[Investigation of ligand-receptor interaction and biodistribution of a drug containing cattle retinal polypeptides in various administration routes]. / Issledovanie ligand-retseptornogo vzaimodeistviya i bioraspredeleniya pri razlichnykh rezhimakh vvedeniya lekarstvennogo sredstva, soderzhashchego polipeptidy setchatki glaz skota.

It is important to understand the features of the interaction of drug components with body receptors and obtain data on its distribution in various administration routes in recommended doses in order for its usage in clinical practice to be safe and effective. PURPOSE: To investigate in vitro the interactions of a drug consisting of water-soluble polypeptide fractions produced on animal retina with a wide range of receptor targets, and to assess its biodistribution in the organs of laboratory animals. MATERIAL AND METHODS: The biodistribution of the radioactively marked drug in different organs and tissues of laboratory mice in various routes of administration was studied at the National Research Centre «Kurchatov Institute¼. Evaluation of the ligand-receptor interaction of the drug was carried out in the laboratory at Eurofins Pharma Discovery Services by the method of competitive radioligand binding. RESULTS: A significant effect of the interaction of the polypeptide drug was revealed with different subtypes of glutamate receptors: AMPA, NMDA, and mGluR1. As a result of an in vivo test, we have obtained biodistribution data of the drug for intravenous, intramuscular and parabulbar administration, and the dynamics of drug accumulation in the tissues of the brain and eyes. CONCLUSION: According to the study results, the peptide drug binds to receptors associated with the loss of retinal ganglion cells. Interaction with these receptors potentially provides the test subject with neuroprotective effect. The content dynamics of the studied drug in the blood of animals depends on the route of administration and the amount of drug administered. At the time point of 0.5 hours for intravenous and intramuscular administration in the dose of 1.7 mg/kg, the studied drug has sufficiently high bioavailability in the tissues of the brain and eye. The data suggest that the main route of excretion of the studied drug is through kidneys.

[Antioxidant effect of cortexin, cerebrolysin and actovegin in rats with chronic cerebrovascular insufficiency]. / Antioksidantnoe deistvie Korteksina, Tserebrolizina i Aktovegina u zhivotnykh s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To compare the antioxidant effects of cortexin, cerebrolysin and actovegin in rats with chronic brain ischemia. MATERIAL AND METHODS: Chronic brain ischemia was modeled in male rats by 50% stenosis of the common carotid arteries. Forty days after surgery, the animals received 2 ten-day courses of therapy, separated by a break of 10 days. Placebo, cortexin (0.3, 1 and 3 mg/kg), cerebrolysin (0.8, 2.5 and 7.5 ml/kg) and actovegin (5 ml/kg) were administered to animals as treatment. The concentration of malondialdehyde (MDA) in the homogenates was determined by the reaction with thiobarbituric acid, the concentration of reduced glutathione was determined by the reduction reaction of 5.5-dithiobis- (2-nitrobenzoic acid); determination of catalase activity, as well as the content of lactate and pyruvate, by commercially available reagent kits. The activity of superoxide dismutase (SOD) was determined by the photometric method based on an assessment of the degree of inhibition of the epinephrine oxidation reaction. All reactions were carried out in triplicates. RESULTS: Modeling of chronic brain ischemia led to the statistically significant decrease in the content of lactate and pyruvate (p<0.001, when compared with the control group), which was not accompanied by a significant decrease in their ratio (p>0.05), as well as to the decrease in SOD, catalase activity, restored glutathione and increase in MDA concentrations. Compared with the control group, in the groups that received cortexin at a dose of 3 mg/kg/day, cerebrolysin at a dose of 7.5 ml/kg/day and actovegin at a dose of 5 ml/kg/day, there were an increase in the content of lactate and pyruvate (without a significant change in their ratio), restoration of glutathione levels and the activity of SOD and, to a lesser extent, catalase, combined with a decrease in the concentration of MDA. CONCLUSION: Course administration of cortexin (3 mg/kg), cerebrolysin (7.5 ml/kg) and, to a lesser extent, actovegin (5 ml/kg) has a positive effect on the state of the antioxidant system of the brain in rats with chronic brain ischemia.

[Electroretinography in evaluation of neuroprotective effect in an experimental model of glaucoma]. / Elektroretinografiya v otsenke neiroprotektornogo effekta na modeli eksperimental'noi glaukomy.

For drugs that have a therapeutic effect on glaucoma through mechanisms not associated with decreasing intraocular pressure (IOP), special attention is paid to the choice of effectiveness criteria. The article examines the possibility of using a- and waves of electroretinography (ERG) in preclinical studies to predict the effectiveness of glaucoma drug candidates. PURPOSE: To examine the possibility of reliably associating changes in the amplitude of a- and ERG waves with functional changes in the retina of experimental glaucoma rats with morphological evidence of loss of functional integrity of the retina. MATERIAL AND METHODS: The study was carried out in the laboratory of the Research Institute of Pharmacology of Living Systems of the Belgorod State University. Adult outbred rats were used as a test system. Experimental glaucoma was modelled by multiple injections of hyaluronic acid into the anterior chamber of the eye; they were examined by recording the time history of intraocular pressure changes, and performing ERG, ophthalmoscopy, and histological examination of the retina and subcortical centers of vision. The following groups were formed: intact, pathology control, positive control. RESULTS: The development of glaucoma in experimental rats was accompanied by neuronal death in the ganglionic layer of the retina; at the same time, characteristic changes were observed in the subcortical visual centers. A change in the ERG was recorded: for thewave, there was a dependence on the degree of changes in the ganglionic layer of the retina, change in the wave can also indicate the involvement of amacrine and horizontal cells in the process; for the a-wave, a correlation with the results of photoreceptor layer histology was noted, which was characterized as a deviation from the norm developing against the background of hydrodynamic load in the eye chambers. CONCLUSION: ERG is suitable for use in preclinical studies of glaucoma drugs as an indicative in vivo method for diagnosing the state of the retina in animals. The use of this method is especially valuable for conducting preclinical studies of drugs that involve long-term use when ophthalmoscopy and intraocular pressure alone cannot fully characterize the course of glaucoma, and animal euthanasia seems unnecessary and inhumane.

[Comparative study of protective effects of Cortexin, Cerebrolysin and Actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia]. / Sravnitel'noe izuchenie vliyaniya Korteksina, Tserebrolizina i Aktovegina na sostoyanie pamyati, mozgovoe krovoobrashchenie i strukturu gippokampa u krys s khronicheskim narusheniem mozgovogo krovoobrashcheniya.

OBJECTIVE: To compare the effects of cortexin, cerebrolysin and actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia. MATERIAL AND METHODS: The study was conducted using male rats with chronic brain ischemia caused by stenosis of the common carotid arteries by 50%. Animals received cortexin (0,3; 1 or 3 mg/kg), cerebrolysin (0,8; 2,5 or 7,5 ml/kg) and actovegin (5 ml/kg) in two 10-day courses with 10 days of treatment break. The severity of cognitive impairment was evaluated using the Morris water maze, passive and active avoidance tests. Cerebral circulation using laser flowmetry and brain hippocampus structures were studied in the end of treatment. RESULTS: Cognitive impairment in animals with chronic brain ischemia was accompanied by the development of pathological changes in the CA1 and CA4 regions of the hippocampus. Administration of cortexin (1 and 3 mg/kg) and cerebrolysin (2.5 and 7.5 ml/kg) to rats with chronic brain ischemia had almost no effect on cerebral blood flow, but contributed to the improvement in memory formation and retrieval processes in the Morris water maze. The treatment effect was comparable for both drugs and persisted after 10 days of treatment break. Morphological assessment showed a decrease in the severity of pathological changes in the hippocampal regions. CONCLUSION: The course-administration of cortexin and cerebrolysin lead to a decrease in the severity of memory impairment and pathomorphological changes in the hippocampus in rats with chronic brain ischemia.

[Evaluation of the cardioprotective effect of ubiquinol on the model of reperfusion injury of rat myocardium]. / Otsenka kardioprotektornogo deistviia ubikhinola na modeli reperfuzionnogo povrezhdeniia miokarda krys.

The cardioprotective effect of ubiquinol on the model of myocardium reperfusion injury in rats was investigated. The study was carried out using mature males of outbred rats. Myocardial ischemia-reperfusion injury was performed after 30-minute ligation of the left coronary artery followed by reperfusion. The main criteria for assessing the development of pathology included the results of electrocardiography, biochemical analysis of blood plasma, histological and histochemical study of the myocardium. Development of the reperfusion damage of the myocardium caused specific changes in non-treated animals. The best therapeutic effect on biochemical indices was provided by a drug with the known cardioprotective activity - Mexidolâ and the tested object ubiquinol at doses of 2-6 mg/kg. Evaluation of the results of electrocardiography allowed to confirm the development of ischemic myocardial damage in all groups. The results of histochemical and histological examination of the myocardium suggest a high cardioprotective activity of ubiquinol at a dose of 3 mg/kg and a potential cardioprotective effect of ubiquinol in doses closest to the therapeutic doses of 2 and 6 mg/kg. Ubiquinol is a dose 9 mg/kg showed signs of prooxidant activity, manifested in the form of aggravation of reperfusion injury of the myocardium. The most effective in the conditions of experimental pathology is 1% solution of ubiquinol, at a dose of 3 mg/kg, whose cardioprotective effect is comparable or higher than that for the reference drug Mexidolâ at the therapeutic dose. In doses that are greater than therapeutic ubiquinol is able to act as a pro-oxidant.