a noticeable change in the shape of the kinetic curve with a significant decrease in the amount of detected 8-oxo-dG in most of its control points. This suggests the melatonin inhibition of 8-oxo-dG formation in the reaction and confirms the hypothesis of a direct, non-hormonal, antioxidant effect of melatonin. However, the dependence of the inhibitory effect of melatonin on its concentration is not a straight line. The higher of the studied concentrations of melatonin (60 mg/ml) gave the least pronounced effect.

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.