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Natural and chemically modified N-terminal galanin fragments (WTLNSAGYLLGPHA-OH (G1) and WTLNSAGYLLGPβAH-OH (G2), respectively) reduce functional and metabolic disturbances in the heart during experimental ischemia and reperfusion. The aim of this work was to examine whether these peptides and full-length rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, G3) decrease the formation of reactive oxygen species (ROS) and lipid peroxidation products in the heart with ischemia/reperfusion (I/R) injury. The peptides were synthesized by the automatic solid phase method using Fmoc technology. Their structure was identified by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experiments were performed on anaesthetized open-chest rats subjected to myocardial regional ischemia and reperfusion. The microdialysis method and the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin trap were used to monitor ROS content in the area at risk (AAR). Intravenous administration of G1, G2 or G3 after occlusion of coronary artery significantly decreased the content of DMPO-OH spin adduct in interstitium of the AAR during reperfusion compared to the control. These effects were accompanied by limitation of infarct size, reduction of the plasma activity of creatine kinase-MB and lactate dehydrogenase, and better preservation of the energy state of the AAR. In addition, peptides G2 and G3 significantly reduced the formation of thiobarbituric acid reactive substances in the AAR. The overall protective action of the peptides decreased in the order G2 > G3 > G1. The results suggest that pharmacological agonists of galanin receptors can be considered as promising agents to reduce oxidative stress in myocardial I/R injury.

It is shown that the inhalation of gaseous nitric oxide (gNO) or sprayed aqueous solutions of binuclear dinitrosyl iron complexes with glutathione or N-acetyl-L-cysteine by animals or humans provokes no perceptible hypotensive effects. Potentially, these procedures may be useful in COVID-19 treatment. The NO level in complexes with hemoglobin in blood decreases as the gNO concentration in the gas flow produced by the Plazon system increases from 100 to 2100 ppm, so that at 2000 ppm more than one-half of the gas can be incorporated into dinitrosyl complexes formed in tissues of the lungs and respiratory tract. Thus, the effect of gNO inhalation may be similar to that observed after administration of solutions of dinitrosyl iron complexes, namely, to the presence of dinitrosyl iron complexes with thiol-containing ligands in lung and airway tissues. With regard to the hypothesis posited earlier that these complexes can suppress coronavirus replication as donors of nitrosonium cations (Biophysics 65, 818, 2020), it is not inconceivable that administration of gNO or chemically synthesized dinitrosyl iron complexes with thiol-containing ligands may help treat COVID-19. In tests on the authors of this paper as volunteers, the tolerance concentration of gNO inhaled within 15 min was approximately 2000 ppm. In tests on rats that inhaled sprayed aqueous solutions of dinitrosyl iron complexes, their tolerance dose was approximately 0.4 mmol/kg body weight.

We studied the effect of dinitrosyl-iron complexes with N-acetyl-L-cysteine as a thiol-containing ligand (DNIC-Acc) after transdermal administration to rats. Electron paramagnetic resonance spectroscopy with a lipophilic NO spin trap (a complex of iron and diethyldithiocarbamate ions) showed that DNIC-Acc administration significantly increased the total level of NO in the lung and liver tissues of the animal, which was accompanied by a slight decrease in the mean BP (

—The effect of injected intravenously dinitrosyl iron complexes with glutathione ligand on the structural and conformational characteristics of albumin, which is a primary ligand of these complexes in plasma, and on molecules of the lipid phase in the erythrocyte membrane, which constitute the microenvironment of dinitrosyl iron complexes in erythrocytes, was analyzed. The analysis of EPR spectra of 5- and 16-DOXYL stearic acid spin probes in plasma and erythrocyte suspensions before and after injection of dinitrosyl iron complexes with glutathione was performed in the experiments. It has been found that injection of these complexes into an organism does not affect the molecular motion in albumin hydrophobic regions in plasma and erythrocyte membranes, while at the same time they stimulate incorporation of charged spin labels into the erythrocyte membrane. Apparently, this was due to a change in the charge on the outer surface of the erythrocytes.

—The objective of this work was to study the biological effect of dinitrosyl iron complexes (DNICs) with the glutathione ligand (GSH−DNICs) as a stabilized form of nitric oxide in a rat model of nitric oxide hyperproduction induced by inflammation. Administration of GSH−DNICs in endotoxin shock did not increase the total nitric oxide levels in rat organs, but exerted a protective effect by suppressing nitric oxide hyperproduction in the liver and led to an accumulation of the complexes with protein ligands in the kidney.

Subcutaneous injection of Oxacom with glutathione-bound dinitrosyl iron complex as the active principle produced a slower drop of mean BP and longer accumulation of protein-bound dinitrosyl iron complexes in whole blood and tissues than intravenous injection of this drug, while durations of hypotensive effect in both cases were practically identical. In contrast to intravenous injection of the drug, its subcutaneous administration was not characterized by a high concentration of protein-bound dinitrosyl iron complexes in the blood at the onset of experiment; in addition, accumulation of these NO forms in the lungs was more pronounced after subcutaneous injection than after intravenous one.