ABSTRACT
Methods of fluorescent probing, spectrophotometry and microcalorimetry were applied to investigate the alterations in biophysical parameters of erythrocytes membranes, and specifically microviscosity, surface charge, molecular organization of lipid bilayer and lipid-protein interactions under conditions of acute pain syndrome produced by experimental chemical lesion. The distinctive features of non-opiod analgesics interactions and binding to the erythrocytes membranes of rats subjected to acute nociceptive pain accompanied with oxidative stress development were investigated. The abilities of analgesics under research, and namely paracetamol, aspirin, phenazone, ketorolac, pyrodazole, ketoprofenum, natrium mefenaminate, indometacin, nimesulide to make up physico-chemical complexes with lipoperoxidation modified erythrocytes surface and protein-lipid bilayer showed marked changes. The significance of oxidative damage of biophase under conditions of acute pain syndrome for analgesics effective pharmacodynamics and pharmacokinetics realization is under consideration.
Subject(s)
Acute Pain/prevention & control , Analgesics, Non-Narcotic/metabolism , Erythrocyte Membrane/metabolism , Lipid Bilayers/metabolism , Acetaminophen/metabolism , Acetaminophen/pharmacology , Analgesics, Non-Narcotic/pharmacology , Animals , Antipyrine/metabolism , Antipyrine/pharmacology , Aspirin/metabolism , Aspirin/pharmacology , Calorimetry , Cell Fractionation , Erythrocyte Membrane/chemistry , Fluorescent Dyes , Indomethacin/metabolism , Indomethacin/pharmacology , Ketoprofen/metabolism , Ketoprofen/pharmacology , Ketorolac/metabolism , Ketorolac/pharmacology , Lipid Bilayers/chemistry , Lipid Peroxidation/drug effects , Male , Orphenadrine/metabolism , Orphenadrine/pharmacology , Pain Measurement , Rats , Spectrometry, Fluorescence , Sulfonamides/metabolism , Sulfonamides/pharmacologyABSTRACT
Energy and structural parameters of monochromanes and trimethylphenols derivatives have been chracterized through the employment of semiempirical methods of quantum chemistry. The correlation has been proved between antiradical, hepatoprotective properties of these compounds and energy and structural of their molecules that confirms the presence of relation between structure activity and electron-donor properties of the investigated monochromanes and trimethylphenols.
Subject(s)
Antioxidants/pharmacology , Chromans/pharmacology , Liver/drug effects , Models, Chemical , Phenols/pharmacology , Quantum Theory , Animals , Antioxidants/chemistry , Chemical Phenomena , Chromans/chemistry , Electron Transport , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Intracellular Membranes/drug effects , Intracellular Membranes/metabolism , Lipid Peroxidation/drug effects , Liver/metabolism , Phenols/chemistry , Rats , Structure-Activity RelationshipABSTRACT
Using biochemical and physicochemical methods of investigation in vivo, the effect of the substance NC-224, N-, S-chinasolone-derivative, on the lipoperoxidation activity in rat liver endoplasmatic reticulum membranes and nuclear chromatin fractions under tetrachloromethane intoxication have been studied. It was shown that NC-224 has pronounced antioxidant activity which is the biochemical basis of the substance membrane- and genome-protective effects and its ability to restore physicochemical properties of the surface and hydrophobic zones of hepatocyte membranes and structural parameter nuclear chromatin fractions in the conditions of chemical liver injury.
Subject(s)
Chromatin/drug effects , Endoplasmic Reticulum/drug effects , Lipids/analysis , Malondialdehyde/analysis , Oxyquinoline , Animals , Antioxidants/pharmacology , Butylated Hydroxytoluene/pharmacology , Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Chromatin/metabolism , Endoplasmic Reticulum/metabolism , Hepatocytes/drug effects , Hepatocytes/pathology , Lipid Peroxidation/drug effects , Lipids/chemistry , Liver/cytology , Liver/drug effects , Liver/pathology , Oxyquinoline/analogs & derivatives , Oxyquinoline/pharmacology , Rats , Rats, WistarABSTRACT
Using some biochemical and physico-chemical methods of investigation, antioxidant activity and membrane protective effect of derivatives of monochromanes and trimethylphenols has been studied most active inhibitors of lipoperoxidation and the compounds capacity to structural modification of properties of the surface and hydrophobic zones of phospholipids bilayer in membranes of endoplasmic reticulum of the liver cells of rats have been determined.
