A study of osteoprotective effect of l-arginine, l-norvaline and rosuvastatin on a model of hypoestrogen-induced  osteoporosis in rats

Гудырев, О. С.; Сергеевич, Гудырев Олег; Файтельсон, А В; Владимирович, Файтельсон Александр; Sobolev, Mikhail S.; Сергеевич, Соболев Михаил; Pokrovskiy, Mikhail V.; Владимирович, Покровский Михаил; Pokrovskaya, T. G.; Григорьевна, Покровская Татьяна; Корокин, М. В.; Викторович, Корокин Михаил; Povetka, Elena E.; Евгеньевна, Поветка Елена; Miller, E; Сергеевич, Миллер Эдуард; Солдатов, Владислав О.; Олегович, Солдатов Владислав

doi:10.23888/pavlovj2019273325-332

Cited by 4 publications

(1 citation statement)

References 15 publications

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“…The development of generalized osteoporosis was assessed eight weeks (on day 57) after ovariectomy (Gudyrev et al 2019). The following groups were included in the design of the experiment: sham-operated animals (daily oral administration of saline); control group, simulating bilateral ovariectomy (OV); OV + LHT 21-16 at a dose of 50 mg/kg; OV + LHT 21-18 at a dose of 50 mg/kg; OV+ composition №1 at a dose of 50 mg/ kg); OV + alendronic acid (Alendronate) at a dose of 2.5 Each experimental group included 10 animals (Fig.…”

Section: Experimental Animalsmentioning

confidence: 99%

Method for obtaining supramolecular complex based on 3-ohypyridine derivatives and its application for correction of osteoporosis

Trunov

2023

RRP

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Introduction: Currently, there are no safe and ideal medicines for the prevention and treatment of oophorectomy-induced osteoporosis. The development of an effective pharmacotherapy for hypoestrogen-induced osteoporosis is an important task of pharmacology. Materials and Methods: A new supramolecular complex (composition №1) was obtained on the basis of 3-hydroxypyridine derivatives: 2-ethyl-6-methyl-3-hydroxypyridinium 3-pyridinocarbonoate and 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate in a ratio of 1:3 by topochemical synthesis. The study of the osteoprotective activity of the supramolecular complex at a dose of 50 mg/kg was performed on 60 white female rats of the Wistar line on a model of hypoestrogen-induced osteoporosis. The effectiveness of the osteoprotective activity of the complex was evaluated on the 57th day of the experiment. Results and Discussion: The new supramolecular complex (composition №1) has osteoprotective activity, which is expressed in improving the indicators of X-ray and histomorphological samples. Oral administration of composition №1 at a dose of 50 mg/kg led to an increase in bone density to values of 2.55±0.02 g/cm3, which is 1.3 times higher than in the control group 1.92±0.01 g/cm3 (p≤0.05) and reduce bone resorption by improving cortical and trabecular bone structures. Conclusion: The obtained data characterize the prospects of studying composition №1 for the correction and prevention of hypoestrogen-induced osteoporosis. Graphical Abstract

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Section: Experimental Animalsmentioning

confidence: 99%

Method for obtaining supramolecular complex based on 3-ohypyridine derivatives and its application for correction of osteoporosis

Trunov

2023

RRP

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Analysis of oxidative modification of rat epididymal mitochondrial proteins under normobaric chronic hypoxia and modulation of nitric oxide (II) synthesis

Marsyanova

Zvyagina²,

Petrov³

2022

Kazan Med J

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Background. The molecular mechanism of NO effects in adaptation to hypoxia is of interest as a potential point of application in the therapy of fertility disorders. Aim. To assess the degree of oxidative modification of epididymal mitochondrial proteins during hypoxia under conditions of experimentally modified NO synthesis. Material and methods. Sexually mature rats were divided into four groups of 8 individuals: (1) control (animals without hypoxia); (2) chronic normobaric hypoxia, the animals were kept in a sealed chamber with oxygen reduced to 10% once a day for 14 days; (3) animals with hypoxia were injected with an inhibitor of the synthesis of nitric oxide (II) L-nitroarginine methyl ester at a dose of 25 mg/kg intraperitoneally once a day for 7 days; (4) animals with hypoxia were injected with the substrate for NO synthesis L-arginine at a dose of 500 mg/kg intraperitoneally once a day for 10 days. In the mitochondrial fraction of the head and tail of the epididymis, the activity of superoxide dismutase, the amount of NO metabolites, and the degree of oxidative modification of proteins were evaluated. Statistical analysis was performed using the ShapiroWilk, MannWhitney, and Spearman tests; differences were considered significant at p 0.05. Results. Hypoxia led to an increase in the oxidative modification of proteins in the mitochondria of the head of the epididymis 319.12 [240.98; 363.63] c.u./mg protein relative to control 17.89 [15.31; 27.62] c.u./mg protein, p=0.0009. In the mitochondria of the tail of the epididymis, the oxidation of proteins under the studied conditions was less pronounced. The use of L-nitroarginine methyl ester, as well as L-arginine, led to a decrease in the level of oxidative modification of proteins in the head of the epididymis relative to the hypoxia model 39.89 [29.25; 43.17] and 37.25 [34.91; 40.96] c.u./mg of protein, respectively, p=0.0009. Conclusion. Mitochondrial proteins in the head of the epididymis are more susceptible to oxidative damage during hypoxia; a decrease in the level of NO metabolites under conditions of oxygen deficiency is associated with a decrease in the oxidative modification of mitochondrial proteins.

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Hypoxia-Like Effect of L-Arginine in Seminal Vesicle and Epididymis of Rats

Marsyanova,

Zvyagina

2023

I.P. Pavlov Russian Medical Biological Herald

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INTRODUCTION: The effect of L-arginine on metabolic processes is mediated by nitric oxide (II), whose pool is regulated by several enzymes. In the literature, the mutual influence of oxygen deficit and NO production is described. Besides, both processes can be regulated by exogenous L-arginine. AIM: To evaluate participation of L-arginine in the development of adaptive response to chronic normobaric hypoxia of tissues of reproductive system of male rats and to study its influence on metabolic changes in normoxia. MATERIALS AND METHODS: The experiment was conducted on Wistar stock rats (males, n = 8) which were divided to the following groups: (1) animals receiving L-arginine injections of 500 mg/kg of body weight for 10 days; (2) animals of control group receiving 0.9% NaCl solution; (3) animals subjected to chronic normobaric hypoxia in a hermetic chamber, observed once a day for 14 days until the oxygen concentration in the air decreased by 10%; (4) animals of the control group observed in a ventilated chamber; (5) animals subjected to hypoxia and injections of L-arginine. The material for analysis was the mitochondria and mitochondria-free fraction of the cytoplasm of the seminal vesicles, of the head and tail of the epididymis. The parameters were evaluated photometrically using diagnostic and enzyme immunoassay kits. RESULTS: The animals receiving L-arginine showed increase in the amount of -subunit of hypoxia-induced factor in the cytoplasm of seminal vesicles by 132% (p = 0.01), in the tail of epididymis by 32% (p = 0.02) and reduction in mitochondria by 45% (p = 0.01) and 60% (p = 0,002), respectively, a decrease in succinate levels by 40% (p = 0.005) and 51% (p = 0.0009), an increase in the concentration of lactic acid in the cytoplasm by 194% (p = 0.03) and 253% (p = 0.018), a decrease in cytochrome oxidase activity from 0.96 [0.66; 1.69] RU/mg of protein to 0.27 [0.23; 0.32] (p = 0.0009) and from 1.04 [0.84; 1.33] to 0.26 [0.14; 0.37] (p = 0.003), relative to the control group. The observed changes are characteristic of the state of hypoxia and are explained by the cell switching over to glycolytic pathway of energy production, in contrast to mitochondrial pathway in normoxia. The combined effect of hypoxia and arginine partially enhanced each other's effects. CONCLUSION: L-arginine causes hypoxia-like state in cells through activating -subunit by hypoxia-induced factor, reducing cytochrome oxidase activity, increasing glycolysis, and also partially enhances the effects of chronic normobaric hypoxia.

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A study of osteoprotective effect of l-arginine, l-norvaline and rosuvastatin on a model of hypoestrogen-induced osteoporosis in rats

Cited by 4 publications

References 15 publications

Method for obtaining supramolecular complex based on 3-ohypyridine derivatives and its application for correction of osteoporosis

Method for obtaining supramolecular complex based on 3-ohypyridine derivatives and its application for correction of osteoporosis

Analysis of oxidative modification of rat epididymal mitochondrial proteins under normobaric chronic hypoxia and modulation of nitric oxide (II) synthesis

Hypoxia-Like Effect of L-Arginine in Seminal Vesicle and Epididymis of Rats

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