Genetic differences in different populations influence the mechanism and efficacy of drugs. Biomodels that take into account the peculiarities of genetic polymorphism in different individuals allow to more fully investigate the molecular-genetic mechanisms of action of pharmacological agents, including immunobiological ones. Recombinant DNA encoding a hybrid MHC class I protein containing human ß2-microglobulin fused with antigen-presenting domains (α1 and α2 domains) of the HLA-C*07:02:01:01 molecule and α3 domain of the mouse H2-complex was created. The purified linearized DNA fragment containing the target construct flanked by regulatory fragments ensuring its stable transcription was used to obtain a new line of humanized transgenic mice. The principles of designing humanized transgenic mice by encoding a chimeric MHC class I protein containing antigen-presenting domains HLA-C*07:02:01:01 are similar to those for obtaining mice of the HLA-А*02:01:01 and HLA-B*18:01:01:02 humanized transgenic lines. These transgenic lines of laboratory mice are independent biomodels, and also be used as baselines for obtaining corresponding transgenic and knockout lines.

This paper presents a study into the pharmacokinetics of a new inhaled anti-inflammatory hexapeptide, registered as “Leutragin”. This drug is used as a new treatment approach for viral pneumonias, whose severe course is directly related to the cytokine inflammatory cascade referred to as a cytokine storm. The study involved investigation of lung tissue and serum after a single inhalation administration of Leutragin to mice of the C57BL/6Y line at a dose of 150 mg/kg. The time required to reach the maximum concentration (Tmax) of Leutragin in serum and lung was 30 min and 10 min, respectively. The maximum concentration (Cmax) in lung was 358.5 ng/g, which exceeded the concentration maximum for blood (53.84 ng/g) by over six times. It was found that, after inhalation administration, Leutragin is rather rapidly eliminated from the body with the half-life of the drug (t1/2el) from blood serum and lungs ranging from 25.8 to 38.9 min.

This study examined the effect of peptide extracts from the epiphysis-pituitary gland of Reindeer (Rangifer tarandus) and a delta sleep-inducing peptide, simulating a modified release of drugs, on the spontaneous motor activity of male rats under the conditions of light desynchronosis. The study revealed changes in spontaneous motor activity under the influence of extracts of a peptide nature and a delta sleep-inducing peptide under the following polar light regimes. Under the conditions of constant lighting and constant darkness, an increase and a decrease in activity was observed, respectively. Under normal lighting, peptide extracts showed increased efficacy. This method of pharmacological adjustment of the body’s circadian oscillators using modified-release peptides can be used to develop a scheme for correcting light desynchronosis.

This work presents the results of primary pharmacological screening of anticholinergic drugs and comparative evaluation of their specific activity in equitoxic concentrations using Daphnia magna Straus hydrobionts as a biological test object. We determine the protective index and the minimum effective concentration in terms of preventing atypical motor hyperactivity of pharmacological substances when poisoning with a reversible acetylcholinesterase inhibitor. On the basis of the results obtained, the list of promising candidates for further research in warm-blooded animals is extended by all of the anticholinergic drugs previously selected in experiments on mammals.

The article presents the results of a study into the effect of carnosine on oxidative damage to the kidneys in experimental diabetes mellitus. The experiment was carried out using two groups of Wistar rats: control (n=8) and experimental (n=11). In both groups, streptozotocin-induced diabetes mellitus was simulated for eight weeks. Experimental animals were intragastrically injected with carnosine (15 mg/kg) from weeks 4 to 8. The concentration of glucose, protein and creatinine excretion in urine were determined. At the end of eight weeks, the kidneys were removed from the rats to determine the indicators of oxidative stress severity (concentration of thiobarbiturate-reactive products, total antioxidant activity, activity of catalase, superoxide dismutase, glutathione peroxidase) and to conduct morphometry of the size of the renal glomeruli, the area of the vascular bed, capillaries and mesangium in the glomeruli, the number of podocytes. A comparison with the control showed the use of carnosine led to a 1.5-fold decrease in the concentration of thiobarbiturate-reactive products (p<0.001), a 2.2-fold increase in the total antioxidant activity (p<0.001), and a 1.2-fold increase in catalase activity (p=0.039). The area of the renal glomeruli and the mesangium in this group decreased by 1.6 times (p<0.001 and p=0.04, respectively). The total area of blood flow increased by 2.4 times (p<0.001), the area of one capillary, and the number of podocytes in the glomerulus increased by 1.9 times (p<0.001 and p=0.001). A 3.5-fold decrease in protein concentration in urine was also noted (p=0.007). Therefore, inhibition of the formation of advanced glycation end products by carnosine in experimental diabetes mellitus attenuates oxidative damage to the kidneys. This is evidenced by a decrease in proteinuria, an increase in the number of podocytes, a decrease in the area of the renal glomeruli, and an improvement in the condition of the glomerular vascular system.

We investigate effects of glyproline-type neuropeptides on lipid and protein peroxidation in the hypothalamic brain region of rats under the conditions of experimental hyperthyroidism. The state of hyperthyroidism in animals was simulated by intragastric administration of sodium pentahydrate of L-thyroxine at a dose of 150 µg/kg for 21 days. The following experimental groups (n=10) were formed: 1) control group — intact animals (control); 2) animals treated with L-thyroxine sodium salt pentahydrate (hyperthyroidism); 3) animals treated with Thr-Lys-Pro-Arg-Pro-Gly-Pro (celank); 4) animals treated with Pro-GlyPro (doses of 87 and 33 µg/kg/day, respectively) intraperitoneally daily during 21 days starting one day after the last administration of sodium pentahydrate of L-thyroxine. The level of lipid peroxidation processes was assessed by the initial level of TBA-reactive products, spontaneous and ascorbate-dependent lipid peroxidation rates in hypothalamic tissue homogenate. Protein peroxidation products were determined by the reaction between oxidized amino acid residues of proteins and 2,4-dinitrophenylhydrazone. The enzymatic part of the antioxidant system of hypothalamic region was estimated by measuring the activity of superoxide dismutase and catalase. In the setting of Thr-Lys-Pro-Arg-Pro-Gly-Pro and Pro-Gly-Pro administration under experimental hyperthyroidism, the intensity of lipid and protein peroxidation processes was decreased, while the activity of antioxidant enzymes-superoxide dismutase and catalase was restored in the hypothalamic tissue. The experimental data obtained indicate that, under the conditions of experimental hyperthyroidism, Thr-Lys-Pro-Arg-Pro-Gly-Pro and Pro-Gly-Pro compounds exhibit an antioxidant and antiradical activity with respect to parameters of lipoperoxidation and oxidative modification of proteins, as well as with respect to enzymatic defense systems in the hypothalamic brain region of laboratory animals.