Increased Trimethylamine N-Oxide Is Not Associated with Oxidative Stress Markers in Healthy Aged Women.

Increased plasma trimethylamine N-oxide (TMAO) levels have been associated with cardiovascular diseases (CVD). L-carnitine induces TMAO elevation in human blood, and thus, it has been suggested as developing atherosclerosis. The aim of this study was to determine the relation between selected markers of oxidative stress and plasma TMAO concentration induced by L-carnitine supplementation for 24 weeks in healthy aged women. Twenty aged women were supplemented during 24 weeks with either 1500 mg L-carnitine-L-tartrate (n = 11) or isonitrogenous placebo (n = 9) per day. Fasting blood samples were taken from antecubital vein. L-carnitine supplementation induced an increase in TMAO, but not in γ-butyrobetaine (GBB). Moreover, there were no significant changes in serum ox-LDL, myeloperoxidase, protein carbonyls, homocysteine, and uric acid concentrations due to supplementation. Significant reduction in white blood cell counts has been observed following 24-week supplementation, but not attributable to L-carnitine. Our results in healthy aged women indicated no relation between TMAO and any determined marker of oxidative stress over the period of 24 weeks. At the same time, plasma GBB levels were not affected by L-carnitine supplementation. Further clinical studies of plasma GBB level as a prognostic marker are needed.

Acute Sprint Interval Exercise Increases Both Cognitive Functions and Peripheral Neurotrophic Factors in Humans: The Possible Involvement of Lactate.

There is increasing attention to sprint interval exercise (SIE) training as a time-efficient exercise regime. Recent studies, including our own (Kujach et al., 2018), have shown that acute high-intensity intermittent exercise can improve cognitive function; however, the neurobiological mechanisms underlying the effect still remain unknown. We thus examined the effects of acute SIE on cognitive function by monitoring the peripheral levels of growth and neurotrophic factors as well as blood lactate (LA) as potential mechanisms. Thirty-six young males participated in the current study and were divided into two groups: SIE (n = 20; mean age: 21.0 ± 0.9 years) and resting control (CTR) (n = 16; mean age: 21.7 ± 1.3 years). The SIE session consisted of 5 min of warm-up exercise and six sets of 30 s of all-out cycling exercise followed by 4.5 min of rest on a cycling-ergometer. Blood samples to evaluate the changes of serum concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and blood LA were obtained at three time points: before, immediately after, and 60 min after each session. A Stroop task (ST) and trail making test (TMT) parts A and B were used to assess cognitive functions. Acute SIE shortened response times for both the ST and TMT A and B. Meanwhile, the peripheral levels of BDNF, IGF-1, and VEGF were significantly increased after an acute bout of SIE compared to those in CTR. In response to acute SIE, blood LA levels significantly increased and correlated with increased levels of BDNF, IGF-1, and VEGF. Furthermore, cognitive function and BDNF are found to be correlated. The current results suggest that SIE could have beneficial effects on cognitive functions with increased neuroprotective factors along with peripheral LA concentration in humans.

Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver.

The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise.

The effect of ethyl pyruvate supplementation on rat fatty liver induced by a high-fat diet.

Continuous positive energy imbalance leads to obesity, which increases the risk of developing non-alcoholic fatty liver disease. The hepatoprotective effect of ethyl pyruvate has been revealed in several studies. Therefore, we examined the effect of ethyl pyruvate supplementation on liver cell damage, metabolism, membrane fluidity, and oxidative stress markers in rats fed a high-fat diet. After 6-wk feeding of a control or high-fat diet, Wistar rats were divided into 4 groups: control diet, control diet and ethyl pyruvate, high-fat diet, and high-fat diet and ethyl pyruvate. Ethyl pyruvate was administered as a 0.3% solution in drinking water, for the following 6 wk. Ethyl pyruvate intake attenuated the increase in activities of plasma transaminases and liver TNF-α. However, the supplementation was without effect in the lipid profiles, membrane fluidity or oxidative metabolism in liver induced by the high-fat diet. Our data confirm the potency of ethyl pyruvate against cell liver damage. Nevertheless, prolonged intake did not affect the development of a fatty liver.

Exercise-induced heart mitochondrial cholesterol depletion influences the inhibition of mitochondrial swelling.

The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown. Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling. Male Wistar rats were divided into a sedentary control group and an exercise group. The rats exercised for 3 h, burdened with an additional 3% of their body weight. Their hearts were removed immediately after completing the exercise. The left ventricle was divided and used for experiments. Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria. To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-ß-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group. Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction. Similar results were achieved in control mitochondria treated with 2% methyl-ß-cyclodextrin. All of the mitochondrial bioenergetics parameters were similar between the groups. Therefore, the disruption of raft-like microdomains appears to be an adaptive change in the rat heart following exercise.

Five-day whole-body cryostimulation, blood inflammatory markers, and performance in high-ranking professional tennis players.

CONTEXT: Tournament season can provoke overreaching syndrome in professional tennis players, which may lead to deteriorated performance. Thus, appropriate recovery methods are crucial for athletes in order to sustain high-level performance and avoid injuries. We hypothesized that whole-body cryostimulation could be applied to support the recovery process. OBJECTIVE: To assess the effects of 5 days of whole-body cryostimulation combined with moderate-intensity training on immunologic, hormonal, and hematologic responses; resting metabolic rate; and tennis performance in a posttournament season. DESIGN: Controlled laboratory study. SETTING: National Olympic Sport Centre. PATIENTS OR OTHER PARTICIPANTS: Twelve high-ranking professional tennis players. INTERVENTION(S): Participants followed a moderate-intensity training program. A subgroup was treated with the 5-day whole-body cryostimulation (-120°C) applied twice a day. The control subgroup participated in the training only. Main Outcome Measure(s): Pretreatment and posttreatment blood samples were collected and analyzed for tumor necrosis factor α, interleukin 6, testosterone, cortisol, and creatine kinase. Resting metabolic rate and performance of a tennis drill were also assessed. RESULTS: Proinflammatory cytokine (tumor necrosis factor α) decreased and pleiotropic cytokine (interleukin 6) and cortisol increased in the group exposed to cryostimulation. In the same group, greater stroke effectiveness during the tennis drill and faster recovery were observed. Neither the training program nor cryostimulation affected resting metabolic rate. CONCLUSIONS: Professional tennis players experienced an intensified inflammatory response after the completed tournament season, which may lead to overreaching. Applying whole-body cryostimulation in conjunction with moderate-intensity training was more effective for the recovery process than the training itself. The 5-day exposure to cryostimulation twice a day ameliorated the cytokine profile, resulting in a decrease in tumor necrosis factor α and an increase in interleukin 6.

Higher hypochlorous acid scavenging activity of ethyl pyruvate compared to its sodium salt.

Although a number of studies have focused on the higher ethyl pyruvate antioxidative activity than its sodium salt under various stress conditions, and the greater protective properties of the ester form have been suggested as the effect of better cell membrane penetration, the molecular mechanism has remained unclear. The aim of the present study was therefore to compare the antioxidative activities of sodium and ethyl pyruvate under in vitro conditions by using a liver homogenate as the model for cell membrane transport deletion. The potential effect of ethanol was also evaluated, and hypochlorous acid was used as an oxidant. Our data indicate the concentration-dependent scavenging potency of both sodium and ethyl pyruvate, with the ester having higher activity. This effect was not related to the presence of ethanol. Better protection of the liver homogenate by ethyl pyruvate was also apparent, despite the fact that cell membrane transport was omitted.

The effect of three days of judo training sessions on the inflammatory response and oxidative stress markers.

The main purpose of this study was to investigate how extreme physical strain influences cytokine response and oxidative stress markers by examining professional judo athletes during a typical 3-day judo training session (randori combat training). Creatine kinase (CK) activity, a marker of muscle damage, was considerably elevated immediately after randori training. Pro- (IL-1ß and TNF-α) and anti-inflammatory (IL-6 and IL-10) cytokines were also increased. The strongest effect was seen in IL-1ß concentration, which correlated with CK activity (r = 0.49, P < 0.05). All the observed cytokines returned to baseline (IL-1ß) or even dropped below initial levels (TNF-α, IL-6 and IL-10) 12 h after completing the training. Lipid peroxides (LPO), a marker of reactive oxygen species, also decreased below their initial values. LPO levels correlated directly with IL-1ß, TNF-α, IL-6 and IL-10. This study is the first to evaluate the effect of a 3-day judo training session on muscle damage by evaluating the release of pro- and anti-inflammatory cytokines and markers of oxidative stress. It is also the first to demonstrate significant changes in the blood cytokine profile that correlate with lipid peroxide levels and muscle damage.

Methyl-beta-cyclodextrin induces mitochondrial cholesterol depletion and alters the mitochondrial structure and bioenergetics.

There is growing evidence of mitochondrial membrane raft-like microdomains that are involved in the apoptotic pathway. The aim of this study was to investigate the effect of methyl-beta-cyclodextrin (MßCD), being a well-known lipid microdomain disrupting agent and cholesterol chelator, on the structure and bioenergetics of rat liver mitochondria (RLM). We observed that MßCD decreases the function of RLM, induces changes in the mitochondrial configuration state and decreases the calcium chloride-induced swelling. These data suggest that disruption of mitochondrial raft-like microdomains by cholesterol efflux on one hand impairs mitochondrial bioenergetics, but on the other hand it protects the mitochondria from swelling.

Antioxidant activity of NADH and its analogue--an in vitro study.

The antioxidant activities of NADH and of its analogue, 1,4-dihydro-2,6-dimethyl-3,5-dicarbethoxy-pyridine (PyH(2)), were evaluated in vitro. NADH was found to be oxidized by the peroxyl radical derived from 2,2-azobis-(2-amidinopropane) dihydrochloride (AAPH) decomposition, in a pH-dependent manner. Both NADH and PyH(2) inhibited the peroxidation of egg yolk lecithin (EYL) liposomes, although PyH(2) was more effective than NADH when 2,2'-azobis-4-methoxy-2,4-dimethyl-valeronitrile (methoxy-AMVN) was employed to induce EYL liposome peroxidation. The antioxidant activities of NADH and PyH(2) were also evaluated by measuring their influences on 1,3-diphenylisobenzofuran (DPBF) fluorescence decay in the presence of peroxyl radicals. NADH and PyH(2) were much more effective at inhibiting DPBF quenching in Triton X-100 micelles than in liposomes. These results indicate that NADH can inhibit lipid peroxidation despite being hydrophilic. Nevertheless, membrane penetration is an important factor and limits its antioxidant activity.