[Effects of soybean isoflavones on the energy metabolism of swimming mice].

OBJECTIVE: To establish an animal model for loaded swimming, so as to investigate the energy metabolism effects of soybean isoflavones (SI) on swimming mice. METHODS: Thirty male Kunming mice were randomly divided into three groups:normal control, swimming group, and swimming+SI group. The normal control group mice were fed a basic AIN-93M diet, the SI groups were supplied with soybean isoflavones(4 g/kg).Two weeks later, the mice were forced to swim for an hour,and then all the mice were killed, the samples of blood, liver and muscles of hind were collected.The serum contents of lactic acid(Lac), the activities of lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), creatine kinase (CK) and ATPase were measured. RESULTS: Compared with normal control,the serum content of Lac was significantly improved in the group of the swimming control and SI(P<0.05),the activity of LDH in the serum was obviously improved in the group of the swimming control and SI, and the activity of CK and SDH were both significantly improved in the group of the swimming control and SI except the activity of SDH in the liver of the group SI; compared with the swimming control,the serum contents of Lac,the activities of LDH, ATPase, SDH, CK were obviously improved(P<0.05). CONCLUSIONS: Soybean isoflavones can improve the energy metabolism,antioxidant capacity of the swimming mice.

[Effect of occupational exposure to toluene diisocyanate on workers' health].

OBJECTIVE: To investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health. METHODS: A total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis. RESULTS: The exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P <0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P<0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P <0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P <0.05; r=-0.239, P <0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices. CONCLUSION: TDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.

Effect of Food Load on Activities of Enzymes of the Main Metabolic Pathways in Blood Lymphocytes in Girls with Different Anthropometric Parameters.

Changes in enzyme activities reflecting functioning of the basic metabolic pathways in cells (Krebs cycle, glycolysis, pentose phosphate pathway) were evaluated in blood lymphocytes of girls of different somatotypes with different body composition under conditions of food load. A common regularity was found: a decrease in succinate dehydrogenase activity after meal in girls of all somatotypes. Specific features of individual somatotypes were also revealed. Only girls of athletic somatotype showed increased lactate dehydrogenase level after food load. Activity of glucose-6-phosphate dehydrogenase increased (more than twice) after food load only in girls of euryplastic somatotype. This somatotype is characterized by maximum values of fat and other components of the body. Glucose-6-phosphate dehydrogenase is the first enzyme of the pentose phosphate pathway; activation of this pathway accompanies enhancement of synthetic processes, including lipid synthesis. This can contribute to accumulation of the fat component (and other components) due to redistribution of substrate flows between metabolic pathways.

Chrono- and Immunocorrection of Inflammatory Disorders of Internal Reproductive Organs in Women of Reproductive Age.

We compared the effectiveness of immunomodulators used in the treatment of patients with chronic salpingitis and oophoritis with or without changes in succinate dehydrogenase (SDH) activity in blood lymphocytes at incubation with the drug. Diurnal variations in individual reaction of SDH in blood lymphocytes to thymalin or ridostin were revealed. In the groups of women receiving ridostin or thymalin during the reaction of lymphocyte SDH to it, improvement of clinical laboratory and immunological parameters was observed in the majority of the patients and no effect was found in a lesser group of patients than in the groups treated with drugs during the absence of lymphocyte SDH reaction thereto. The timing of the presence of SDH reaction to drugs in the immunocompetent cells makes it possible to set the optimal daily regime of their application and to select a drug that would be most effective in each particular case.

[Effects of Light Near-Infrared Radiation on Rats Assessed by Succinate Dehydrogenase Activity in Lymphocytes on Blood Smears].

Biological effects of light near infrared radiation (850 nm), with modulation acoustic frequency of 101 Hz, was studied. The study was conducted on rats, the effect was recorded by succinate dehydrogenase activity in lymphocytes on the blood smear after administration of the activating dose of adrenaline, which simulates the state of the organism in the early stages of the pathogenic effects (stress). A pronounced regulating effect of infrared radiation on the activity of succinate dehydrogenase in animals activated by adrenaline was shown. Infrared radiation has a normalizing effect reducing the degree of inhibition or activation of the enzyme induced by adrenaline and had no effect on the control animals. Thus, by modulating the activity of succinate dehydrogenase infrared radiation regulates energy production in the mitochondria supported by the most powerful oxidation substrate--succinic acid, which is especially pronounced under stress.

[Peculiarities of clinical and metabolic adaptation of newborns extracted by repeated cesarean section].

The aim of the article was to study the cellular adaptation of newborn extracted by repeated cesarean section (RCS). The study of functional activity of monocytes was conducted. The activity of succinate dehydrogenase (SDG) and glutamate dehydrogenase (GDG), acid phosphatase (AP) and myeloperoxidase (MPO) of 120 newborns, extracted by RCS was determined by means of cytochemical methods. Analyses were performed in the dynamics of the neonatal period on 1-3, 5-7, 28-30 days of life of the infants. It was found that neonatal exposure to PCB on the cell membrane and intracellular structures is accompanied by high activity of the lysosomal acid phosphatase marker and low activity of mitochondrial enzymes SDG and GDG. Reduced activity of MPO from the 1st day of life and the lack of normalization of this index on the 28-30 days of life shows the exhaustion of mechanisms that determine the margin of safety of adaptive responses.

Effects of acetaldehyde and L-carnitine on morphology and enzyme activity of myocardial mitochondria in rats.

This study aimed to investigate the effects of acetaldehyde (AA) and L-carnitine (LC) on morphology and enzyme activity of myocardial mitochondria in rats. Sixty-five Wistar rats were randomly divided into 4 groups: the control group (n = 20), the AA low-dose group (n = 15), the AA high-dose group (n = 15) and the AA + LC group (n = 15). Different doses (110 mg/kg and 220 mg/kg) AA was injected intraperitoneally once a day for 4 weeks. After 4 weeks administration, transmission electron microscope (TEM) observation of morphology of rat myocardial mitochondria was performed. Serum levels of succinate dehydrogenase (SDH), superoxide dismutase (SOD), malondialdehyde (MDA) and cardiac troponin I (cTnI) were detected to evaluate mitochondrial enzymes activities. Light micrograph of rat myocardiocytes in the control group showing normal architecture of myocytes. The numerical density and number of mitochondria in both low-dose and high-dose AA groups were lower than that of the control group. After administration of LC, the rats in the AA + LC group showed an obvious increase in the numerical density and number of mitochondria. TEM showed that both low-dose and high-dose AA could induce myocardial mitochondrial damage in rats in a dose-dependent manner, such as mitochondrial swelling, disruptions of crest and membrane, mitochondrial deficiency. The degree of mitochondrial damage of the AA + LC group was significantly decreased after administration of LC. Our results showed that serum levels of SDH and SOD in the AA + LC and control groups were also higher than those of the low-dose and high-dose AA groups; while the MDA level in the AA + LC and control groups were lower than that of the low-dose and high-dose AA groups. The low-dose AA, high-dose AA and AA + LC groups exhibited a higher level of serum cTnI than that of the control group. However, there was no significant difference in serum cTnI level among the low-dose AA, high-dose AA and AA + LC groups. Our findings indicate that AA may lead to myocardial mitochondrial damage and the induction of enzyme activity in rats, while administration of LC could alleviate AA-related damage of rat myocardial mitochondria.

Lack of liver injury in Wistar rats treated with the combination of isoniazid and rifampicin.

Isoniazid (INH) can cause serious idiosyncratic liver injury. An animal model would greatly facilitate mechanistic studies, but it is essential that the mechanism in the model be similar to the liver injury that can occur in humans. We attempted to replicate a previous study in which Wistar rats treated with INH and rifampicin (RMP) developed liver injury, which was promising because of its delayed onset similar to the liver injury that can occur in humans. Wistar rats were treated with either a high dose of INH (150 mg/kg/day) or a combination of INH and RMP (75 mg/kg/day and 50 mg/kg/day, respectively) for up to 4 weeks. However, we did not observe any liver injury or evidence of an inflammatory infiltrate as had been reported; rather, we observed an increase in CTLA4-positive cells in the cervical lymph nodes as well as a decrease in serum CXCL1 and MCP-1. In short, we were unable to reproduce a previously reported model of delayed onset INH-induced liver injury in Wistar rats.

[SODIUM SUCCINATE AS METHOD OF INTENSIVE CARE OPTIMIZATION OF NEWBORNS' MULTIORGAN FAILURE SYNDROM].

With the aim of ascertainment of pathogenesis of newborns' multiorgan failure syndrom it was made a research of lactat, pyruvate, urea containing and succinatedehydrogenase activity of newborns venous blood with sequences to perinatal infection and perinatal asphyxia. Was set the reliable increase of concentration of lactat, pyruvate and their ratio, that demonstrates the presence of cellular energy deficit. There was direct correlation communication between concentrations of pyruvate and urea. In the application of sodium succinate to reduce the content of lactic and pyruvic acids, their ratio, increase the activity of succinatedehydrogenase, which is evidence of improved mitochondrial energy production, as well as reduces the frequency of gastrointestinal insufficiency implementation.

[The energetic metabolism in newborns in normal conditions and under development of disorders of adaptation in early postnatal period].

The article deals with the prospective complex approach to laboratory analysis of energetic metabolism under states of newborns. The approach provides simultaneous detection of content of main energy substrates, activity of adenosinetriphosphatases and succinate dehydrogenases in umbilical blood, characterized by high sensitivity to hypoxia.

[State of succinate dehydrogenase in the organism--"unbalanced" or hyperactive].

Through the use of the original cytobiochemical method to study oxidation in mitochondria, preserving their native organization in network within cells in a blood smear, we revealed hyperactive state of succinate dehydrogenase, which is realized in the organism under physiological stress. It is consistent with the view of the non-equilibrium state of enzymes during activity. The mechanism of the succinate dehydrogenase hyperactivity moderation is based on the full functioning of alpha-ketoglutarate dehydrogenase, supported by oxidation of isocitric acid.

Effect of eccentric training on mitochondrial function and oxidative stress in the skeletal muscle of rats.

The objective of the present study was to investigate the effects of eccentric training on the activity of mitochondrial respiratory chain enzymes, oxidative stress, muscle damage, and inflammation of skeletal muscle. Eighteen male mice (CF1) weighing 30-35 g were randomly divided into 3 groups (N = 6): untrained, trained eccentric running (16°; TER), and trained running (0°) (TR), and were submitted to an 8-week training program. TER increased muscle oxidative capacity (succinate dehydrogenase and complexes I and II) in a manner similar to TR, and TER did not decrease oxidative damage (xylenol and creatine phosphate) but increased antioxidant enzyme activity (superoxide dismutase and catalase) similar to TR. Muscle damage (creatine kinase) and inflammation (myeloperoxidase) were not reduced by TER. In conclusion, we suggest that TER improves mitochondrial function but does not reduce oxidative stress, muscle damage, or inflammation induced by eccentric contractions.

Effect of eccentric training on mitochondrial function and oxidative stress in the skeletal muscle of rats

The objective of the present study was to investigate the effects of eccentric training on the activity of mitochondrial respiratory chain enzymes, oxidative stress, muscle damage, and inflammation of skeletal muscle. Eighteen male mice (CF1) weighing 30-35 g were randomly divided into 3 groups (N = 6): untrained, trained eccentric running (16°; TER), and trained running (0°) (TR), and were submitted to an 8-week training program. TER increased muscle oxidative capacity (succinate dehydrogenase and complexes I and II) in a manner similar to TR, and TER did not decrease oxidative damage (xylenol and creatine phosphate) but increased antioxidant enzyme activity (superoxide dismutase and catalase) similar to TR. Muscle damage (creatine kinase) and inflammation (myeloperoxidase) were not reduced by TER. In conclusion, we suggest that TER improves mitochondrial function but does not reduce oxidative stress, muscle damage, or inflammation induced by eccentric contractions.

[Stressogenic exposure of local vibration to energetic metabolism of the heart, liver and kidney of rats].

The purpose of the paper was to study the activity of energy producing system of the rabbit myocardium, liver and kidneys after exposure to local vibration during 7 days. The energy dependent reactions of native mitochondria were investigated by means of polarographic method using dark closed membrane electrode. The intensivity ofoxydative processes was assessed according to activity of the lymphocyte succinate dehydrogenase and catalase of the blood. The energy producing system of the tissues studied was shown to be involved in response reaction of the organism on vibration exposure. In that case we observed the formation of the second phase ofbioenergy hypoxia in the myocardium and kidneys and the first phase ofhypoxia in the liver.

[The protective effect of autologous plasma against the development of oxidative stress in UV-irradiated lymphocytes of peripheral blood of donors].

The influence of UV-light (240-390 nm) at the dozes of 151 and 755 J/m2 on the intensity of processes of the lipid peroxidation, activity of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), cytochrome c oxidase and the level of the energy supply of donors' blood lymphocytes in the absence and presence of autologous plasma was investigated. It was shown that during the incubation of native and UV-irradiated lymphocytes, autologous plasma reduces the intensity of lipid peroxidation, thus protecting cells from oxidative stress. As a result, the endocellular level of ATP is restored in UV-irradiated lymphocytes (during the daily incubation), which reflects the intensification of the adaptive ability of cells in the presence of autologous plasma.

Reduced NADH coenzyme Q dehydrogenase activity in platelets of Parkinson's disease, but not Parkinson plus patients, from an Indian population.

The observation of decline in mitochondrial electron transport chain function, specifically at complex I, in patients with Parkinson's disease (PD) has been reported by several groups. This study investigates whether a defect of mitochondrial function is present in the platelets of PD patients from an Indian population. We found that the NADH dehydrogenase activity in the platelets of PD patients is lower than that in healthy age- and gender-matched controls, while the succinate dehydrogenase activity was similar in both groups. Furthermore, there was no change in either of the activities in patients with Parkinson plus syndrome or atypical parkinsonism. This is the first report indicating a decline in mitochondrial function in the platelets of PD patients from the Indian population, offering further support to the role of a mitochondrial defect in PD.

Strontium fructose 1,6-diphosphate alleviates early diabetic testopathy by suppressing abnormal testicular matrix metalloproteinase system in streptozocin-treated rats.

OBJECTIVES: Male hypogonadism is frequently associated with testopathy in patients with type 2 diabetes and in middle-aged males. We hypothesized that abnormal matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in testis have large roles to play in male hypogonadism. It has been found in diabetic rats that a novel compound, strontium fructose 1,6-diphosphate (FDP-Sr), with extra high energy supply, could reverse male hypogonadism by normalizing MMP-9 and TIMPs in the testis. We investigated whether FDP-Sr could be promising in treating diabetic testopathy. METHODS: Adult male Sprague-Dawley rats were administered a single dose of streptozocin (65 mg/kg, i.p.) to induce diabetes. The diabetic rats were treated with FDP-Sr in three doses or testosterone propionate in the final four weeks during the eight-week study. KEY FINDINGS: Serum testosterone, activity of marker enzymes, and mRNA of MMPs and TIMPs and protein of MMP-9 in the testis were detected. After eight weeks, the activity of acid phosphatase, lactate dehydrogenase, succinate dehydrogenase and g-glutamyl transpeptidase in testis were significantly decreased (P < 0.01), accompanied by down-regulated mRNA and activity of MMP-2 and MMP-9 (P < 0.01) and upregulated mRNA of TIMP-1 and TIMP-2. Downregulated MMP-9 protein and degenerative changes in histology were predominant in diabetic testis. CONCLUSIONS: FDP-Sr or testosterone propionate significantly normalized expression and activity of the MMPs-TIMPs system to attenuate changes in serum testosterone, marker enzymes and histology in testis. Effects of FDP-Sr were dose-dependent and comparable with those of testosterone propionate. By supplying extra energy, FDP-Sr could be promising in treating diabetic testopathy by normalizing abnormal MMP-9 and its endogenous inhibitors in testes.

A recurrent stop-codon mutation in succinate dehydrogenase subunit B gene in normal peripheral blood and childhood T-cell acute leukemia.

BACKGROUND: Somatic cytidine mutations in normal mammalian nuclear genes occur during antibody diversification in B lymphocytes and generate an isoform of apolipoprotein B in intestinal cells by RNA editing. Here, I describe that succinate dehydrogenase (SDH; mitochondrial complex II) subunit B gene (SDHB) is somatically mutated at a cytidine residue in normal peripheral blood mononuclear cells (PBMCs) and T-cell acute leukemia. Germ line mutations in the SDHB, SDHC or SDHD genes cause hereditary paraganglioma (PGL) tumors which show constitutive activation of homeostatic mechanisms induced by oxygen deprivation (hypoxia). PRINCIPAL FINDINGS: To determine the prevalence of a mutation identified in the SDHB mRNA, 180 samples are tested. An SDHB stop-codon mutation c.136C>T (R46X) is present in a significant fraction (average = 5.8%, range = less than 1 to 30%, n = 52) of the mRNAs obtained from PBMCs. In contrast, the R46X mutation is present in the genomic DNA of PBMCs at very low levels. Examination of the PBMC cell-type subsets identifies monocytes and natural killer (NK) cells as primary sources of the mutant transcript, although lesser contributions also come from B and T lymphocytes. Transcript sequence analyses in leukemic cell lines derived from monocyte, NK, T and B cells indicate that the mutational mechanism targeting SDHB is operational in T-cell acute leukemia. Accordingly, substantial levels (more than 3%) of the mutant SDHB transcripts are detected in five of 20 primary childhood T-cell acute lymphoblastic leukemia (T-ALL) bone marrow samples, but in none of 20 B-ALL samples. In addition, distinct heterozygous SDHB missense DNA mutations are identified in Jurkat and TALL-104 cell lines which are derived from T-ALLs. CONCLUSIONS: The identification of a recurrent, inactivating stop-codon mutation in the SDHB gene in normal blood cells suggests that SDHB is targeted by a cytidine deaminase enzyme. The SDHB mutations in normal PBMCs and leukemic T cells might play a role in cellular pre-adaptation to hypoxia.

[Oxidative stress and oxygen status in ischemic stroke].

A dynamic assessment of oxygen status of the arterial blood, activity of antioxidant system enzymes (AOS), succinatedehydrogenase (SDG), mitochondrial alpha-glycero-phosphate-dehydrogenase (alpha-GPDH) and alkaline phosphatase (AP) as well as concentrations of reduced glutathione (GSH) and secondary products of lipid peroxidation reacting with thiobarbituric acid (PLPRTA) has been carried out in patients at the acute stage of ischemic stroke of hemispheric location. Relative hyperoxia as a result of the hyperventilation syndrome was mostly pronounced on day 1 and 3. At the same time, a reduced activity of AOS system and an increase of PLPRTA concentration have been observed from the 1st day after stroke. There were also a decrease of the SDG activity and a marked (2,8 fold) increase of the alpha-GPDH activity as compared to the controls. A decrease of the AP leukocyte activity in the peripheral blood to day 7 after stroke makes possible a prognosis of good functional rehabilitation to the 21st day of the disease. Therefore, the results of the study suggest that the development of oxidative stress in patients with ischemic stroke is caused by tprimary disruption of bioenergetic processes during the reduction of AOS activity.

[Peculiarity of cell energy metabolism in newborns with hypoxic-ischemic encephalopathy caused by asphyxia].

The authors have studied changes of activity of succinate dehydrogenase (SD) of peripheral blood lymphocytes of newborn with hypoxic-ischemic encephalopathy at early neonatal period and against cerebrokurin medicine administration. Newborn children with hypoxic-ischemic encephalopathy due to severe asphyxia have significant disturbancies of cyto-energy metabolism which is proved through decrease in activity index of SD and decrease in quantity of the cells with moderate and high activity. Lymphocytes of newborns with severe asphyxia were caracterized on six days by absence of the cells with moderate and high activity. Newborns with severe asphyxia who had been prescribed cerebrokurin had on their six days considerable increase in lymphocytes with moderate and high activity.