ABSTRACT
Fluorescence resonance energy transfer study revealed decreased intermonomer mobility of Ca-actin and Mg-actin filaments of myocardial myofibrils in myocardial dystrophy caused by diffuse endocrine disorders, e. g. hypothyrosis. Cis374 axial distance in Ca-actin filament protomer increased in hypothyrosis. Intracellular pH has no effect on inter-monomer mobility of Ca-actin filament.
Subject(s)
Actins/chemistry , Actins/physiology , Hypothyroidism/physiopathology , Myocardium/metabolism , Actins/metabolism , Animals , Female , Hypothyroidism/metabolism , Male , Naphthalenesulfonates , RatsABSTRACT
The development of severe heart failure associated with toxicoallergic myocarditis is accompanied by profound structural and conformational changes in the outer domain of actin (major protein in a thin filament of cardiomyocyte sarcomere). These changes were revealed in subdomains 1 (Cys374 and Cys10) and 2 (Lys61 and Tyr69). Structural and conformational changes in the monomer and protomer of the actin thread during heart failure were energetically forbidden. Variations in the distance between amino acid residues exceeded 0.26 nm. They were partly or completely reversible in vivo under the influence of cardiotropic drug refracterin with high antihypoxic activity, as well as in vitro after treatment with digitalis preparations optimizing the concentration of ATP.
Subject(s)
Cardiac Glycosides/chemistry , Heart Diseases/pathology , Muscles/pathology , Myofibrils/pathology , Acetyldigoxins/pharmacology , Animals , Heart Diseases/metabolism , In Vitro Techniques , Molecular Conformation , Muscle Contraction , Myocardial Contraction , Myocardial Ischemia/pathology , Myocarditis/pathology , Myofibrils/metabolism , RabbitsABSTRACT
Experimental skin ischemia in rats was induced by suturing a skin fold on the back with a silk thread. Combined pretreatment with superoxide dismutase (intraperitoneally) and Reamberin (intravenously) in doses of 0.01 and 6.25 mg/kg (by succinate concentration), respectively, produced a strong protective effect on the skin. The index of cytolysis decreased by 39%. The more pronounced antinecrotic effect of combined treatment with superoxide dismutase and Reamberin compared to the effect of Reamberin alone was related to a sharp increase in the reserve capacity of the antioxidant system. After combined therapy, activity of antioxidant defense enzymes not only increased, but even exceeded the normal level. The increase in activity of endogenous superoxide dismutase under the influence of combined therapy was accompanied by suppression of superoxide anion production.
Subject(s)
Antioxidants/therapeutic use , Ischemia/drug therapy , Skin/blood supply , Skin/drug effects , Superoxide Dismutase/pharmacology , Adenosine Diphosphate/analysis , Adenosine Triphosphate/analysis , Animals , Antioxidants/administration & dosage , Antioxidants/pharmacology , Dose-Response Relationship, Drug , Drug Therapy, Combination , Injections, Intraperitoneal , Ischemia/enzymology , Ischemia/etiology , Ischemia/pathology , Male , Necrosis/drug therapy , Random Allocation , Rats , Rats, Inbred Strains , Skin/enzymology , Superoxide Dismutase/administration & dosage , Superoxide Dismutase/metabolism , Superoxides/antagonists & inhibitorsABSTRACT
Antinecrotic activity of SOD was studied in rats with experimental skin ischemia. Treatment with SOD increased activity of endogenous SOD in skin homogenates (by 70 and 26% compared to the ischemic and intact skin, respectively). However, the rate of superoxide anion generation remained unchanged after SOD treatment. Creatine phosphate content and NAD/NADH redox potential increased by 16 and 21%, respectively, on day 3 after SOD administration. The increase in functional activity of the energy supply system and rise in the reserve capacity of the antioxidant protection system contribute to inhibition of lactate dehydrogenase and creatine phosphokinase and decrease in the cytolysis index under the influence of SOD. Our results indicate that SOD produces the antinecrotic effect and holds much promise for the therapy of skin ischemia.
Subject(s)
Antioxidants/pharmacology , Ischemia/prevention & control , Skin/blood supply , Superoxide Dismutase/pharmacology , Alanine Transaminase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Creatine Kinase/antagonists & inhibitors , Ischemia/pathology , L-Lactate Dehydrogenase/antagonists & inhibitors , Male , Necrosis/prevention & control , Rats , Skin/drug effects , Skin/enzymology , Superoxide Dismutase/metabolismABSTRACT
Fetal growth retardation, hypercoagulation, and changes in pulmonary fibrinolytic activity were observed during experimental gestosis induced by long-term feeding of a high-sodium diet. The course of fraxiparine treatment to correct gestosis improved hemostasis-regulating lung function, decreased coagulation activity of the arterial blood, and increased the weights of the placenta and fetus.
Subject(s)
Anticoagulants/pharmacology , Hemostasis/drug effects , Lung/physiopathology , Nadroparin/pharmacology , Pre-Eclampsia/blood , Animals , Birth Weight/drug effects , Blood Coagulation , Blood Coagulation Disorders/therapy , Female , Fetal Growth Retardation/etiology , Fetus/drug effects , Fibrinogen/analysis , Fibrinogen/drug effects , Placenta/drug effects , Pre-Eclampsia/etiology , Pre-Eclampsia/therapy , Pregnancy , Random Allocation , RatsABSTRACT
Structural and conformational changes in myocardial and erythrocyte actin during cardiac ischemia were studied by the method of fluorescence resonance energy transfer with highly selective fluorescent probes. In contrast to 15-min coronary artery occlusion, 120-min ischemia was accompanied by irreversible structural and conformational changes in the small domain of erythrocyte actin. Posttranslational changes during myocardial ischemia concerned the N- and C-terminal regions of actin and went beyond the allowed conformational fluctuations in the actin molecule without breaking the energy barrier. Our results suggest that under conditions of ischemia, actin of the myocardium and erythrocyte cytoskeleton loses its ability to acquire conformation required for force generation by cardiomyocyte myofibrils and maintenance of elasticity and integrity of the erythrocyte membrane.
Subject(s)
Actins/chemistry , Erythrocytes/metabolism , Myocardial Ischemia/pathology , Myocardium/metabolism , Animals , Coronary Vessels/pathology , Cytoskeleton/metabolism , Dogs , Fluorescence Resonance Energy Transfer/methods , Hydrogen-Ion Concentration , Ischemia/pathology , Myocardium/chemistry , NAD/chemistry , Protein Conformation , Protein Structure, Tertiary , Pyridines/chemistry , Time FactorsABSTRACT
Reamberin in a dose of 25 mg/kg (succinate concentration) was injected intravenously for 3 days starting from the 1st hour after skin ischemia modeling. This treatment decreased activities of lactate dehydrogenase, aspartate transaminase, and creatine phosphokinase in skin homogenates by 1.6 times, 19%, and 51.3%, respectively. The index of cytolysis decreased by 18%. Reamberin had an energotropic effect, which manifested in an increase in the total ATP content and concentration of creatine phosphate (by 16 and 10%, respectively). After administration of Reamberin, activity of the succinate-ubiquinone reductase system increased by 17%. Under these conditions succinate dehydrogenase activity exceeded the normal by 21%. Reamberin had no effect on the mitochondrial NADH-ubiquinone reductase system in dermal cells during skin ischemia. Superoxide dismutase activity in the area of necrosis increased to the control level on day 3 of treatment with Reamberin. Activities of catalase and glutathione peroxidase increased by 13 and 19%, respectively. Our results indicate that the course of intravenous treatment with Reamberin for 3 days contributes to an increase in reserve capacities of the antioxidant protection system and produces a protective effect during skin ischemia.
