INTRODUCTION: The study of markers of oxidative stress, metabolites of nitric oxide (II) (NOx) and the balance of carnitine fractions in mitochondria of rat epididymis, permits to evaluate the protective role of L-arginine in experimental hyperhomocysteinemia. AIM: To study the influence of L-arginine on the parameters of energy metabolism, level of NO metabolites, oxidative modification of proteins and balance of carnitine fractions in mitochondria of the head and tail of rat epididymis in hyperhomocysteinemia. MATERIALS AND METHODS: In animals of group 1 (n = 8), severe hyperhomocysteinemia (HHcy) was modeled by administration of methionine suspension at a dose of 1.5 g/kg twice daily for 21 days with addition of 1% methionine in drinking water; group 2 rats (n = 8) received suspension base without methionine; animals of group 3 (n = 8) were daily administered L-arginine solution at a dose of 500 mg/kg intragastrically against the background methionine load from day 11 to day 21; group 4 animals (n = 8) were administered L-arginine solution of at a dose of 500 mg/kg for 10 days; group 5 (n = 8) served as a control for group 4 and received drinking water intragastrically. Concentrations of total homocysteine and NOx were determined in serum. In the mitochondrial fraction of the homogenate of epididymis tissues, the level of oxidatively modified proteins (OMP), the concentration of NOx, lactate and carnitine fractions, the activity of lactate dehydrogenase (LDH), superoxide dismutase (SOD), H+-ATPase, succinate dehydrogenase (SDH) were evaluated. RESULTS: HHcy was accompanied by reduction of the level of NOx in blood serum and mitochondria of epididymis head tissues. In mitochondria of tissues of head and tail of epididymis, a marked reduction of all fractions of carnitine, activity of LDH, H+-ATPase, SDH, increase in the activity of SOD and in the level of OMP were observed. With modeled HHcy, L-arginine reduced the extent of hyperhomocysteinemia, prevented reduction of NOx level in the blood serum and epididymis head and reduced the content of OMP of the epididymis mitochondria. CONCLUSION: L-arginine introduced in combination with methionine, reduces the extent of severity of hyperhomocysteinemia. The positive effect of L-arginine on increase in the concentration of NOx metabolites in blood serum and mitochondria of epididymis in conditions of methionine load was also confirmed. L-arginine exhibits antioxidant properties, reducing the severity of oxidative stress induced by hyperhomocysteinemia. Differences in the adaptive response to oxidative stress of the mitochondria of the head and tail of epididymis were demonstrated.
BACKGROUND: Hypoxia is a factor of development of many diseases, and, among other things, may be the cause of male infertility. The molecular basis of pathogenesis in hypoxia can serve a basis for the development of methods of treatment and correction. AIM: development of a model of chronic normobaric hypoxia in laboratory animals. MATERIALS AND METHODS: The study involved 32 mature male rats of Wistar line of 200–280 g mass. The animals were divided to 2 experimental groups and their control groups. In the first experimental model, a model of acute normobaric hypoxia with hypercapnia was used one time according to the method of M. V. Korableva and P. I. Lukienko (1976) in modification of N. D. Avseenko, in the second — a model of chronic hypoxia according to the method of acute normobaric hypoxic hypoxia with hypercapnia in our modification: the animals were placed in a hermetically closed chamber of 1.2 liter volume connected to the gas analyzer, and stayed there until the content of oxygen in the air decreased to 10%. Animals of the control groups were placed in ventilated chambers. The experiment was performed daily for 14 days. The activity of cytochrome oxidase (CO), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the mitochondrial fraction of seminal vesicles and epididymis was determined. RESULTS: In modeling of acute normobaric hypoxia, the activity of the studied enzymes did not show statistically significant changes. In an experiment with chronic normobaric hypoxia, the activity of SOD and CO was significantly reduced in all the studied tissues, and the activity of LDH — only in the tissues of the epididymis head. CONCLUSION: Changes in the activity of key enzymes of mitochondrial metabolism indicate the adaptation to hypoxia at the cellular and subcellular levels, which proves the effectiveness of the described model for further use in research.
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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