Cardioprotective Effect of 2-Ethyl-3-Hydroxy-6-Methylpyridinium 2-Nitroxysuccinate Against Adrenaline/Hydrocortisone-Induced Myocardial Ischemia in Mice: Modulation of Free-Radical Processes in Biomembranes and Monoamine Oxidase A Activity.

Oxidative stress (OS) plays a key role in the development of cardiovascular diseases (CVD) in three major ways: reactive oxygen species (ROS)-induced reduction of nitric oxide (NO) bioavailability, ROS-induced inflammation and ROS-induced mitochondrial dysfunction. Oxidation of lipid molecules under the action of ROS leads to damage to membrane structures, changes the functioning of membrane-bound enzymes, and impairs membrane permeability and stability. An increase in OS results in the occurrence of endothelial dysfunction and drug tolerance, side effects, requiring discontinuation of drugs. All of these are significant problems of cardiotherapy. Therefore, the search for new alternative NO donors continues. The present research was aimed at studying the protective effect of 2-ethyl-3-hydroxy-6-methylpyridinium 2-nitroxysuccinate (NS) on the cardiovascular system on mouse myocardial ischemia (MI) model. The NS hybrid molecule includes a synthetic vitamin B6 analog 2-ethyl-3-hydroxy-6-methylpyridine (an antioxidant) and 2-nitroxysuccinic acid (a source of nitric oxide). Using the electron paramagnetic resonance (EPR) method and biochemical methods, we showed that the pronounced ability of NS to release NO is favorably combines with the capacity to prevent OS due to mechanisms such as suppression of the lipid peroxidation (LPO) process, antiradical activity and inhibition of the mitochondrial membrane-bound monoamine oxidase A (MAO-A). Using histological methods, we established that the administration of NS (10 mg/kg, i.p.) reduces the number of ischemic fibers and protects cardiomyocytes against ischemia injury. Thus, the complex protective effect allows us to consider NS as an alternative NO donor and a candidate for the development of a new pharmaceutical agent for the treatment of CVD.

Influence of constant lightning on liver health: an experimental study.

Light pollution has become a serious problem in many urbanized areas of the world. The impact of prolonged exposure to light and consequent disruption of natural circadian rhythms has significant health implications. The current study was undertaken to evaluate the effect of prolonged exposure to light, simulating urban light pollution, on liver health. In order to evaluate the effect of prolonged exposure to light, we examined the morphofunctional state, immunohistochemical and micromorphometric parameters of rat liver in normal conditions and following prolonged lighting exposure. Our results show that nocturnal light disruption triggers a cell death in the liver within 3 weeks (necrosis and apoptosis of hepatocytes) and stimulates a change in normal cellular karyometric parameters. At the same time, intracellular regeneration takes place within the organ, which manifests through hepatocyte hypertrophy. Under the influence of constant illumination, the circadian rhythms (CRs) of the size of hepatocytes and their nuclei are restructured, and the rhythm of the nuclear-cytoplasmic ratio is destroyed. The destruction of the CR of expression of p53 and Ki-67 also occurs against the background of the rearrangement of the daily rhythmicity of Per2 and Bmal1. The revealed changes in the morphofunctional state of the liver under the influence of light pollution indicate that a violation of normal illumination regimes is a potent factor leading to significant structural changes in the liver.

Morphofunctional State and Circadian Rhythms of the Liver under the Influence of Chronic Alcohol Intoxication and Constant Lighting.

A study of the influence of chronic alcohol intoxication, constant illumination and their combined effects on the morphofunctional state of the rat liver and the circadian rhythms (CR) of the studied parameters of the organism was carried out. It was found that both alcohol and constant illumination caused significant changes in the structure of the liver, as well as in the circadian rhythmicity of micromorphometric parameters of hepatocytes, ALT, and total and direct bilirubin rhythms; however, the combined effects of ethanol and constant illumination had the most significant effect on the studied parameters of the organism. These two factors caused disturbances in the circadian rhythms of the micromorphometric parameters of hepatocytes, disruption of the circadian rhythms of total protein, albumin, AST, ALT, and direct and total bilirubin, as well as disturbances in the expression and rhythmicity of the studied clock genes against a background of the development of an inflammatory process in the liver.