ABSTRACT
A comparative evaluation of the antiviral activity of a number of new and previously synthesized terpenophenols and their N- or O-containing derivatives against the A/Puerto Rico/8/34 (H1N1) virus strain was carried out. 2-Isobornylphenol, 1,2-dihydroxy-6-isobornyl-4-methylbenzene, 2-isobornyl-1,4-benzoquinone, and N-butyl-4-hydroxy-3,5-diisobornylbenzamide showed the highest activity.
ABSTRACT
We studied the effect of antioxidants dibornol (2,6-diisobornyl-4-methylphenol) and its derivative (4-hydroxymethyl-2,6-diisobornylphenol), members of the alkylated phenols group, on the redox potential of male germ cells and their morphological and functional state in the rat model of pathospermia. Pharmacological effect was observed in animals treated with dibornol. The studied compounds led to the normalization of the antioxidant-prooxidant balance. However, the value of this indicator against the background of treatment with dibornol derivative attested to a shift in the redox balance of cells towards reduction reactions.
Subject(s)
Antioxidants , Phenols , Male , Animals , Rats , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/metabolism , Reactive Oxygen Species , Oxidation-Reduction , Phenols/pharmacology , Phenols/therapeutic use , Germ Cells/metabolismABSTRACT
2,6-Diisobornyl-4-methylphenol (Dibornol, 10 mg/kg intragastrically daily for 5 days after myocardial ischemia/reperfusion) 1.5-fold increased rat survival during the acute post-infarction period in comparison with the control group. In survivors, Dibornol reliably prevented post-ischemic progression of heart failure in the delayed post-infarction period (30 days after ischemia/reperfusion), which was seen from an increase in the left-ventricular developed pressure by 22%, left-ventricular contractility index by 19%, and +dP/dt by 34%. Left-ventricular end-diastolic pressure was by 39% lower than in control animals. Morphological study of heart sections from control group animals showed that Dibornol reduced the area of post-ischemic myocardial damage in the delayed period after ischemia/reperfusion to 3±1% (vs 18±2% in the control group).
Subject(s)
Cresols/therapeutic use , Heart Ventricles/drug effects , Myocardial Reperfusion Injury/drug therapy , Animals , Blood Pressure/drug effects , Cresols/chemistry , Heart/drug effects , Heart Ventricles/metabolism , Male , Myocardial Reperfusion , Myocardial Reperfusion Injury/metabolism , RatsABSTRACT
Experimental model of sulpiride-provoked benign prostatic hyperplasia was employed to comparatively assess the effect of phenolic antioxidants (dihydroquercetin, p-thyrozol, dibornol, and prostagenin) on prostate morphology. All examined agents decreased the degree of hyperplasia in acinar epithelium; the greatest efficacy was demonstrated by prostagenin. Moreover, dihydroquercetin and p-thyrozol increased the cross-section area of acinar lumina and prostate volume, which is inadmissible in this pathology. These results suggest that the use of phenolic antioxidants in the therapy of benign prostatic hyperplasia should be strictly controlled.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Methimazole/pharmacology , Phenols/pharmacology , Prostatic Hyperplasia/drug therapy , Quercetin/analogs & derivatives , Acinar Cells/drug effects , Acinar Cells/pathology , Animals , Animals, Outbred Strains , Disease Models, Animal , Humans , Male , Organ Size/drug effects , Prostate/drug effects , Prostate/pathology , Prostatic Hyperplasia/chemically induced , Prostatic Hyperplasia/pathology , Quercetin/pharmacology , Rats , Sulpiride/administration & dosageABSTRACT
Neuroprotective activity of 2,6-diisobornyl-4-methylphenol (Dibornol) was studied under conditions of experimental focal cerebral ischemia/reperfusion modeled by intraluminal occlusion of the left middle cerebral artery for 1 h followed by recirculation. Dibornol administered in a dose of 10 mg/kg intragastrically 24 h and 30 min before and 24 h after focal ischemia/reperfusion modeling reduced the size of the brain infarction zone by 52% (48 h after recirculation) and neurological deficit by 1.7-2.4 times in comparison with that in control animals.
Subject(s)
Brain Ischemia/drug therapy , Neuroprotective Agents/therapeutic use , Animals , Brain/drug effects , Brain/pathology , Brain Infarction/drug therapy , Camphanes/therapeutic use , Cresols/therapeutic use , Male , Rats , Rats, Wistar , Reperfusion Injury/drug therapyABSTRACT
We studied the effect of O-((((4-hydroxy-3,5-di(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl) benzyl)oxy)ethyl)-O-(2-hydroxyethyl)-(1â4)-α-D-glucan (D-HES, 80 mg/kg, intravenously) and reference preparation ethylmethylhydroxypyridine succinate (EMHP-S, 50 mg/kg, intravenously) on rat survival and neurological deficit in 24 h after transient global cerebral ischemia in Wistar rats. Intravenous administration of D-HES and EMHP-S significantly increased the number of survivors by 68 and 78%, respectively, in comparison with the control group. In groups treated with D-HES and EMHP-S, the number of animals with severe neurological deficit was significantly lower and the number of animals moderate or mild neurological deficit was significantly higher than in the control group.
Subject(s)
Brain Ischemia/drug therapy , Hydroxyethyl Starch Derivatives/administration & dosage , Ischemic Attack, Transient/drug therapy , Neuroprotective Agents/administration & dosage , Pyridines/administration & dosage , Administration, Intravenous , Animals , Drug Evaluation, Preclinical , Infusions, Intravenous , Male , Nervous System Diseases/therapy , Rats , Rats, Sprague-Dawley , Rats, WistarABSTRACT
We studied the cardioprotective effect of 2,6-diisobornyl-4-methylphenol under conditions of myocardial ischemia/reperfusion in rats. Daily administration of 2,6-diisobornyl-4-methylphenol (100 mg/kg intragastrically) over 3 days before and 5 days after modeling of myocardial ischemia/reperfusion prevented the increase in the infarction area by almost 2 times in comparison with the control by day 5 after recirculation. The type and severity of pathological changes in ECG parameters reflecting necrotic changes in the myocardium under the action of the compound significantly decreased by day 35 of the experiment. Animal survival rate during the first 24 h after ischemia/reperfusion modeling in the experimental group was by 29% higher than in the control group.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Antioxidants/pharmacology , Boron Compounds/pharmacology , Cardiotonic Agents/pharmacology , Cresols/pharmacology , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Animals , Anti-Arrhythmia Agents/chemical synthesis , Antioxidants/chemical synthesis , Boron Compounds/chemical synthesis , Cardiotonic Agents/chemical synthesis , Coronary Occlusion/drug therapy , Coronary Occlusion/mortality , Coronary Occlusion/physiopathology , Coronary Vessels/surgery , Cresols/chemical synthesis , Drug Administration Schedule , Gastric Absorption , Heart Rate/drug effects , Male , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/mortality , Myocardial Reperfusion Injury/physiopathology , Rats , Rats, Wistar , Survival AnalysisABSTRACT
We compared bioavailability of 4-methyl-2,6-diisobornylphenol after single intragastric administration to rats in a dose of 200 mg/kg in starch suspension and in almond oil. Absorption of 4-methyl-2,6-diisobornylphenol in the gastrointestinal tract after administration in almond oil was much more efficient than after administration in aqueous starch mucus.
Subject(s)
Antioxidants/administration & dosage , Antioxidants/pharmacokinetics , Camphanes/administration & dosage , Camphanes/pharmacokinetics , Cresols/administration & dosage , Cresols/pharmacokinetics , Phenols/administration & dosage , Phenols/pharmacokinetics , Administration, Oral , Animals , Gastrointestinal Tract/metabolism , Intestinal Absorption/drug effects , Male , Plant Oils/chemistry , Rats , Rats, WistarABSTRACT
We studied the effects of novel sterically hindered phenol, 4-methyl-2,6-diisobornyl phenol (dibornol) on the rheological properties of the blood in the model of myocardial ischemia/reperfusion. Dibornol (100 mg/kg intraperitoneally for 3 days before and 5 days after ischemia/reperfusion) decreased blood viscosity by 9-25% in comparison with that in sham-operatedanimals by modulating cellular (erythrocyte deformability and aggregation) and plasma (plasma viscosity) rheological parameters. Normalization of blood rheology under the influence of dibornol increased the availability of oxygen to tissues at high shear rates by 9-18% after acute ischemia/reperfusion in rats.
Subject(s)
Camphanes/pharmacology , Camphanes/therapeutic use , Cresols/pharmacology , Cresols/therapeutic use , Myocardial Ischemia/drug therapy , Animals , Blood Viscosity/drug effects , Erythrocyte Deformability/drug effects , Male , Rats , Rats, WistarABSTRACT
A series of water-soluble conjugates has been synthesized from polyethylene glycols of various lengths and 4-bromomethyl-2,6-diisobornylphenol. Evaluation of membrane protective and antioxidant activity of synthesized products on the model of H2O2-induced hemolysis of blood erythrocytes showed that conjugates have considerable antioxidant activity. A significant membrane protective effect was showed in conjugates with 0.2 and 0.8 mass. % of 2,6-diisobornyl-4-methylene fragments.
