ABSTRACT
In vivo effect of isothiourea derivatives on NO production was studied by the method of electron paramagnetic resonance spectroscopy with a spin trap. We evaluated the influence of these compounds on hemodynamic parameters in anesthetized rats with hypovolemic shock. A correlation was found between the size of S,N-substituents in isothiourea derivatives (methyl, ethyl, and isopropyl) and NO inhibitory activity of compounds. The antihypotensive effect was more pronounced in compounds with high NO inhibitory activity containing the isopropyl radical.
Subject(s)
Antihypertensive Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Hypotension/drug therapy , Hypotension/etiology , Shock/complications , Thiourea/therapeutic use , Animals , Antihypertensive Agents/chemistry , Electron Spin Resonance Spectroscopy , Enzyme Inhibitors/chemistry , Hemodynamics/drug effects , Male , Nitric Oxide Synthase/antagonists & inhibitors , Rats , Rats, Wistar , Thiourea/chemistryABSTRACT
The effect of radioprotectors of different structure on the syntheses of nitric oxide induced by endotoxin in mice was studied. Using ESR-spectroscopy and spin trap techniques, it was shown that compounds of different chemical structure, such as aminothiols, isothiuronium derivatives, thiazolines, indolylalkylamines and others, suppressed the nitric oxide production in a whole body. The analysis of the relevant literature has confirmed the phenomenon described by the authors: radioprotectors show NO-inhibiting activity.
Subject(s)
Nitric Oxide/antagonists & inhibitors , Radiation-Protective Agents/pharmacology , Animals , Cysteine/pharmacology , Data Interpretation, Statistical , Electron Spin Resonance Spectroscopy , Endotoxins , Liver/metabolism , Male , Mercaptoethylamines/pharmacology , Mice , Nitric Oxide/biosynthesis , Organothiophosphates/pharmacology , Radiation-Protective Agents/administration & dosage , Spin TrappingABSTRACT
Using the method of electron paramagnetic spectroscopy we demonstrated that thiazine-thiazoline compounds and aminoethyl isothiourea containing the thioamidine group inhibit NO production in the liver of endotoxin-treated mice. Injection of these agents to anesthetized rats increased arterial pressure and enhanced respiration rate. This effect probably reflects inhibition of not only inducible, but also the constitutive synthesis of NO by compounds with thioamidine group.
Subject(s)
Enzyme Inhibitors/pharmacology , Nitric Oxide/antagonists & inhibitors , Thiazines/pharmacology , Thiazoles/pharmacology , Vasoconstrictor Agents/pharmacology , Animals , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Endotoxins , Liver/drug effects , Liver/enzymology , Male , Mice , Nitric Oxide Synthase/antagonists & inhibitors , Rats , Rats, Wistar , Respiration/drug effects , Species SpecificityABSTRACT
It was shown that gas hypoxic mixture containing O2 (10%) and N2 (90%) significantly decreases "intestinal" death of Wistar rats on the 5th day following irradiation and normalizes Na+,K+-ATPase activity of the small intestine mucosa plasma membranes.
Subject(s)
Intestinal Mucosa/radiation effects , Intestine, Small/radiation effects , Oxygen/pharmacology , Radiation Injuries, Experimental/mortality , Radiation Tolerance , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Cell Membrane/enzymology , Enzyme Activation/drug effects , Enzyme Activation/radiation effects , Intestinal Mucosa/enzymology , Intestine, Small/enzymology , Male , Radiation Injuries, Experimental/enzymology , Radiation Injuries, Experimental/prevention & control , Rats , Rats, Inbred Strains , Time FactorsABSTRACT
In experiments on 128 dogs (males and females) weighing 7-24 kg it was demonstrated that inhalation of gas hypoxic mixture containing O2 (10%) and N2 (90%) decreased significantly the level of PO2 in radiosensitive tissues and exerted a radioprotective effect on the exposed animals (60Co, doses of 2.8, 3.5-3.8 and 4.2 Gy, DMF = 1.3). At a dose of 8 Gy the average life of animals increased from 6.2 +/- 0.8 days (control) up to 9.3 +/- 1.1 days after the application of GHM -10.
Subject(s)
Nitrogen/pharmacology , Oxygen/pharmacology , Radiation Injuries, Experimental/drug therapy , Radiation-Protective Agents , Animals , Cobalt Radioisotopes/administration & dosage , Dogs , Dose-Response Relationship, Radiation , Female , Male , Oxygen/analysis , Partial Pressure , Phosphorus/analysisABSTRACT
Gas hypoxic mixture (GHM-10) decreased significantly the occurrence and duration of radioepidermitis after local therapeutic fractionated irradiation of Wistar rat skin with a cumulative dose of 66 Gy. In patients subjected to radiation therapy and protected with GHM-10 erythema and epidermitis developed at a much higher cumulative dose than in the controls. With erythema dose modifying coefficient was 1.38 +/- 0.06.
Subject(s)
Hypoxia/physiopathology , Nitrogen/administration & dosage , Oxygen/administration & dosage , Radiation-Protective Agents/administration & dosage , Skin/radiation effects , Animals , Drug Evaluation , Drug Evaluation, Preclinical , Erythema/prevention & control , Humans , Male , Oxygen Consumption/radiation effects , Partial Pressure , Radiation Injuries, Experimental/prevention & control , Radiodermatitis/prevention & control , Rats , Rats, Inbred StrainsABSTRACT
In experiments on 1152 CBA mice and SHK colony and on 1180 Wistar rats it was demonstrated that a gas hypoxic mixture containing oxygen (10%) and nitrogen (90%) (GHM-10) reduced the intestinal syndrome of the acute radiation sickness in animals exposed to ionizing radiation at rest, during physical exercises, after radiation sickness endured earlier, after exposure to SHF, after fractionated irradiation, and after radiation-and-thermal damage.
