Research Results in Pharmacology

Cytotoxicity study of transdermal desloratadine delivery system on murine melanoma and human dermal fibroblast cell cultures

2025-05-15T18:48:25+03:00

treat and prevent allergic conditions, reducing the adverse effects associated with oral administration.

Materials and Methods: We evaluated the cytotoxicity of the transdermal desloratadinedelivery system in micellar and ionic forms on murine melanoma and human dermal fibroblast cell cultures using the MTT assay and resazurin live cell assay.

Results: The results of the MTT assay demonstrated that desloratadine in micellar and ionic forms had a more pronounced cytotoxic effect on murine melanoma cells than on human dermal fibroblasts. The transdermal system had no effect on cell viability. Desloratadine in micellar or ionic form reduced cell viability: the survival rate of murine melanoma cells was below 50%, while when incubated with the transdermal system, the viability of human dermal fibroblasts was above 70%, indicating no toxicity.

Discussion: The polyvinylpyrrolidone-based transdermal system is not cytotoxic, but the active ingredient, desloratadine, features antiproliferative activity, to a greater extent, in relation to tumor cells.

Conclusion: The obtained results demonstrated the cytotoxic effect of micellar and ionic desloratadine on the tumor culture of murine melanoma and the biocompatibility of the transdermal desloratadine delivery system with human dermal fibroblasts.

The The effect of acute swimming stress, corticosterone, dexamethasone, and fludrocortisone on anxiety-like behavior in mice

2025-04-24T12:47:49+03:00

Introduction: Acute swimming stress (ASS) exerts a biphasic effect on anxiety-like behavior (ALB) in mice, inducing an enhancement and a subsequent decrease in ALB 1 h and 24 h after exposure, respectively. Presumably, this effect may be caused by the activation of mineralocorticoid and glucocorticoid receptors, both during the immediate response to acute stress and after its termination at the phase of adaptive changes. Aim of the Research: Comparative study of the effects of acute swimming stress, corticosterone, dexamethasone, and fludrocortisone on ALB in mice 1 h and 24 h after stress exposure or administration of the studied substances.

Materials and Methods: To model ASS in adult male ICR mice, the forced swimming test (FST) was employed. ALB was assessed in mice in the open field test 1 h and 24 h after FST or systemic administration of corticosterone (20 mg/kg), dexamethasone (10 mg/kg), and fludrocortisone (0.04 mg/kg).

Results: Central activity and anxiety index were increased 1 h after exposure to FST, while an increase in the anxiety index was observed 24 h after exposure to FST in the open field test compared to the non-stressed mice. Corticosterone, dexamethasone, and fludrocortisonedecreased central activity and anxiety index 1 h after the administration, compared to the control group. However, fludrocortisone decreased central activity and total locomotor activity 24 h after administration compared to the control group.

Conclusion: A similar pattern of enhancement of anxiety-like behavior was observed in mice 1 h after FST or the administration of corticosterone (single dose 20 mg/kg, i.p.), dexamethasone(single dose 10 mg/kg, i.p.), and fludrocortisone (single dose 0.04 mg/kg, i.p.). Nonetheless, 24 h after exposure to stress or administration of the studied substances, FST decreased ALB, fludrocortisone enhanced ALB, while corticosterone and dexamethasone showed no effect on ALB in mice 24 h after exposure to stress or administration of the studied substances.

Cardiotropic medicinal products of plant origin. Prospects for use in modern clinical practice

2025-03-31T14:11:56+03:00

Introduction: The aim of the research was to study the current state of use and improvement of the prospects for the using cardiological medicinal products obtained on the basis of medicinal plant raw materials.

Materials and Methods: The work used content analysis, monitoring of scientific articles using the databases PubMed, Scopus, Google Scholar, ResearchGate, analysis of the nomenclature of the State Register of Medicines of the Russian Federation (2024) and the Register of Medicines of Russia (2024).

Results and Discussion: The study revealed that diseases of the cardiovascular system are some of the most common causes of death among the population, with at least 37.7 million people suffering from varying degrees of heart failure alone. Despite the constant growth of the range of medicines for the treatment of cardiovascular diseases, medicinal plants and preparations based on them, which are more often used in complex therapy, still play an important role in their therapy. In this review, we consider drugs derived from medicinal plant raw materials used for the treatment of heart failure and arrhythmia of various etiologies, as the most serious cardiovascular pathologies.

Conclusion: Preparations based on herbal remedies with cardiotropic and antiarrhythmic effects are relevant in the treatment of cardiovascular diseases. Cardiotropic action is characteristic of the group of cardiac glycosides, and antiarrhythmic activity is more pronounced in alkaloids and flavonoid substances. Taking into account the prospects for the use of herbal preparations with cardiotropic effects in the complex therapy of cardiovascular diseases, an important and unsolved problem today remains the problem of their interaction with other drugs, which in the future can be solved by creating artificial intelligence programs that contribute to the formation of optimal prescriptions for a particular patient.

Assessment of physiological parameters in the application of a double adeno-associated virus 9 with a codon-optimized DYSF gene for limb girdle muscular dystrophy type R2

2025-03-20T15:33:26+03:00

Introduction: Gene therapy for Myoshi myopathy is extremely relevant, as it may become the first pathogenetic treatment for dysferlinopathy. The aim of this study was to study the efficacy and safety of the use of a genetic construct, the AAV9-DYSF-DV3’ virus, for the treatment of limb girdle muscular dystrophy LGMD) type R2.

Materials and Methods: Mouse models of limb girdle muscular dystrophy type R2 В6.А-Dysf^prmd/GeneJ were used to study the effectiveness of AAV9.DYSF drug and the corresponding C57BL/6J controls were used. During the study, muscle activity was determined on the basis of the following tests: “Grip test”, “Holding an animal on a slippery surface of a vertical rod”, “Forced swimming with a load”, and ”Wire hanging”. In the course of acute and subchronic toxicity, hematological and biochemical blood tests of the rats, histological analysis and ”Open field” behavioral testing were performed.

Results and Discussion: In this study, for the first time, a comprehensive investigation of the effectiveness of gene therapy using the two-vector system of adeno-associated AAV9-DYSF-DV3’ virus with overlapping DYSF cDNA sequences was conducted in a mouse model of limb girdle muscular dystrophy type 2 R.

Conclusion: During the testing of the drug’s effectiveness, it was discovered that drug AAV9.DYSF showed the best effectiveness in mice with the absence of the protein dysferlin in behavioral testing at the maximum dose (5*10¹²) with a double intramuscular injection. In the “Grip test”, the index in В6.А-Dysf^prmd/GeneJ mice increased by 29% (p=0.0026) relative to that in the K-group. In the tests “Forced swimming with a load”, ”Wire hanging”, and ”Holding an animal on a slippery surface of a vertical rod”, the indicators also improved by 80% (p=0.0019), 104.8% (p=0.001) and 20% (p=0.025), respectively, relative to those of the negative control. During acute and subchronic toxicity, the administration of the drug to animals does not cause death or intoxication.

Effect of social isolation and kisspeptin analogues (KS6 and KS10) on the expression of KISS1, KISS2, and their receptors in danio rerio

2025-06-11T13:02:46+03:00

Introduction: The kisspeptin system regulates both reproductive and stress-related neuroendocrine functions. In zebrafish (Danio rerio), social isolation disrupts the expression of kiss1, kiss2, and their receptors (kiss1ra, kiss1rb). This study investigates whether kisspeptin analogues KS6 and KS10 can reverse these effects and compares them with the well-known neuropeptide oxytocin.

Materials and Methods: Adult zebrafish were exposed to 48-hour social isolation and treated with KS6, KS10 (0.1 mg/L), or oxytocin (0.019 IU/L). Total RNA was extracted from whole brains, followed by cDNA synthesis and quantitative PCR targeting kiss1, kiss2, kiss1ra, and kiss1rb. Gene expression was normalized to gapdh. Statistical significance was assessed using one-way ANOVA and Student’s t-test.

Results and Discussion: Social isolation downregulated kiss1, kiss2, and kiss1ra, and upregulated kiss1rb. KS6 significantly increased kiss1 expression and normalized kiss1rb levels. KS10 partially restored kiss1 and kiss2, but reduced kiss1ra and further elevated kiss1rb. Oxytocin reversed all isolation-induced changes. KS6 showed the most consistent restorative effects, whereas KS10 demonstrated a more selective receptor profile, suggesting differential downstream signaling.

Conclusion: KS6 effectively reversed social isolation-induced dysregulation of kisspeptin signaling in zebrafish, indicating its potential for modulating neuroendocrine responses to stress. KS10 exhibited selective receptor modulation, which may be valuable for fine-tuned therapeutic strategies. These findings highlight the distinct pharmacological profiles of kisspeptin analogues in stress-related contexts.

Effect of cyclophosphamide on regulation of heart contractions by means of sodium calcium exchanger

2025-02-25T15:37:45+03:00

Introduction: Every year brings in new medications capable to slow or stop proliferation of tumour cells. Unfortunately, in spite of antitumour benefits, new medicines have some side effects that reduce their therapeutic properties.

Materials and Methods: The study was conducted in three series of experiments on 24 whiteWistar rats, both male and female, each weighing 200-250 g. Decapitation of the animal was performed under ether anesthesia with rapid extraction of the heart and perfusion using the Langendorff method. To study NCX in the heart, a perfusion device was used to create a permanent coronary flow. Monitoring the physiological state of the heart when changing the composition of solutions was carried out using a balloon inserted into the left ventricle.Contractions and relaxation of the heart were recorded using an electronic pressure sensor. The parameters were documented and processed using the Zet Lab external module software.

Results and Discussion: In the first series of experiments, the effect of hyposodic solution onthe tone of the left ventricle of the heart stopped by a hyperpotassic medium was studied. The developed technique served as the basis for studying the effect of cyclophosphamide on NCX,accompanied by contraction and relaxation of the heart. Experiments have shown the ability of cyclophosphamide to significantly reduce the rate of the tone increase and the development of contraction force, as well as prolong the relaxation time during NCX.

Conclusion: Cyclophosphamide is able to disrupt the capture of ionized calcium in the cytosolby intracellular Ca-accumulating structures during relaxation of the heart. Unlike controlrecordings, in the presence of cyclophosphamide, repeated relaxations do not occur completely.As a result, each subsequent contraction begins at a higher initial diastole level.

The effect of synthesized 5-R-1H-benzo[d]imidazole-2-thiol derivatives on intraocular pressure in normal and pathological conditions

2025-02-04T15:09:56+03:00

and do not have a resorptive effect is a topical task for the treatment of glaucoma. Eighteen derivatives of 5-R-1H-benzo[d]imidazole-2-thiols were synthesized and studied for ophthalmic hypotensive activity in animals with normal intraocular pressure and in animals with dexamethasone-induced ophthalmic hypertension.

Materials and Methods: Ophthalmohypotensive activity was studied by tonometry with the TonoVet veterinary tonometer in 90 intact and experimental sexually mature mongrel rats weighing 250-350g before and after instillation of solutions of the studied compounds. Local irritant effects were determined by performing a conjunctival test using 25 guinea pigs.

Results: The most active compound among the 5-R-1H-benzo[d]imidazole-2-thiol derivatives was compound 1a, which reduced the ophthalmotonus in normotensive animals by 31.37%, exceeding the effect of the reference drugs timolol (-26.84%) and melatonin (-30.95%), and in rats with dexamethasone-induced glaucoma – by 23.74%, similar to melatonin (-23.72%), but inferior to timolol (-29.75%). It was found that substance 1a has no local irritant effect. It was revealed that at the screening concentration (4 mg/mL), compound 1a has a systemic effect, at lower concentrations, the ophthalmohypotensive effect decreases, the latent period increases, and the severity of the resorptive effect decreases.

Conclusion: The most active compound, 1a, was found to have demonstrated in vivo IOP-lowering activity when administered as a single instillation at a concentration of 0.4% (4 mg/mL) in ophthalmonormotensive animals and animals with steroid-induced glaucoma. Compound 1a was shown to have no local irritant effect.

Predictive analysis and prediction of the main molecular targets for the N-acetyl-6-aminohexanoate derivative

2024-12-31T07:12:28+03:00

Introduction: N-acetyl-6-aminohexanoate (acexamic acid) and its derivatives are actively studied as promising compounds for the creation of new drugs, but their pharmacokinetic parameters and detailed mechanisms underlying a wide range of biochemical activities are still unclear.

Materials and Methods: PASS Online, Molinspiration Property Calculation Service and OSIRIS Property Explorer were used for predictive analysis. To determine the molecular biomarkers of the N-acetyl-6-aminohexanoate derivative – 2-ethyl-6-methyl-3-hydroxypyridinium N-acetylhexanoic acid, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were predicted. Molecular docking was performed using GalaxyWEB Sagittarius service followed by evaluation of the results using RCSB Protein Data Bank and UniProt Consortium databases.

Results: The study of the pharmacokinetic properties of 2-ethyl-6-methyl-3-hydroxypyridine N-acetyl-6-aminohexanoate revealed its potential suitability as a promising drug with high bioavailability. The highest degree of affinity is predicted with the eNOS center – binding energy from -7.2 to -8.3 kcal/mol; the VEGF center – binding energies from -6.1 to -7.7 kcal /mol, and the RANKL centre – binding energies from - 6.0 - 6,9 kcal mol.

Conclusion: The results of predictor analysis and molecular docking suggest that the N-acetyl-6-aminohexanoate-2-ethyl-6-methyl-3-hydroxypyridinium derivative is a safe and promising compound. Potential biotargets include eNOS, VEGF, and RANKL.

Pharmacotherapy of arterial hypertension: assessment of knowledge levels among students and practicing physicians. Results of the PHYSTARH-II Project

2024-12-31T07:11:55+03:00

Introduction: Arterial hypertension (AH) is a significant risk factor for cardiovascular diseases and premature mortality. The aim of the study: To assess the level of knowledge and cognizance of physicians and medical students in a field of pharmacotherapy of AH.

Materials and Methods: This article analyzes the second phase (2019-2023) of the PHYSTARH project, a multicenter anonymous survey involving 494 therapeutic physicians from 10 Russian cities/regions and 426 students from 10 Russian and Kyrgyz universities. Comparisons were made with the previous phase (2017-2019) of student and physician research. Statistical methods included descriptive statistics, Kolmogorov-Smirnov, U-Mann-Whitney, Kruskal-Wallis, Pearson correlation, median test, ANOVA, and regression analysis (p<0.05).

Results: The study revealed that the knowledge levels among both students and physicians is not sufficiently high. Moreover, some questions showed a fatally low level of knowledge. The average level of correct answers in the second part of the survey (LCA) was 44.9% for students and 53.5% for physicians. The LCA for students in the previous phase was 57.7%, while the LCA for physicians (2017-2019) in the second part of the survey was 60%.

Conclusion: The common level of knowledge base among students and physicians regarding key aspects of AH is insufficient. It is essential to implement additional educational programs to fill the recognized knowledge gaps. The results of studies highlight the necessity of improving educational programs for medical specialists in the field of arterial hypertension. The lowest correct answers rates were found in questions regarding the use of acetylsalicylic acid in patients with AH. The highest correct response rate was recorded for a question about selecting the optimal drug for managing uncomplicated hypertensive crises.

Experimental evaluation of osteogenic activity of certain hormonal drugs

2024-12-30T17:30:59+03:00

Introduction: The necessity of extra medicamental stimulation of bone tissue regeneration in addition to basic surgical method of treating fractures is usually determined by osteoporosis or high severity of injury. One of the lesser-studied options for osteogenic hormone therapy of fractures is the use of human chorionic gonadotropin(hCG). The aim of the study: Conducting an experimental evaluation of the osteogenic activity of hCG in its systemic and local application based on a model of perforated fracture of femoral bone in laboratory white rats.

Materials and Methods: The experimental perforated femoral fracture in 64 male Wistar laboratory rats was modeled by drilling a circular bone defect with a 1.4 mm diameter. The osteogenic effect of the studied hormonal drugs (hCG and thyrocalcitonin) compared with a reference agent from the bisphosphonate group – zoledronic acid, after a course of injectable treatment was assessed according to the rate of bone defect recovery using digital radiography. In addition, the same method was used to experimentally evaluate the local osteogenic activity of hCGand zoledronate introduced into the bone marrow canal of the damaged bone via a patented original intramedullary metal construction for osteosynthesis.

Results and Discussion: Upon administering the studied hormonal drugs by injection, significant osteogenic activity was observed, with a more pronounced effect for hCG, although still inferior to that of the reference pharmacotherapy. The intra-bone local application of hCG showed results practically equal to the osteogenic effect of zoledronate.

Conclusion: As a result of the experiment, a high therapeutic effect of hCG on bone tissue regeneration was discovered, which, with local application (intramedullary implants soaked in hCG solution with a concentration of 5000 IU/mL), reached the level of zoledronate’s effect (intramedullary implants soaked in solution with a concentration of 0.8 mg/mL), but without the toxic side effects typically associated with the reference pharmacotherapy.