Study of the Magnesium Comenate Structure, Its Neuroprotective and Stress-Protective Activity.

The crystal structure and the biological activity of a new coordination compound of magnesium ions with comenic acid, magnesium comenate, was characterized and studied. Quantitative and qualitative analysis of the compound was investigated in detail using elemental X-ray fluorescent analysis, thermal analysis, IR-Fourier spectrometry, UV spectroscopy, NMR spectroscopy, and X-ray diffraction analysis. Based on experimental analytical data, the empirical formula of magnesium comenate [Mg(HCom)2(H2O)6]·2H2O was established. This complex compound crystallizes with eight water molecules, six of which are the hydration shell of the Mg2+ cation, and two more molecules bind the [Mg(H2O)6]2+ aquacation with ionized ligand molecules by intermolecular hydrogen bonds. The packing of molecules in the crystal lattice is stabilized by a branched system of hydrogen bonds with the participation of solvate water molecules and oxygen atoms of various functional groups of ionized ligand molecules. With regard to the biological activity of magnesium comenate, a neuroprotective, stress-protective, and antioxidant effect was established in in vitro and in vivo models. In in vitro experiments, magnesium comenate protected cerebellar neurons from the toxic effects of glutamate and contributed to the preservation of neurite growth parameters under oxidative stress caused by hydrogen peroxide. In animal studies, magnesium comenate had a stress-protective and antioxidant effect in models of immobilization-cold stress. Oral administration of magnesium comenate at a dose of 2 mg/kg of animal body weight for 3 days before stress exposure and for 3 days during the stress period led to a decrease in oxidative damage and normalization of the antioxidant system of brain tissues against the background of induced stress. The obtained results indicate the advisability of further studies of magnesium comenate as a compound potentially applicable in medicine for the pharmacological correction of conditions associated with oxidative and excitotoxic damage to nerve cells.

Role of the Nrf2/ARE Pathway in the mtDNA Reparation.

Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix, in close proximity to major sources of reactive oxygen species (ROS) in the cell. This makes mtDNA one of the most susceptible components to damage in the cell. The nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway is an important cytoprotective mechanism. It is well-studied and described that Nrf2 can regulate the expression of mitochondrial-targeted antioxidant systems in the cell, indirectly protecting mtDNA from damage. However, the Nrf2/ARE pathway can also directly impact on the mtDNA repair processes. In this review, we summarize the existing data on the impact of Nrf2 on mtDNA repair, primarily base excision repair (BER), as it is considered the main repair pathway for the mitochondrial genome. We explore the crosstalk between Nrf2/ARE, BRCA1, and p53 signaling pathways in their involvement in maintaining mtDNA integrity. The role of other repair mechanisms in correcting mismatched bases and double-strand breaks is discussed. Additionally, the review addresses the role of Nrf2 in the repair of noncanonical bases, which contribute to an increased number of mutations in mtDNA and can contaminate the nucleotide pool.

8-Oxoguanine-DNA-Glycosylase Gene Polymorphism and the Effects of an Alternating Magnetic Field on the Sensitivity of Peripheral Blood.

BACKGROUND: The production of reactive oxygen species (ROS) in animals and cells often results from exposure to low-intensity factors, including magnetic fields. Much of the discussion about the initiation of oxidative stress and the role of ROS and radicals in the effects of magnetic fields has centered on radical-induced DNA damage. METHODS: The DNA concentration in the final solution was determined spectrophotometrically. Typing of the polymorphic variant rs1052133 of the 8-oxoguanin DNA glycosylase (hOGG1) gene was performed by polymerase chain reaction. An enzyme immunoassay was performed to determine the level of 8-oxyguanine in DNA. To process samples exposed to an alternating magnetic field, the authors developed a device for the automated study of biological fluids in an alternating magnetic field. The content of hydrogen peroxide in aqueous solutions of DNA was determined using the spectrophotometric method. RESULTS: It was experimentally determined that an increase in the concentration of hydrogen peroxide in an aqueous medium by 3-5 times under the action of a low-frequency magnetic field reduces the resistance of the genomic material to oxidative modification and the accumulation of 8-oxyguanine in DNA. A model is proposed for the mechanism of action of a low-frequency magnetic field on aqueous solutions of nucleic acids and proteins, which satisfies the model of a chemical oscillator for the transformations of reactive oxygen species in an aqueous medium. The model illustrates the oscillating nature of the processes occurring in an aqueous solution of DNA and makes it possible to predict changes in the concentration of hydrogen peroxide in an aqueous solution of biopolymers, depending on the frequency of the acting low-intensity magnetic field. CONCLUSIONS: The key element in the mechanisms involved in the effects of low-intensity magnetic field on living systems is the occurrence of ROS generation in the aquatic environment of chemical oscillators, in which the competition of physical and chemical processes (electron transfers, reactions of decay and addition of radicals, spin magnetically induced conversion, synthesis, and decay of the longest-lived form-hydrogen peroxide) is controlled by a magnetic field.