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1.
Biomed Khim ; 65(3): 231-238, 2019 Apr.
Article in Russian | MEDLINE | ID: mdl-31258147

ABSTRACT

The goal of this study was to examine effects of a novel galanin receptor agonist GalR1-3 [bAla14, His15]-galanine 2-15 (G), obtained by automatic solid-phase synthesis, on the metabolic state of the area at risk and the size of acute myocardial infarction (MI) in rats in vivo and evaluate its toxicity in BALB /c mice. In anesthetized rats, regional ischemia was simulated by coronary artery occlusion and then coronary blood flow was restored. The peptide G was administered intravenously (i.v.) with a bolus after a period of regional ischemia in the dose range of 0.25-3.0 mg/kg. The sizes of MI and the activities of creatine kinase-MB (СK-MB) and lactate dehydrogenase (LDH) in blood plasma were estimated. The effect of administration of the optimal dose of G (1.0 mg/kg) on myocardial content of adenine nucleotides (AN), phosphocreatine (PCr), creatine (Cr) and lactate was studied. I.v. administration of G to rats at a dose of 1.0 mg/kg slightly affected hemodynamic parameters, but reduced MI size by 40% and decreased plasma LDH and CK-MB activity by the end of reperfusion compared to control. These effects were accompanied by a significant improvement in energy state of area at risk (AAR) - an increase in myocardial content of ATP, åAN, PCr and åCr, and combined with a decrease in myocardial lactate level compared with the control. Toxicity of peptide G was studied with a single intraperitoneal injection of 0.5-3.0% solution of the peptide substance to mice. The absence of signs of intoxication and death of animals after G injection in the maximum possible dose did not allow determining the value of the average lethal dose. The results indicate therapeutic potential of the peptide G for preventing myocardial ischemia and reperfusion injury and feasibility for further study of its pharmacological properties and mechanisms of action.


Subject(s)
Myocardial Infarction/pathology , Peptides/pharmacology , Receptors, Galanin/agonists , Animals , Creatine Kinase, MB Form/blood , Disease Models, Animal , L-Lactate Dehydrogenase/blood , Mice , Mice, Inbred BALB C , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/pathology , Rats
2.
Anesteziol Reanimatol ; (3): 71-2, 2002.
Article in Russian | MEDLINE | ID: mdl-12221885

ABSTRACT

Experimental studies on mice showed that after four 30-min and 60-min inhalations of Xe:O2 (80:20) during 2 weeks, weight indexes of the lymphoid organs (spleen and thymus) increased, phagocytic activity did not change, and primary immune response was moderately stimulated. This indicates that xenon exerted no immunotoxic effects and can be used in patients with diseases associated with primary immunodeficiency. Study of allergic effects on albino guinea pigs showed that on days 14 and 21 of sensitization xenon in the resolving dose possessed no anaphylactogenic activity, caused no specific lysis of leukocytes, and did not modulate the counts of basophils and eosinophils. Xenon did not induce allergic reactions and is not a potential allergen, which is important in patients with panallergy.


Subject(s)
Anesthetics, Inhalation/toxicity , Xenon/toxicity , Administration, Inhalation , Animals , Antibody Formation/drug effects , Guinea Pigs , Leukocytes/immunology , Male , Mice , Mice, Inbred CBA , Organ Size , Phagocytosis/immunology , Spleen/anatomy & histology , Spleen/immunology , Thymus Gland/anatomy & histology , Thymus Gland/immunology
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