[Distribution of 4-methyl-2,6-diisobornylphenol in rat tissues].

We have studied the distribution of the new compound 4-methyl-2,6-diisobornylphenol in rats after a single oral administration in a dose of 20 mg/kg. The pharmacokinetic parameters have been estimated by the noncompartmental method. It is established that the drug is nonuniformly distributed in the body and has a high affinity for liver and heart. A low penetration of 4-methyl-2,6-diisobornilphenol has been found in brain tissue. The accumulation of 4-methyl-2,6-diisobornilphenol in adipose tissues has not been found. It been showed that the drug is slowly eliminated from the body, especially from the heart tissues for which the mean retention time is MRT = 45 h.

[Evaluation of the linearity of pharmacokinetics of the phenolic antioxidant 4-methyl-2,6-diisobornylphenol upon intragastric administration].

The linearity of pharmacokinetics of 4-methyl-2,6-diisobornylphenol after single intragastric administration in doses within 10 - 200 mg/kg has been studied in rats. It has been established that pharmacokinetics of 4-methyl-2,6-diisobornilphenol in the indicated dose range is not linear due to a limited absorption of the drug from the intestine.

[Pharmacokinetics of phenolic antioxidant 4-methyl-2,6-diisobornylphenol upon intravenous injection].

The pharmacokinetics of 4-methyl-2,6-diisobornylphenol (MDIBP) in rat blood plasma has been studied after intravenous injection. The drug concentration in the plasma was determined using a reverse-phase HPLC procedure. It is shown that MDIBP rapidly penetrates into intensively perfused organs, but is slowly eliminated from the organism (MRT value amounting to 9 h).

[Main pharmacokinetic parameters of p-tyrosol after intravenous injection in rats. Part III: Distribution of p-tyrosol in rat].

Distribution of p-tyrosol in organism was studied in rats after a single intravenous administration in a dose of 200 mg/kg. It was shown that p-tyrosol rapidly penetrates into well perfused organs (brain, heart, kidneys). The maximum concentration ofp-tyrosol in these organs was determined in 1 minute after administration, and the mean distribution constant was within 0.8-1.11. The albumin bound fraction ofp-tyrozol amounted to 0.26-0.30.

[Structural changes of eye chorioretinal complex after total cerebral ischemia and their correction].

Structural changes of eye chorioretinal complex were investigated in 40 adult male outbred albino rats after total transient cerebral ischemia using electron microscopy and morphometric analysis. Furthermore, the influence of a new sterically hindered phenolic antioxidant dibornol on these processes was estimated. Our studies demonstrated that total transient cerebral ischemia in rats resulted in the capillary thrombosis of the choriocapillary lamina of the uvea, structural disturbances of the blood-retinal barrier, degeneration of the retinal neurons and radial glia. Course administration of dibornol was shown to improve the microcirculation and to protect the retinal neuronal structures, pigment epithelium, and radial glia.

[Hepatoprotective effect of thiophane in rats with experimental carbon tetrachloride-induced hepatitis].

A hepatoprotective effect of thiophan was studied on the model of carbon tetrachloride-induced hepatitis in rats. Therapeutic administration of thiophan repairs the antitoxic function of liver, normalizes cytolysis marker activity, and improves the synthetic function of liver and the carbohydrate and lipid metabolism. The hepatoprotective activity of thiophan is similar to effect of silimarin.

[Hemorheological effects of thiophane on tetrachloromethane induced hepatic damage].

Carbon tetrachloride-induced hepatitis in rats is accompanied by blood hyperviscosity syndrome development. A course intragastric administration of thiophane under these conditions prevents the increase in whole blood viscosity by normalizing the microrheological indices (deformability and aggregation of erythrocytes), which is manifested by increasing oxygen availability for tissues.

[Antioxidant and cardioprotective effects of N-tyrosol in myocardial ischemia with reperfusion in rats].

We demonstrated in experiments on rats with left coronary artery occlusion that intravenous administration of 20 mg/kg n-tyrosol during ischemia limited manifestations of oxidative stress in myocardial tissue during early post reperfusion period: content of diene and triene conjugates lowered 16 and 20%, respectively. This was associated with higher preservation of cardiomyocytes and reduction of the infarction zone.

[Neuroprotective effects of dibornol and mechanism of its action in rats with cerebral ischemia].

Neuroprotective activity of the new sterically hindered phenolic antioxidant 4-methyl-2,6-diisobornylphenol (dibornol) in rats with total transient cerebral ischemia was investigated. Dibornol decreased mortality of rats and the number of animals with severe neurological deficit; moreover, it accelerated restoration of neurological status in the survived rats. Neuroprotective activity of dibornol is based on its ability to diminish lipid peroxidation in ischemic brain, suppress cerebral tissue hypoxia and protect functional activity of endothelium. Improved oxygen delivery was a consequence of reduced hyperviscosity syndrome (enhanced deformability of erythrocytes and their decreased aggregation).

[Morphological changes in retinal neurons in rats with streptozotocin diabetes and their correction by O-isobornylphenol derivative].

Along with microangiopathy, degeneration of retinal neurons is one of the basic causes of blindness in patients with diabetic retinopathy. Using the electronic microscopy and morphometric analysis, the structural changes of neurosensory cells, associative and ganglionic retinal neurons were studied in 30 albino outbred male rats with long term (2 months) streptozotocin diabetes and the effect of a new semisynthetic antioxidant belonging to a group of strictly hindered phenols (4-methyl-2,6-diisobornylphenol) on these parameters was evaluated. In diabetic rats, the destructive changes of external segments of neurosensory cells and ganglionic retinal neurons were found. The numerical density of neurosensory and ganglionic cells was reduced, while the proportion of these cells with pyknotic nuclei was increased. 4-Methyl-2,6-diisobornylphenol demonstrated neuroprotective effect by preventing destructive changes of neurosensory cells and ganglionic retinal neurons.

[Therapeutic effect of p-tyrosol on myocardial electric instability induced by coronary occlusion].

In experiments on rats with left coronary artery occlusion, p-tyrosol (20 mg/kg, intravenously) showed the ability to decrease myocardial electric instability in phase 1b of ventricular arrhythmias: a fraction of rats without arrhythmia was increased by 36%, and the mean value of ventricular arrhythmia index exhibited a 3-fold decrease.

[Antiedematous effect of polyosm in rats with freezing lesion of brain].

Effect of the intravenous injection of polyosm (30% solution of polyethylene oxide with a molecular mass of 400, PEO-400) was investigated on Wistar rats with a model of brain edema induced by a freezing lesion in one cerebral hemisphere. The brain edema development was estimated by measuring the active resistance of tissues in the right and left parietal cortex and the content of water in both hemispheres. A course of the intravenous injections of polyosm (1 g/kg of PEO-400 daily during 3 days) after the model lesion onset decreased the initially elevated active resistance in the edematous cerebral tissue and reduced water accumulation in the damaged hemisphere.

[Polyethox corrects hemodynamic and hemorrheological disturbances after infusion-transfusion therapy of massive hemorrhage].

Inclusion of polyethox, a medicinal form of high-molecular (4,5 x 10(6) Da) poly(ethylene oxide), into infusion-transfusion therapy of massive hemorrhage (33% of blood volume) in cats leads to an increase in the stroke and cardiac indices, restores antiturbulent and hemorrheological properties of blood, increases systemic oxygen transport, and reduces hypoxic acid-base balance disturbances.

[The main pharmacokinetic parameters of p-tyrosol upon intravenous injection in rats. II. Verification of the pharmacokinetics linearity and evaluation of the possible accumulation].

The main pharmacokinetic parameters of p-tyrosol after single (in 3 doses) and repeated intravenous injection were studied in rats. The content ofp-tyrosol in the blood plasma was determined by spectrofluorimetric method. The pharmacokinetic parameters of p-tyrosol are linear in the dose range from 50 to 200 mg/kg. Repeated administration leads to accelerated metabolic elimination of p-tyrosol.

[Hemodynamic and rheological effects of polyetox in rats with crush syndrome]. / Gemodinamicheskie i reologicheskie éffekty poliétoksa u krys s sindromom dlitel'nogo razdavlivaniia.

Polyetox, a medicinal form of high-molecular-weight poly(ethylene oxide) (HMWPEO) improved peripheral blood supply, normalized the overall oxygen consumption, decreased erythrocyte aggregation, and reduced blood viscosity at low shear rate, and restored the antiturbulent properties (hydrodynamic index) of blood in the experiments on rats with crush syndrome. In rats with low resistance, polyetox increased the cardiac output.

[Hemorheological effects of polyethylene oxide in rats with acute myocardial ischemia]. / Gemoreologicheskie éffekty poliétoksa u krys s ostroi ishemiei miokarda.

The effect of polyetox, a medicinal form of high-molecular-weight poly(ethylene oxide) (HMWPEO) on the rheological properties of blood and the necrotic zone size was studied in rats with an acute myocardial ischemia model (on the 5th day after coronary artery occlusion). The drug was infused intravenously in a single daily dose over a period of three days, which resulted in a final HMWPEO concentration of 1 x 10(-6) g/ml in the blood. The first treatment was carried out 1 h after coronary artery occlusion. Animals in the cotrol group with myocardial infarction exhibited high blood viscosity syndrome with stable decrease in the hydrodynamic index. The administration of polyetox reduced blood viscosity, decreased the erythrocyte aggregation, and increased the antiturbulent properties (hydrodynamic index) of the blood. The myocardial infarction zone decreased by 38%, which was manifested in improved EEG parameters.

[Laxative effect of poly(ethylene oxide) 1500 per se and in combination with bisacodyl]. / Slabitel'nyi éffekt poliétilenoksida 1500 per se i pri sovmestnom primenenii s bisakodilom.

The results of experiments on rats showed evidence of a laxative activity of poly(ethylene oxide) (PEO-1500) upon peroral administration. This effect is related to the polymer ability of retaining water, which increases the intestinal content volume and accelerates the intestinal peristaltic activity. The anticonstipative effect of PEO-1500 is comparable to that of forlax, but less pronounced than the effect of bisacodyl. The joint administration of PEO-1500 with bisacodyl produces a synergistic effect exceeding the separate action of both agents.

[Evaluation of major pharmacokinetic parameters of high molecular weight polyethylene oxide using polymer hydrodynamic properties]. / Otsenka osnovnykh farmakokineticheskikh parametrov vysokomolekuliarnogo polietilenoksida s ispol'zovaniem gidrodinamicheskikh svoistv polimera.

The pharmacokinetics of high-molecular-weight polyethylene oxide (HMW PEO)--a parent compound in the polietoks drug--was experimentally studied in cats. A PEO concentration in the blood was determined by measuring a decrease in the hydrodynamic resistance for a blood sample flowing in the turbulent mode via a glass capillary. Variation of the polymer concentration in the blood is described by a single-exponent function with an elimination halftime of T1/2 = 3.15 h. According to the calculation, 99.6% of the initial amount of PEO losses the antiturbulent activity within 24 h.

[The pharmacokinetics of poliosm]. / Farmakokinetika poliosma.

Experiments were conducted on cats to study the pharmacokinetics of polyosm possessing diuretic and antiedemic properties whose primary acting component is polyethyleneoxide 400. Biexponential dependence of the blood drug concentration on the time with T1/2 values of 41 min and 4.8 h was revealed. In the first 5 h after intravenous infusion of the drug 60.8% of the introduced dose of polyethyleneoxide 400 (1 g/kg) was excreted through the kidneys.