According to one hypothesis, Parkinson's disease pathogenesis is largely caused by dopamine catabolism that is catalyzed on mitochondrial membranes by monoamine oxidase. Reactive oxygen species are formed as a byproduct of these reactions, which can lead to mitochondrial damage followed by cell degeneration and death. In this study, we investigated the effects of administration of the mitochondrial antioxidant SkQ1 on biochemical, immunohistochemical, and behavioral parameters in a Parkinson-like condition caused by protoxin MPTP injections in C57BL/6 mice. SkQ1 administration increased dopamine quantity and decreased signs of sensory-motor deficiency as well as destruction of dopaminergic neurons in the substantia nigra and ventral tegmental area in mice with the Parkinson-like condition.
The review presents currently available data on the biological role of 8-oxo-2'-deoxyguanosine. This compound has been successfully and for a long time used as a biomarker of oxidative stress and diseases associated with it. However, in recent years an increasing number of publications has appeared reporting that 8-oxo-dG is not simply a byproduct of oxidation processes, but is of great biological importance. It is assumed that it is involved in the regulation of gene expression, in some processes of DNA repair, in the control of inflammatory and autoimmune reactions, and in the activation of antioxidant systems. Probably there is a prospect of applying 8-oxo-2'-deoxyguanosine as a drug.
A preparative method for the synthesis of 8-oxo-2'-deoxyguanosine (8-oxo-dG) giving a high yield up to 80% and suitable for laboratory use is suggested. The urgency of the development of this method is associated with the need to obtain large quantities of 8-oxo-dG for the study of biological and pharmaceutical activity. Evidence of this need was obtained in the last decades, when the mechanisms of the interface of DNA repair with intracellular signaling through 8-oxo-dG were discovered and its anti-inflammatory and protective effects were revealed. The suggested method is based on the scheme used to prepare 8-oxo-dG-containing oligonucleotides, but has a number of important modifications. The use of N,N-dimethylformamide as a solvent makes it possible to increase the yield of the nucleophilic substitution reaction and avoid expensive and complicated further purification of silver acetate. Control of the reaction kinetics allows achieving the maximum yield and purity of the product. Alkaline hydrolysis, in contrast to ammonolysis, provides complete and rapid removal of acyl groups, and reversed-phase chromatography on silanized silica gel is an effective and inexpensive method of purification. Such a purification scheme minimizes contamination of the product with residual organic solvents, which is important for biological experiments. From the economic point of view, it is advantageous because of the absence of expensive solvents and the possibility of reusing the carrier. The method makes it possible to obtain pure 8-oxo-dG in preparative amounts and exceeds both its prototype and other existing techniques in the final output. Some intermediate compounds and significant methodological features of the reaction are described.
The study is devoted to 8-oxo-2'-deoxyguanosine (8-oxo-dG), which is used as a biomarker of oxidative damage to DNA and its associated diseases. The study is based on the hypothesis put forward by the authors about the ability of 8-oxo-dG, which is the main product of DNA oxidation, to act as a signal molecule that activates cell resistance to nonspecific stress and DNA repair. In addition to studying the molecular mechanisms of the action of 8-oxo-dG, the authors have carried out an investigation of the effects that they caused on the organism level.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.