Vol 20, No 3 (2022)

The hunger hormone, ghrelin, is produced not only in response to food deprivation, but is also released during various types of stress. In recent years, the rise in ghrelin levels has come to be seen as an essential component of the stress response. The review is devoted to ghrelin-dependent mechanisms providing reciprocal interaction between the hypothalamus–pituitary–adrenal cortex axis and the dopaminergic reward system. Direct and feedback links between the stress-realizing system of the paraventricular nucleus, the neural networks of the lateral hypothalamus and the arcuate nucleus (which form the centers of hunger/satiation), and the mesolimbic reward system are considered. The role of peripheral satiety hormones and glucocorticoids in the regulation of motivation and reinforcement is discussed, as well as the involvement of endogenous opioid and endocannabinoid receptors in the “learning” of dopaminergic neurons in the ventral tegmental area and the hippocampus.

Diabetes mellitus is a predictor of the severe course of a new coronavirus infection and high mortality, in this regard, the selection of appropriate hypoglycemic therapy is a vital issue. In this article, we paid attention to dipeptidyl peptidase-4 (DPP-4) inhibitors, since this group of drugs has features like low risk of hyperglycemia and immuno-mediated effects. For the most effective treatment, it is necessary to take into account the individual characteristics of each patient, namely, the achievements of pharmacogenetics. The genetic variability of the response to therapy with DPP-4 inhibitors is due to a variety of polymorphisms, several main variations are considered in the review. The ambiguity of the available studies on the effectiveness of DPP-4 inhibitors in patients with type 2 diabetes with COVID-19 indicates the need to continue pharmacogenetic studies. The combination of knowledge about the subtleties of the mechanisms of pharmacological action of drugs and individual characteristics of pharmacodinamics will ensure the greatest effectiveness and safety of personalized therapy of diabetes mellitus against the background of coronavirus infection.

BACKGROUND: The development of effective drug delivery to the central nervous system still remains an important problem in pharmacology despite the rapid development of a large number of new treatment strategies in recent years. Recently interest of the intranasal method as delivery route has greatly increased because this method of administration allows to bypass the blood-brain barrier. There is not a single fundamental study comparing intranasal, central and peripheral methods of administration in order to determine the feasibility of using the intranasal route for delivering substances to the brain by far.

AIM: Aim is to study the effect of 6-hydroxydopamine (6-OHDA), a neurotoxin that does not penetrate through the blood-brain barrier by various administrations on the behavior of mice.

MATERIALS AND METHODS: The experiments were performed on 40 outbred female mice weighing 20–25 g. The mice were divided into groups of 10 which were injected with intraventricular, intranasal, intraperitoneal, and intact 6-OHDA. After 21 days, behavioral responses were observed in the Rotarod test, Verticalization, Open Field, and Pole test.

RESULTS: 1. A significant difference was found between animals after intraventricular administration of 6-OHDA and the intact control group when studying the behavior of animals in the “open field” test. 2. The study of coordination activity in the Rotarod test (rotating rod) showed a similar decrease in the retention time on a rotating drum in animals after intranasal and intraventricular administration of 6-OHDA. 3. Only the descent time increased after intranasal administration of 6-OHDA. 4. A significant increase in the motor activity of mice was revealed after intranasal and intraventricular administration of apomorphine in the verticalization test.

CONCLUSIONS: It was concluded that a neurotoxin that does not pass through the blood-brain barrier into the central nervous system penetrates through after intranasal administration.

BACKGROUND: Phenosanic acid is a synthetic antioxidant, the active ingredient of the original domestic drug recommended for the treatment of epilepsy. To improve the effectiveness and safety of the use of phenosanoic acid, additional study of its pharmacokinetic properties is necessary.

AIM: To study the pharmacokinetic parameters of the active ingredient of the drug Dibufelon, capsule 200 mg (LLC “Piq-Pharma”, Russia) in vitro and in vivo systems in rats after single administration in one dose.

MATERIALS AND METHODS: Phenosanic acid binding to blood plasma proteins, microsomal stability and permeability through the monolayer of Caco-2 cells were evaluated in in vitro tests. The pharmacokinetics parameters were studied after a single intragastric administration in Wistar rats in dose of 80 mg/kg. The samples were analyzed by HPLC-UV.

RESULTS: A high variability in the degree of binding of phenosanic acid to blood plasma proteins by 20–65% depending on the concentration was revealed, relatively high microsomal stability (half-life — 1106 ± 789 min, internal clearance — 2.05 ± 0.86 μl/min/mg protein of liver microsome; residual content after 60 min incubation — 87.9 ± 7.8%) and the ability to penetrate through the monolayer of cells Caco-2. The rapid absorbtion of the substance into the systemic bloodstream was established — its maximum concentration in blood plasma was observed already 3.6 ± 1.2 hours after administration, and its slow removal from the systemic bloodstream — the half-life was about 19 h, the average retention time was about 29 h. Phenosanic acid with different degrees of intensity was distributed to all the examined organs and tissues: kidneys > liver > brain > omentum > muscle, and invariably excreted in a small amount with urine and feces, about 0.04% and 5.5%, respectively.

CONCLUSIONS: As a result of the study, it was found that phenosanic acid is characterized by rapid absorbtion into the systemic bloodstream and a long stay in it invariably, which may be due to the peculiarities of its binding to blood plasma proteins and relatively high metabolic stability, revealed during the corresponding in vitro tests. The study of the permeability and transport of phenosanic acid showed that it can presumably be attributed to compounds with medium permeability and is not a substrate for the transport protein P-glycoprotein (P-gp). The study of tissue availability of phenosanic acid confirmed its entry into peripheral tissues, including the brain, which is the area of implementation of the anticonvulsant effect.

BACKGROUND: The search of effective and safe drugs to prevent and treating the immune deficient states is an actual problem of modern medicine.

AIM: The purpose of the study is to evaluate the effect of Serratula marginata dry extract on structure of mice thymus and spleen at cyclophosphamide immunosuppression.

MATERIALS AND METHODS: The experiments were carried out on F1 (CBAxC57Bl/6) mice. Immune deficiency was simulated by a single intraperitoneal introduction of cyclophosphamide in the dose 250 mg/kg. S. marginata dry extract in the dose 100 mg/kg was administered to animals for 14 days intragastrically against cyclophosphamide. Morphological studies of the thymus and spleen were performed on day 16 after the extracts administration. Areas white and red pulp of the spleen; the area of the thymic lobule, the cortex and the medulla; the density of cells in the subcapsular zone and the deep layers of the cortex were measured using the Zen 2012 image analysis program.

RESULTS: The S. marginata extract limited the development of involutive changes in the thymus caused by cyclophosphamide: the thymus area was by 28% (p ≤ 0.05) higher and the cortical-medullary index was (ratio of the cortex area to the medulla area) by 26% higher. The number of mitotically dividing cells, blasts and large lymphocytes increased, the number of cells with structural disorders and macrophages decreased in the thymus cortex. In animals of the experimental groups, the white pulp area was 47% (p ≤ 0.05) higher than that in the control.

CONCLUSIONS: The S. marginata dry extract limited the development of involutive processes in the thymus and spleen caused by the introduction of cytostatic cyclophosphamide.