Experimental Hyperhomocysteinemia Research Articles

Protective Effects of L-Arginine on Mitochondria of Rat Epididymis in Hyperhomocysteinemia Induced by Prolonged Methionine Load

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.

Ultrastructural changes in the myocardium of animals under conditions of simulated hyperhomocysteinemia, hyper- and hypothyroidism and their combination

Thyroid hormones have a significant impact on heart function through both genomic and non-genomic effects. Deficiency or excess of thyroid hormones leads to profound changes in the regulation of cardiac function and cardiovascular hemodynamics. The heart is the main target organ for the action of thyroid hormones and in patients with hypo- or hyperthyroidism there are marked changes in the work of the heart. The aim of the work was to establish ultrastructural changes in myocardial components in experimental hyperhomocysteinemia (HHCy) against the background of hyper- and hypothyroidism. Thiolactone HHCy was modelized by administering to animals an exogenous HCy in the form of thiolactone at a dose of 100 mg/kg body weight once a day for 28 days. Hyperthyroidism was modelized by daily administration of L-thyroxine at a dose of 200 μg/kg for the 21 days, hypothyroidism – daily administration of thiamazole at a dose of 10 mg/kg for the 21 days. Individual groups of animals were administered L-thyroxine and thiamazole in parallel with HCy. High levels of HCy adversely affected the walls of myocardial blood vessels. The lumens of hemocapillaries were plethoric, filled with erythrocytes. Changes in endotheliocytes were revealed, and cardiomyocytes contained deformed nuclei. In laboratory animals with hyperthyroidism, an increase in ultrastructural changes in the walls of blood vessels (edema of the walls of hemocapillaries, damaged cristae in mitochondria) were established. In animals that were modeled for hyperthyroidism and HHCy, more significant changes in endotheliocytes were revealed, most of the mitochondria were destroyed. More pronounced alterative changes were revealed in cardiomyocytes. An electron microscopic examination of the myocardium of animals with hypothyroidism showed significant degenerative changes in the ultrastructure of the walls of blood vessels, and hypertrophied mitochondria were also found. The combined influence of hypothyroidism and HHCy caused the most profound disturbances in the ultrastructure of cardiomyocytes and hemocapillaries in comparison with other groups of animals. The integrity of intercellular contacts was impaired, most of the mitochondria of myocytes had destroyed cristae and the outer membrane.

Intensity of Ki-67 protein expression by liver cells in experimental hyperhomocysteinemia in rats

Intensity of Ki-67 protein expression by liver cells in experimental hyperhomocysteinemia in rats

Carnitine Chloride Reduces the Severity of Experimental Hyperhomocysteinemia and Promotes Lactate Utilization by the Mitochondrial Fraction of the Rat Epididymis

Carnitine Chloride Reduces the Severity of Experimental Hyperhomocysteinemia and Promotes Lactate Utilization by the Mitochondrial Fraction of the Rat Epididymis

Effect of NMDA-receptors antagonist on serum lipid level under experimental hyperhomocysteinemia in diabetic hamsters

Background and Aims: Hyperhomocysteinemia is a common condition in a course of diabetes, obesity, metabolic syndrome and atherosclerosis. It is observed hyperstimulation of pancreatic NMDA-receptors by endogenous glutamate under metabolic disorders which intensified by another NMDA-agonist homocysteine, that impairs β-cell glucose-dependent insulin secretion. Insulin signal disorders and chronical hyperglycemia provoke atherogenic dyslipidemia. In current study, we have investigated the effect of NMDA-receptor antagonist memantine on lipids level in diabetic hamsters under experimental hyperhomocysteinemia.

Four Weeks of Aerobic Training Affects Cardiac Tissue Matrix Metalloproteinase, Lactate Dehydrogenase and Malate Dehydrogenase Enzymes Activities, and Hepatorenal Biomarkers in Experimental Hyperhomocysteinemia in Rats.

The aim of this study was to investigate the effect of the application of homocysteine as well as its effect under the condition of aerobic physical activity on the activities of matrix metalloproteinases (MMP), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) in cardiac tissue and on hepato-renal biochemical parameters in sera of rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C: 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.); H: homocysteine 0.45 µmol/g b.w./day s.c.; CPA saline (0.9% NaCl 0.2 mL/day s.c.) and a program of physical activity on a treadmill; and HPA homocysteine (0.45 µmol/g b.w./day s.c.) and a program of physical activity on a treadmill. Subcutaneous injection of substances was applied 2 times a day at intervals of 8 h during the first two weeks of experimental protocol. Hcy level in serum was significantly higher in the HPA group compared to the CPA group (p < 0.05). Levels of glucose, proteins, albumin, and hepatorenal biomarkers were higher in active groups compared with the sedentary group. It was demonstrated that the increased activities of LDH (mainly caused by higher activity of isoform LDH2) and mMDH were found under the condition of homocysteine-treated rats plus aerobic physical activity. Independent application of homocysteine did not lead to these changes. Physical activity leads to activation of MMP-2 isoform and to increased activity of MMP-9 isoform in both homocysteine-treated and control rats.

Carnitine chloride reduces the severity of experimental hyperhomocysteinemia and promotes lactate utilization by mitochondrial fraction of the rat epididymis

Hyperhomocysteinemia is a risk factor for many diseases, including reproductive disorders in men. L-carnitine is used in medical practice to correct impaired bioenergetic conditions; in patients with idiopathic forms of infertility its effects are associated with improvement of the sperm parameters. However, the effect of exogenous L-carnitine on the level of homocysteine in the gonadal tissues, as a risk factor for impaired fertility, has not been investigated yet. The aim of this study was to investigate activity of bioenergetic enzymes in the epididymal mitochondrial fraction, the dynamics of changes in the cytoplasmic and mitochondrial lactate levels and LDH activity, the total carnitine content, as well as the oxidative status of these cells under conditions of oxidative stress caused by hyperhomocysteinemia, and to assess the effect of carnitine chloride on these parameters under conditions of methionine administration to male Wistar rats. Methionine administration to animals for three weeks at a dose of 3 g/kg, resulted in development of the severe forms of hyperhomocysteinemia with serum homocysteine concentrations exceeding 100 μmol/L. This was accompanied by a decrease in the activity of enzymes involved in the bioenergetic processes of the cell: tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) in the epididymal head and tail. The change in lactate metabolism included an increase in its level in both the mitochondrial and cytoplasmic fractions of the epididymal head and mitochondria of the epididymal tail, and also simultaneous statistically significant decrease in LDH activity in the mitochondria and cytoplasm of the epididymal head. In male rats with severe hyperhomocysteinemia, an increase in the activity of mitochondrial SOD accompanied by an increase in the carbonylation of mitochondrial proteins in the head and tail of the epididymis was noted. Modeling of hyperhomocysteinemia under conditions of carnitine chloride of administration led to different reactions of the cells of the studied tissues assayed in the epididymal head and tail homogenate. In the epididymal head, carnitine chloride promoted an increase in the mitochondrial lactate concentration and a decrease in the cytoplasmic lactate concentration, as well as an increase in the LDH activity associated with the mitochondrial fraction. These changes were accompanied by an increase in the activity of H+-ATPase in the epididymal, thus suggesting that carnitine chloride stimulated lactate transport of into the mitochondria and its use as an energy substrate under conditions of oxidative stress caused by hyperhomocysteinemia. In the tail tissues, the changes were protective in nature and were associated with a decrease in the formation of oxidatively modified proteins.

Changes in the histostructure of the lungs of old rats under conditions of persistent hyperhomocysteinemia

To date, homocysteine has been found to be an important biomarker of bronchopulmonary pathology, including COPD. The increase in its concentration in the blood plasma causes the start of free radical processes and the production of reactive oxygen species, which activate lipid peroxidation in lung tissue. In addition, the activation of endoplasmic reticulum stress with increasing homocysteine levels is the main reason for triggering apoptosis of alveolocytes. The aim of the research is to study the features of lungs histostructure in old rats under conditions of hyperhomocysteinemia. The experimental study was performed on 20 white nonlinear old (24-26 months) male rats. During the experiment, the animals were divided into two groups – control and experimental. Simulation of the state of persistent hyperhomocysteinemia was achieved by administering to rats of experimental group thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrally for 60 days. Histological specimens were studied using an SEO CCAN light microscope and photo-documented using a Vision CCD Camera with an image output system from histological specimens. In elderly animals under conditions of experimental hyperhomocysteinemia develop severe destructive-degenerative changes in the lungs. Significant remodeling of the vascular bed, bronchi, inflammatory manifestations, enlargement of dis- and atelectasis and emphysematically altered alveoli of the respiratory lungs, violation of the alveolar walls, with the release of blood cells into the alveolar space and the formation of small diapedetic hemorrhages. The development of perivascular, peribronchial and interstitial sclerosis is characteristic.

The effect of hyperhomocysteinemia on the patterns of electron microscopic changes in the liver of adult rats

One of the important tasks of modern science is to find biochemical markers that would be able to reflect the risks of development and the nature of the course of various diseases, as well as to predict their possible consequences. In recent years, a significant number of compounds that can affect the biochemical profile of the organism have been identified. Homocysteine – a product of methionine metabolism, belongs to one of these markers, and the effects of its influece on the structure and function of various organs are being actively studied by modern researchers. The aim of the study is to find the patterns of electron microscopic changes in the liver structure of adult rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear mature male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the liver of rats was performed using an electron microscope PEM-125K. In adult rats with experimental hyperhomocysteinemia at the ultrastructural level, dystrophic and destructive changes in hepatocytes, endotheliocytes in the walls of sinusoids and Kupffer cells were found. These changes were more pronounced than in young rats with experimental hyperhomocysteinemia. Revealed structural changes in decompensation (depletion) of mitochondria – fewer number of cristae and enlightened matrix. In contrast to young rats, adult rats with hyperhomocysteinemia in the perisinusoidal spaces showed elongated Ito cells, a significant proportion of the cytoplasm is occupied by the Golgi complex and granular endoplasmic reticulum tanks, indicating protein synthesis for export. In Ito cells, the content of fat droplets, which are located on opposite poles of cells, is reduced. This morphological picture manifests the transformation of Ito cells into fibroblasts.

Submicroscopic changes in the liver of young rats with hyperhomocysteinemia

To date, it has been established that hyperhomocysteinemia plays a significant role in the development and progression of many diseases. The accumulation of homocysteine occurs due to a violation of the relationship between its production and excretion from the body. The liver plays an important role in the metabolism of homocysteine, because it undergoes most of the reactions of its transmethylation, and, therefore, it is the first to be adversely affected. The aim of the study is to identify the features of electron microscopic changes in the liver structure of young rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear young (1-2 months) male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats the experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the liver of rats was performed using an electron microscope PEM-125K. It was found that the introduction of thiolactone homocysteine at a dose of 200 mg/kg in rats led to the development of degenerative changes in hepatocytes. Changes in the structure of liver cells manifested themselves in the form of edema of the cytoplasm and mitochondria, destruction of mitochondrial cristae, dilation of the tubules of the granular endoplasmic reticulum and tanks of the Golgi complex. The activity of fat-accumulating liver cells and stellate macrophages is characteristically. In the lumens of the sinusoidal capillaries found sweeter shaped blood elements, the cytoplasm of endothelial cells had signs of edema. Thus, in experimental hyperhomocysteinemia revealed changes at the ultrastructural level in all structural components of the liver of young rats. The identified changes are compensatory-adaptive in nature and are reversible.

Features of electron microscopic changes in the liver of rats aged 24-26 months under conditions of hyperhomocysteinemia

Disruption of the metabolism of the essential amino acid methionine causes the syndrome of hyperhomocysteinemia. This pathological condition is associated with the risk of developing a number of diseases, including chronic liver disease. The mechanisms of liver tissue damage in hyperhomocysteinemia remain poorly understood and require more detailed study. The aim of the study is to establish the features of submicroscopic changes in the liver structure of old rats with hyperhomocysteinemia. The experimental study was performed on 22 white nonlinear old (24-26 months) male rats, which were divided into a control group and an experimental group. A model of persistent hyperhomocysteinemia was created by administering to rats of experimental group of thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. The study of ultrastructural changes in the lungs of rats was performed using an electron microscope PEM-125K. At experimental hyperhomocysteinemia in a liver of old rats there are changes in all structural components. Mitochondrial destruction and edema were observed in the vascular endothelium. Organelles have an enlightened matrix, a reduced number of cristae. A significant content of destructively altered mitochondria in endothelial cells indicates a failure of adaptation mechanisms. Erythrocyte sludges are observed in the lumens of the sinusoids. The number of fat-accumulating cells decreases, which indicates their transformation into fibroblasts and leads to the growth of collagen fibers, expansion of the sinusoidal spaces and the development of stromal fibrosis.

Neurotrophic factors and inflammatory cytokines in the mother-placenta-fetus system in experimental hyperhomocysteinemia

An essential aspect of metabolic imbalance of L-homocysteine and its accumulation in blood (hyperhomocysteinemia) is its aggravating effect in pregnancy. However, little is known about the effects of maternal increased L-homocysteine levels on brain development of fetuses. In the development of the fetus, accompanied by changes in metabolism in the placenta, an important role belongs to neurotrophic factors and apoptosis. This study investigated the effects of chronic L-methionine administration on some parameters of inflammation and on neurotrophic factor levels in the brain of embryos, as well as in the placenta and serum of pregnant rats. The observed disturbances can be resulted from both a direct impact of L-homocysteine and its metabolites on the fetal CNS, and hyperhomocysteinemia-caused changes in normal state of the placenta.

Оцінка стоматологічного статусу у щурів при експериментальній гіпергомоцистеїнемії та її корекції холіном і вітаміном D

Оцінка стоматологічного статусу у щурів при експериментальній гіпергомоцистеїнемії та її корекції холіном і вітаміном D

The effect of arginine on the activity and compartmentalization of lysosomal cysteine proteinases of parenchymatous organs in oxidative stress on the background of experimental hyperhomocysteinemia

Aim. Evaluation of the effect of arginine on the activity and intracellular distribution of cathepsins B, L, H in liver, kidney and lung tissue in experimental hyperhomocysteinemia and developing on its background oxidative damage of proteins.&#x0D; Materials and Methods. Hyperhomocysteinemia in male rats of the Wistar line was formed by daily oral administration of a suspension of methionine at a dose of 1.5 g/kg 2 times a day for 21 days, to study the action of arginine the substance was used orally from 12 to 21 days of methionine administration at a dose of 500 mg/kg. In tissue homogenates measurements were carried out in cytoplasmic and lysosomal fractions. The state of oxidative modification of proteins was evaluated by analysis of the absorption spectrum of carbonyl derivatives, the activity of cathepsins B, L, H was determined by spectrofluorometric method, the activity of acid phosphatase – by the unified method «at the end point».&#x0D; Results. In the cytoplasmic (nonsedimentary) fraction of the liver and kidney reduced activity of cathepsin L (in both tissues), cathepsin B (in the kidney), cathepsin H (in the liver) was found on the background of the increase in the products of proteins oxidative modification in experimental hyperhomocysteinemia. The introduction of arginine in experimental hyperhomocysteinemia completely eliminated the manifestations of oxidative damage of proteins, partially correcting the activity of enzymes: there was an increase in the activity in non sedimentary (cytoplasmic) fraction due to intracellular redistribution of enzymes. There is found inverse correlation between the content of oxidative carbonylation products of proteins and the activity of cathepsins in the non sedimentary fraction, as well as the proportion of their non sedimentary activity.&#x0D; Conclusions. 1. Arginine at a dose of 500 mg/kg at a 10day administration completely corrects the increase in the products of oxidative protein carbonylation that develops in experimental hyperhomocysteinemia. 2. Under the influence of arginine there is an increase in the reduced due to isolated hyperhomocysteinemia activity of cathepsins B, L, H in the cytoplasmic fraction of the liver and kidney due to intracellular redistribution of enzymes. 3. Arginine administration causes nonselective increase of the lysosomal membrane permeability, and as a result, changes in the compartmentalization of lysosomal cysteine proteases. 4. The inverse correlation of the level of protein oxidative modification products with the activity of cathepsins in cytoplasmic (nonsedimentary) fractions, and the proportions of their nonsedimentary activity, suggesting the presence of contribution of changes in the compartmentalization of lysosomal cysteine proteinases in developing under the action of arginine compensation of oxidative stress in experimental hyperhomocysteinemia.

The effect of arginine on the activity and compartmentalization of lysosomal cysteine proteinases of parenchymatous organs in oxidative stress on the background of experimental hyperhomocysteinemia

Aim. Evaluation of the effect of arginine on the activity and intracellular distribution of cathepsins B, L, H in liver, kidney and lung tissue in experimental hyperhomocysteinemia and developing on its background oxidative damage of proteins.&#x0D; Materials and Methods. Hyperhomocysteinemia in male rats of the Wistar line was formed by daily oral administration of a suspension of methionine at a dose of 1.5 g/kg 2 times a day for 21 days, to study the action of arginine the substance was used orally from 12 to 21 days of methionine administration at a dose of 500 mg/kg. In tissue homogenates measurements were carried out in cytoplasmic and lysosomal fractions. The state of oxidative modification of proteins was evaluated by analysis of the absorption spectrum of carbonyl derivatives, the activity of cathepsins B, L, H was determined by spectrofluorometric method, the activity of acid phosphatase – by the unified method «at the end point».&#x0D; Results. In the cytoplasmic (nonsedimentary) fraction of the liver and kidney reduced activity of cathepsin L (in both tissues), cathepsin B (in the kidney), cathepsin H (in the liver) was found on the background of the increase in the products of proteins oxidative modification in experimental hyperhomocysteinemia. The introduction of arginine in experimental hyperhomocysteinemia completely eliminated the manifestations of oxidative damage of proteins, partially correcting the activity of enzymes: there was an increase in the activity in non sedimentary (cytoplasmic) fraction due to intracellular redistribution of enzymes. There is found inverse correlation between the content of oxidative carbonylation products of proteins and the activity of cathepsins in the non sedimentary fraction, as well as the proportion of their non sedimentary activity.&#x0D; Conclusions. 1. Arginine at a dose of 500 mg/kg at a 10day administration completely corrects the increase in the products of oxidative protein carbonylation that develops in experimental hyperhomocysteinemia. 2. Under the influence of arginine there is an increase in the reduced due to isolated hyperhomocysteinemia activity of cathepsins B, L, H in the cytoplasmic fraction of the liver and kidney due to intracellular redistribution of enzymes. 3. Arginine administration causes nonselective increase of the lysosomal membrane permeability, and as a result, changes in the compartmentalization of lysosomal cysteine proteases. 4. The inverse correlation of the level of protein oxidative modification products with the activity of cathepsins in cytoplasmic (nonsedimentary) fractions, and the proportions of their nonsedimentary activity, suggesting the presence of contribution of changes in the compartmentalization of lysosomal cysteine proteinases in developing under the action of arginine compensation of oxidative stress in experimental hyperhomocysteinemia.

СТАТЕВІ ВІДМІННОСТІ ВПЛИВУ ГІПЕРГОМОЦИСТЕЇНЕМІЇ НА МЕТАБОЛІЗМ ГІДРОГЕН СУЛЬФІДУ В СЕРЦЕВО-СУДИННІЙ СИСТЕМІ

Гіпергомоцистеїнемія є відомим та незалежним фактором ризику патології серця та судин. Показано, що за цього патологічного стану зменшується рівень гідроген сульфіду – біологічноактивної речовини, що причетна до регуляції тонусу судин, скоротливості міокарда. Однак залишається невивченим існування статевих відмінностей впливу гіпергомоцистеїнемії на метаболізм гідроген сульфіду в серцево-судинній системі.Мета дослідження – вплив експериментальної гіпергомоцистеїнемії на вміст гідроген сульфіду та його обмін у міокарді та аорті щурів різної статі.Матеріали і методи. Досліди проведено на 40 білих лабораторних щурах обох статей масою 220–280 г. Модель тривалої гіпергомоцистеїнемії створювали шляхом введення тіолактону D, L-гомоцистеїну інтрагастрально в дозі 100 мг/кг маси на 1% розчині крохмалю 1 раз на добу протягом 28 діб. У роботі визначали вміст гідроген сульфіду в міокарді та аорті, швидкість утилізації гідроген сульфіду в міокарді, а також активність ферментів цистатіонін-γ-ліази, цистеїнамінотрансферази, тіосульфатдитіолсульфідтрансферази, сульфітоксидази в міокарді та аорті.Результати досліджень та їх обговорення. Гіпергомоцистеїнемія супроводжується стать-специфічними змінами вмісту гідроген сульфіду в міокарді та аорті щурів: зниження рівня гідроген сульфіду в самців та самок становить відповідно (31,4–43,3) % та (20,0-25,1) % (р&lt;0,05) порівняно з контролем. Тривале введення тіолактону гомоцистеїну викликає більш істотні порушення метаболізму гідроген сульфіду в міокарді та аорті в самців: збільшення швидкості утилізації гідроген сульфіду становить 36,5 % (проти 22,5 % у самок, р&lt;0,05), зменшення активності H2S-синтезуючих ензимів становить 28,3–49,8 % (проти 17,1–36,8 % у самок, р&lt;0,05) порівняно з контролем.Висновки. Ввведення тіолактону гомоцистеїну викликає стать-специфічні зміни метаболізму гідроген сульфіду в міокарді та аорті. Показано, що у самців реєструється більш виразне зменшення вмісту гідроген сульфіду, активності Н2S-синтезуючих ензимів та мітохондріальної сульфітоксидази, а також збільшення швидкості утилізації екзогенного гідроген сульфіду в серцево-судинній системі порівняно з контролем.

Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia

Hyperhomocysteinemia is a risk factor for many human diseases, including pulmonary pathologies. In this context much interest attracts secondary mitochondrial dysfunction, which is an important link in pathogenesis of diseases associated with hyperhomocysteinemia. The study was conducted using male Wistar rats. It was found that under conditions of severe hyperhomocysteinemia caused by administration of methionine, homocysteine was accumulated in lung mitochondria thus suggesting a direct toxic effect on these organelles. However, we have not observed any significant changes in the activity of mitochondrial enzymes involved in tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) and of cytoplasmic lactate dehydrogenase. Also there was no accumulation of lactic acid in the cytoplasm. Animals with severe hyperhomocysteinemia had higher levels of lung mitochondrial protein carbonylation, decreased reserve-adaptive capacity, and increased superoxide dismutase activity. These results indicate that severe hyperhomocysteinemia causes development of oxidative stress in lung mitochondria, which is compensated by activation of antioxidant protection. These changes were accompanied by a decrease in the concentration of mitochondrial nitric oxide metabolites. Introduction to animals a nonselective NO-synthase inhibitor L-NAME caused similar enhancement of mitochondrial protein carbonylation. It demonstrates importance of reducing bioavailability of nitric oxide, which is an antioxidant in physiological concentrations, in the development of oxidative stress in lung mitochondria during hyperhomocysteinemia. Key words: hyperhomocysteinemia, nitric oxide, lung, oxidative stress, mitochondria.

EFFECTS OF ISOLATED VITAMIN B6 SUPPLEMENTATION ON OXIDATIVE STRESS AND HEART FUNCTION PARAMETERS IN EXPERIMENTAL HYPERHOMOCYSTEINEMIA

Introduction : The purpose of this study was to investigate the effects of isolated vitamin B 6 (VB 6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB 6, HcyT, and HB 6 ). On the 30th day of treatment, two groups were supplemented with VB 6 in the drinking water (groups: CB 6 and HB 6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB 6 group. Additionally, GST immunocontent was enhanced (51%) in the HB 6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB 6 group compared to the CB 6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB 6 group. Ejection fraction (EF) was improved in the HB 6 group compared to the HcyT group. E/A ratio was enhanced in the HB 6 group compared to the CB 6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB 6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters. Keywords: Homocysteine; oxidative stress; vitamin B 6.

On the role of biogenic amines and reactive oxygen species in the disruption of the hypothalamic regulation of reproductive function in xenobiotic-induced and experimental hyperhomocysteinemia

This review describes the role of biogenic amines in the hypothalamic regulation of ovarian cycles in female rats. The mechanisms of action of industrial xenobiotics and experimental hyperhomocysteinemia, which induces premature aging of the reproductive function, are discussed. The point of view that the damaging action of reactive oxygen species is the basis of the unified response of hypothalamic regulation of reproductive cycles to external and internal neurotoxic impacts is substantiated. We describe the involvement of melatonin and short regulatory peptides in antioxidant protection of the reproductive system during aging.

Lymphocyte Subpopulations and Cytokine Levels in Experimental Hyperhomocysteinemia.

Moderate exogenous hyperhomocysteinemia is associated with an increase in lymphocyte count (mainly at the expense of cytotoxic T cells), a 2-fold drop of the immunoregulatory index, and increase in TNF-α, IFN-γ, and IL-17α concentrations in the serum and in mononuclear cells. Homocysteine concentration in the mononuclears remains unchanged.