Os In Dose Research Articles

THE IMPACT OF CHOLECALCIFEROL ON THE REPRODUCTIVE SYSTEM FUNCTION IN RATS MALES WITH EXPERIMENTAL GONADOPATHY

Actuality. Nowadays, the disturbances of men’s reproductive function are the important problem which often accompany sex glands diseases. During last years, scientific researchers are taking into consideration vitamin D with aim to create safe medicines or treatment schemes for therapy hypofertility developed due to gonadopathies. It is thought, Vitamin D may improve not only spermogramm, but, probably, acts on men’s reproductive ability by influencing fertility. The correction of reproductive disturbances requires the experimental grounding of vitamin D and its complex schemes using on the infertility experimental models. The aim of this investigation was to determine the condition of rat males’ reproductive system with experimental damage of testicles during correction by vitamin D3. Materials and methods. The correction by vitamin D3 (cholecalciferol) as a monotherapy or together with Tribestan® has been carried out in Vistar rats with experimental gonadopathy induced by Serotonin hydrochloride. The drug of comparison Tribestan® has been introduced per os in dose of 68 mg/kg body mass three days before Serotonin hydrochloride introduction; under the condition of serotonin obtaining (14 days) and during three days after its last injection once a day. Vitamin D3 has been given according to the same scheme in value of 0,5 ml in dose of 4000 IU (per os). The male fertility has been determined according to fertility and fecundity indices of rats’ females fertilized by experimental rats’ males. Due to results of mating with intact females the integral index of average realized fecundity (fertility) of rats’ males has been calculated. The researches of spermatogenesis has been carried out in epididymis’s suspension, the morphometric indices were studied on the histological sections. Results. Under the condition of serotonin induced gonadopathy the disturbance of all indices of fertility and reproductive function has been observed. The introduction of cholecalciferol as a monotherapy during three weeks has statistically increased the part of motile epididymal sperms relative to gonadopathy, but not reaching the intact animals level; the number of spermatogonia and index of spermatogenesis have been normalized. However, the vitamin D using hasn’t influenced general number and percentage of pathological forms of sperm cells in rats with modelled testicles damage; hasn’t improve males’ fertility. The introduction of vitamin D3 together with Tribestan to rats mails with serotonin induced testicles damage has positively affected all the spermogramm and gonads morphometric indices. The fecundity, as an embryonic losses level, has almost declined to Control rats’ values, whereas, the number of alive fetuses in thus group has been statistically higher than in groups with pathology as well as in those animals which obtained only cholecalciferol or referent medicine separately. The index of realized fecundity Fi has normalized in rats obtained vitamin D3 together with Tribestan. Fi in this group was higher than in other experimental animals. Conclusions. The using of cholecalciferol in complex schemes of treating of reproductive system disturbances due to gonads damage has led to improving of reproductive function and may be considered being pathogenetic therapy due to influence the different chains of reproductive health.

Stimulation of the endogenous hydrogen sulfide synthesis restores constitutive nitric oxide synthesis and endothelium-dependent vasodilation in old rats

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hydrogen sulfide (H2S) is a gas transmitter of endogenous origin, which has an important regulatory function in the human body. Endogenous H2S is synthesized by three enzymes, cistationine-β-synthase (CBS), cistationine-γ-liase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MTS), which is coupled to the activity of cysteine aminotransferase (CAT). CAT, CBS, and CSE are pyridoxal-5- phosphate (PLP)-dependent enzymes. It is known that with age the exchange of hydrogen sulfide is disturbed against the background of increasing oxidative and nitrosative stress. At the same time there is a decrease of constitutive synthesis of nitric oxide (NO). Recent studies show that hydrogen sulfide closely interacts with the NO system. Activation of H2S biosynthesis and restoration of its pools in tissues of old animals may be a promising direction of cardiovascular disease prevention. The aim of the current work was to study the effect of H2S-synthesizing enzymes cofactor pyridoxal-5-phosphate (PLP) on the endothelium-dependent relaxation of smooth muscle vessels in old rats, as well as the H2S content and cNOS activity in aortic tissues. Methods Old rats (22-24 months old) were PLP administered per os in dose of 0,7 mg per kg daily for 2 weeks.The content of hydrogen sulfide, activity of cNOS and iNOS was measured in aortic tissues.Vascular reactions were determined in experiments on isolated aortic strips. To clarify the role of either NO or H2S in the endothelium-dependent vasorelaxation, N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (Sigma, USA, 27 mg/kg) or O-carboxymethylhydroxylamine (O-CMH) (50 mg/kg) (Sigma, USA) was injected intraperitoneally 30 min before sacrificing. Results We showed that the H2S content was 1.6 times lower in old rat aorta compared to adult ones. PLP administration for 2 weeks induced a significant increase of H2S content in aortic tissue of old rats (P<0.05). It was found that with aging, the activity of cNOS decreases by 3 times, and the stimulation of endogenous Н2S leads to an increase in the activity of this enzyme in the aortic tissues by 2.1 times as compared with those in old animals. At the same time, the activity of the iNOS enzyme with aging increases by 3.8 times, and after the introduction of PLP, it decreases almost halved. Also shown, that PLP significantly improved endothelium-dependent aortic smooth muscle relaxation in old rats. The amplitude of acetylcholine-induced relaxation which was significantly reduced in old rats was increased more than 2.5-fold. This effect was reversed by inhibitors of NO-synthase and 3-mercaptopyruvate sulfurtransferase indicating the involvement of NO and H2S in the improved endothelium-dependent vascular relaxation. Conclusions Thus, H2S acts as a regulator of the NO system that increases cNOS activity and NO synthesis in aortic tissue, which improves endothelium-dependent relaxation of aortic smooth muscle in aged rats.

Effect of Tilorone on the Dynamics of Viral Load and the Levels of Interferons and Interleukin-1β in the Lung Tissue and Blood Serum of Mice with Experimental Influenza.

We studied the effect of tilorone on the dynamics of IFNα, IFNγ, and IL-1β levels in the lung tissue and blood serum in relation to viral load in the lungs of BALB/c mice with pneumonia caused by influenza virus A/Aichi/2/68 (H3N2). Tilorone was administered per os in doses of 40, 150, and 540 μg per mouse 6, 30, and 78 h postinfection, which simulated the drug regimen used in the clinic for the treatment of influenza and acute respiratory viral infections in Russia and post-Soviet countries. Tilorone reduced viral load with the maximum amplitude (2-3 lg) after 1-2 administrations. The results of studying the dynamics of the cytokine levels in the infected animals in general support the previous hypothesis that, in repeated dosing, tilorone enhances the IFN response (compensates for its deficiency) at the early stages of acute respiratory viral infections and suppresses (damps) excessive production of IFN and proinflammatory cytokines at the later stages.

Comparative periodontoprotective effectiveness of diosmin or qvercetin in rats which received hormonal contraceptive

Aim: Determine periodontoprotective effectiveness of bioflavonoides diosmin and quercetin after introducing hormonal contraceptive. Methods: The rats received contraceptive (estradiol+drospirenon) during 30 days. Preparation of diosmin (“Normoven”) introduced per os in dose 84 mg/kg. Preparation of quercetin (“Quertulin”) introduced per os in dose 8 mg/kg. The activities of elastase and lysozyme were determined in gum and serum, the activities of alkaline (AlPh) and acid (AcPh) phosphatases, the contents of calcium and protein were determined in periodontal bone. The degree of bone atrophy of alveolar outgrowth was determined. Results: Was established that the introduction of the contraceptive decreased the mineralizing activity of the bone and increased the degree of atrophy of alveolar outgrowth. Simultaneous introduction of the bioflavonoides stimulated mineralizing activity and reduced the degree of atrophy of alveolar bone. Quercetin was more effective. Conclusion: Bioflavonoides have periodontoprotective activity after using hormonal contraceptive.

Permeability of the Blood-Brain Barrier for Dilept and Its Active Metabolite

Experiments on rats with measurements by HPLC-MS/MS showed that antipsychotic preparation dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) administered per os in doses of 40 and 200 mg/kg crossed the blood-brain barrier and was detected in rat brain (unchanged drug and its active metabolite N-caproyl-L-prolyl-L-tyrosine). The brain/plasma distribution coefficient for dilept was 2.0, for metabolite 0.5. No dose-concentration relationship was found, presumably because of the high dose of the drug transported from the blood to the brain not only by free diffusion, but also with participation of active carriers, whose number was limited.

Bacterial translocation from the gastrointestinal tract in healthy and injured rats

To study the phenomenon of asymptomatic penetration of bacteria from the gastrointestinal tract into various tissues of healthy rats and rats with skin wounds and closed fractures at different doses and with different species of bacteria. Healthy rats and rats with full-thickness skin wounds and closed femoral fractures were given varying doses of radiolabeled bacteria (S. aureus 209P or B. subtilis 534) per os in doses of up to 1010 bacteria per 1kg of body mass. Six hours later, these animals were euthanised and, together with blood smears, tissue samples of liver, spleen, stomach, small and large intestine, lung, hypothalamus, posterior pituitary gland, epinephros and skin and muscle from the wound site were subjected to bacteriological and histological analysis. In total, 99 rats were used for the experiments. Viable bacteria were found to systemically penetrate into the tissues of the internal organs in 45 healthy animals, 27 rats with incisions and 27 rats with fractures. In healthy animals, viable bacteria mostly accumulated in the stomach wall, the mucous membranes of the small intestine, the mesenteric lymph nodes and in the spleen and liver. Translocation was registered in uninjured animals receiving 1x106 and more bacteria per 1kg of rat's weight and in injured rats receiving 1x104 bacteria and more. Bacteria penetrated the local tissues at both wound sites (skin wounds and fracture sites). Bacterial translocation is a protective mechanism that gives the immune system constant contact with external antigens, although it can contribute to the spreading of infection in an organism. In healthy animals, small amounts of bacteria penetrate systemically from the tract and small intestine into the tissues of the spleen and liver. During injury, translocated bacteria also appear at the focus of injury. None.

The hypersensitivity of rabbits to the tetracyclines

It has been established that rabbits possess an increased sensitivity to antibiotics of the tetracycline group. On administering chlortetracycline, tetracycline, or oxytetracycline to rabbits per os in doses of from 5 to 50 mg/kg per day the majority of the animals died within 2 weeks after initiation of the treatment, with phenomena of increasing apathy, anorexia, weight reduction and profuse diarrhea.