Long-term iron supplementation combined with vitamin B6 enhances maximal oxygen uptake and promotes skeletal muscle-specific mitochondrial biogenesis in rats.

Introduction: Iron is an essential micronutrient that plays a crucial role in various biological processes. Previous studies have shown that iron supplementation is related to exercise performance and endurance capacity improvements. However, the underlying mechanisms responsible for these effects are not well understood. Recent studies have suggested the beneficial impact of iron supplementation on mitochondrial function and its ability to rescue mitochondrial function under adverse stress in vitro and rodents. Based on current knowledge, our study aimed to investigate whether the changes in exercise performance resulting from iron supplementation are associated with its effect on mitochondrial function. Methods: In this study, we orally administered an iron-based supplement to rats for 30 consecutive days at a dosage of 0.66 mg iron/kg body weight and vitamin B6 at a dosage of 0.46 mg/kg. Results: Our findings reveal that long-term iron supplementation, in combination with vitamin B6, led to less body weight gained and increased VO2 max in rats. Besides, the treatment substantially increased Complex I- and Complex II-driven ATP production in intact mitochondria isolated from gastrocnemius and cerebellum. However, the treatment did not change basal and succinate-induced ROS production in mitochondria from the cerebellum and skeletal muscle. Furthermore, the iron intervention significantly upregulated several skeletal muscle mitochondrial biogenesis and metabolism-related biomarkers, including PGC-1α, SIRT1, NRF-2, SDHA, HSL, MTOR, and LON-P. However, it did not affect the muscular protein expression of SIRT3, FNDC5, LDH, FIS1, MFN1, eNOS, and nNOS. Interestingly, the iron intervention did not exert similar effects on the hippocampus of rats. Discussion: In conclusion, our study demonstrates that long-term iron supplementation, in combination with vitamin B6, increases VO2 max, possibly through its positive role in regulating skeletal muscle-specific mitochondrial biogenesis and energy production in rats.

Single Dose Administration of Taheebo Polyphenol Enhances Endurance Capacity in Mice.

Endurance capacity is important for maintenance of quality of life as well as performance of endurance athletes. In order to improve endurance, intake of nutritional supplements as well as exercise training is also important. Indeed, polyphenolic extracts from plants are known to improve endurance capacity via increase of fatty acid utilization, mitochondrial biogenesis or inhibition of oxidative stress. Taheebo, the extract obtained from inner bark of Tabebuia avellanedae has been reported to have beneficial effects for treatment of inflammation, oxidative stress and obesity. Here, we investigated the effects and mechanisms of polyphenol fraction of taheebo (taheebo polyphenol; TP) on endurance capacity of mice. Single dose administration of TP significantly increased running time until exhaustion. Acute TP administration increased blood glucose and muscle glycogen levels (p < 0.05) through alteration on expression level of genes involved with glycogen metabolism and gluconeogenesis. Furthermore, TP administration decreased exercise-induced increase of protein carbonyls in skeletal muscle. These results suggest that TP administration improve endurance capacity via up-regulation of skeletal muscle glycogen levels and maintenance of blood glucose by acceleration of gluconeogenesis as well as inhibition of exercise-induced oxidative stress. Single administration of TP also increased phosphorylation of AMP-activated protein kinase (AMPK) and gene expression level of sirtuin 1 (SIRT1) but did not change the marker of mitochondrial biogenesis.

Pollen-induced oxidative DNA damage response regulates miRNAs controlling allergic inflammation.

A mucosal oxidative burst is a hallmark response to pollen exposure that promotes allergic inflammatory responses. Reactive species constituents of oxidative stress signal via the modification of cellular molecules including nucleic acids. One of the most abundant forms of oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase 1 (OGG1). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known. Here, we postulate that the OGG1 signaling pathway differentially altered the levels of small regulatory RNAs and increased the expression of T helper 2 (Th2) cytokines in ragweed pollen extract (RWPE)-challenged lungs. To determine this, the lungs of sensitized mice expressing or lacking OGG1 were challenged with RWPE and/or with OGG1's excision product 8-oxoG. The responses in lungs were assessed by next-generation sequencing, as well as various molecular and histological approaches. The results showed that RWPE challenge induced oxidative burst and damage to DNA and activated OGG1 signaling, resulting in the differential expression of 84 micro-RNAs (miRNAs), which then exacerbated antigen-driven allergic inflammation and histological changes in the lungs. The exogenous administration of the downregulated let-7b-p3 mimetic or inhibitors of upregulated miR-23a or miR-27a decreased eosinophil recruitment and mucus and collagen production via controlling the expression of IL-4, IL-5, and IL-13. Together, these data demonstrate the roles of OGG1 signaling in the regulation of antigen-driven allergic immune responses via differential expression of miRNAs upstream of Th2 cytokines and eosinophils.

Exogenous nicotinamide supplementation and moderate physical exercise can attenuate the aging process in skeletal muscle of rats.

Nicotinamide (NAM) could enhance the availability of NAD+ and be beneficial to cell function. However, NAM can inhibit the activities of SIRT1 and PARP. The effect of NAM supplementation on the aging process is not well known. In the present study exogenous NAM (1-0.5% in drinking water) was supplemented for 5 weeks and in the last 4 weeks moderate treadmill running was given to 5 mo and 28 mo old rats. The content of SIRT1 was not effected by NAM treatment alone. However, the activity of SIRT1, judged from the acetylated p53/p53 ratio, increased in both NAM treated age groups, suggesting beneficial effects of exogenous NAM. This was confirmed by the finding of increased PGC-1α and pCREB/CREB ratio in the gastrocnemius muscle of old but not young NAM treated animals. Our data suggest NAM administration can attenuate the aging process in skeletal muscle of rats, but NAM administration together with exercise training might be too great challenge to cope with in the old animals, since it leads to decreased levels of SIRT1.

[Correlation of the microbiota and intestinal mucosa in the pathophysiology and treatment of irritable bowel, irritable eye, and irritable mind syndrome]. / A mikroflóra és a bélnyálkahártya kölcsönhatása az irritábilis bél, irritábilis szem és irritábilis elme szindróma kórtanában és kezelésében.

Accumulating clinical evidence supports co-morbidity of irritable bowel, irritable eye and irritable mind symptoms. Furthermore, perturbation of the microbiota-host symbiosis (dysbiosis) is considered a common pathogenic mechanism connecting gastrointestinal, ocular and neuropsychiatric symptoms. Consequently, maintaining or restoring microbiota-host symbiosis represents a new approach to treat these symptoms or to prevent their relapses. Current treatment approach assigned a primary role to live probiotics alone or in combination with prebiotics to enhance colonization of beneficial bacteria and to strengthen the symbiosis. However, several papers showed major benefits of heat-killed probiotics as compared to their live counterparts on both intestinal and systemic symptoms. Recently, in addition to killing probiotics, in a proof of concept study lysates (fragments) of probiotics in combination with vitamins A, B, D and omega 3 fatty acids were successfully tested. These findings suggested a conceptual change in the approach addressed to both the microbiota and host as targets for intervention.

Influence of pulsing electromagnetic field therapy on resting blood pressure in aging adults.

This double-blind study tested the effects of pulsating electromagnetic field (PEMF) therapy sessions on the changes in peripheral cardiovascular function in a group of aging adults after 12 weeks of treatment. Each therapy session involved 15 min of exposure to low-frequency PEMF with asymmetrical waveforms emitted by the Impulser™ Pro mattress. The treatment was provided 5 days per week for a total of 60 sessions. Resting blood pressure and arterial stiffness index were determined for peripheral cardiovascular function. Fifty-four older men and women (mean age 59.8 ± 3.5 yrs) completed the entire protocol involving either the PEMF or a sham treatment. The results include statistically significant reductions in systolic and pulse blood pressure, while no significant difference in diastolic pressure or the index of arterial stiffness was observed. These findings suggest that the PEMF treatment might be linked to improvements in peripheral resistance or circulation.

The effects of cocoa supplementation, caloric restriction, and regular exercise, on oxidative stress markers of brain and memory in the rat model.

The effects of treadmill running (8 weeks, 5 times/week, 1h/day at 27 m/min), caloric restriction, and cocoa supplementation on brain function and oxidative stress markers were tested. The Morris maze test was used to appraise rat memory. Regular exercise significantly improved spatial learning performance. The level of oxidative stress was measured by the concentration of carbonylated proteins. The free radical concentration increased in brain of the training groups but not the controls. The content of reactive carbonyl derivates did not change with exercise, suggesting that the increased production of reactive oxygen species (ROS) were well tolerated in this experimental model. Caloric restriction (CR) decreased the accumulation of free radicals in the frontal lobe. The protein content of brain-derived neutrophic factors (BDNFs) was evaluated and changes did not occur either with exercise or cocoa supplementation treatments. These data did not show significant effects of the administration of cocoa (2% w/w) on the concentration of ROS, BDNF or on spatial memory. Conversely, exercise and CR can play a role in ROS generation and brain function.

Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation.

Allergic airway inflammation is characterized by increased expression of pro-inflammatory mediators, inflammatory cell infiltration, mucus hypersecretion, and airway hyperresponsiveness, in parallel with oxidative DNA base and strand damage, whose etiological role is not understood. Our goal was to establish the role of 8-oxoguanine (8-oxoG), a common oxidatively damaged base, and its repair by 8-oxoguanine DNA glycosylase 1 (Ogg1) in allergic airway inflammatory processes. Airway inflammation was induced by intranasally administered ragweed (Ambrosia artemisiifolia) pollen grain extract (RWPE) in sensitized BALB/c mice. We utilized siRNA technology to deplete Ogg1 from airway epithelium; 8-oxoG and DNA strand break levels were quantified by Comet assays. Inflammatory cell infiltration and epithelial methaplasia were determined histologically, mucus and cytokines levels biochemically and enhanced pause was used as the main index of airway hyperresponsiveness. Decreased Ogg1 expression and thereby 8-oxoG repair in the airway epithelium conveyed a lower inflammatory response after RWPE challenge of sensitized mice, as determined by expression of Th2 cytokines, eosinophilia, epithelial methaplasia, and airway hyperresponsiveness. In contrast, 8-oxoG repair in Ogg1-proficient airway epithelium was coupled to an increase in DNA single-strand break (SSB) levels and exacerbation of allergen challenge-dependent inflammation. Decreased expression of the Nei-like glycosylases Neil1 and Neil2 that preferentially excise ring-opened purines and 5-hydroxyuracil, respectively, did not alter the above parameters of allergic immune responses to RWPE. These results show that DNA SSBs formed during Ogg1-mediated repair of 8-oxoG augment antigen-driven allergic immune responses. A transient modulation of OGG1 expression/activity in airway epithelial cells could have clinical benefits.

alpha-Lipoic acid modulates thiol antioxidant defenses and attenuates exercise-induced oxidative stress in standardbred trotters.

Several micronutrient supplementation strategies are used to cope with oxidative stress, although their benefits have recently been questioned. The aim of the present study was to examine the effects of DL-alpha-lipoic acid (LA) in response to acute exercise and during recovery in horses. Six standardbred trotters were tested on the treadmill before and after 5-week LA supplementation (25 mg/kg body weight/day). According to electron paramagnetic resonance measurements, strenuous aerobic exercise increased significantly free radical formation in the gluteus medius muscle, which was prevented by LA supplementation. The activities of thioredoxin reductase and glutathione reductase in muscle were significantly increased in LA-treated horses, but neither LA nor exercise affected muscle thioredoxin activity. LA increased the concentration of total glutathione in muscle at rest and during recovery. Treatment with LA blunted the exercise-induced increase in plasma oxygen radical absorbance capacity and decreased the post-exercise levels of lipid hydroperoxides in plasma and malondialdehyde in plasma and in muscle. These findings suggest that LA enhances thiol antioxidant defences and decreases exercise-induced oxidative stress in skeletal muscle.

The beneficial effects of nettle supplementation and exercise on brain lesion and memory in rat.

Regular swimming and phytotherapeutic supplementation are assumed to alleviate the severity of neurodegeneration leading to dementia. The effect of swimming training and that of enriched lab chow containing 1% (w/w) dried nettle (Urtica dioica) leaf on the prevention of severity of brain injury caused by N-methyl-d-aspartate (NMDA) lesion in Wistar rats were investigated. Nettle supplementation and regular swimming exercise seem to improve the adverse effect of brain injury caused by NMDA lesion assessed by passive avoidance test and open-field test. Nettle supplementation decreases the level of reactive oxygen species, measured by electron paramagnetic resonance, and the DNA-binding activity of NF-kappaB. The data reveal that nettle supplementation has an effective antioxidant role, down-regulates the inflammatory transcription factors and could also promote learning performance in the brain. Regular swimming increases the concentration of reactive species in the cerebellum and alters the activity of transcription factors toward inflammation. The additive effect of the two treatments was more profound in the down-regulation of inflammatory transcription processes in NMDA lesion.

Multivitamin-mineral supplementation prevents lipid peroxidation during "the Marathon des Sables".

OBJECTIVE: We investigated the effect of a moderate mutivitamin and mineral supplementation containing mainly vitamin C (150.0 mg.day(-1)), vitamin E (24.0 mg.day(-1)) and beta-carotene (4.8 mg.day(-1)) prior to and during an extreme running competition -the Marathon des Sables (MDS)- that consisted of six long races in the desert. METHODS: Seventeen athletes participated in our double blind, placebo-controlled study. Blood samples were collected prior to the supplementation i.e. three weeks before the competition (D-21), two days prior to the MDS (D-2), after the third race (D3) and at the end of the competition (D7). Erythrocyte antioxidant enzyme activity (glutathione peroxidase (GPx), superoxide dismutase (SOD)), erythrocyte glutathione level (GSH), plasma non-enzymatic antioxidant status (uric acid, vitamin C, alpha-tocopherol, retinol, beta-carotene), markers of plasma lipid peroxidation (thiobarbituric reactive substances (TBARS)), reactive carbonyl derivatives (RCD) and membrane damage (creatine kinase and lactate dehydrogenase activities) were measured. RESULTS: In both groups, GSH levels, uric acid levels and membrane damage significantly increased during the competition while SOD activity significantly decreased. In Supplemented group, plasma alpha-tocopherol, beta-carotene and retinol levels significantly increased after three weeks of supplementing. In contrast to Placebo group, alpha-tocopherol, vitamin C and retinol levels were significantly affected by the competition in Supplemented group. Moreover, no increase in TBARS was observed in Supplemented group during the competition, whereas TBARS significantly increased at D3 in the placebo group. CONCLUSION: The moderate multivitamin-mineral supplementation prevented the transient increase in TBARS levels during this extreme competition.

The effect of exercise and nettle supplementation on oxidative stress markers in the rat brain.

Chronic swimming training and phytotherapeutic supplementation are assumed to alleviate oxidative damage, and support cell survival in the brain. The effect of forced, chronic swimming training, and enriched lab chow containing 1% (w/w) dried nettle (Urtica dioica) leaf were investigated for oxidative stress, inflammation and neurotrophic markers in Wistar rat brains. The rats were divided into groups subjected to swimming training (6 weeks) or to nettle supplementation (8 weeks) or to a combination of these two treatments. The level of oxidative stress was measured by electron spin resonance (EPR), and by the concentration of carbonylated proteins. Nettle supplementation resulted in a decreased concentration of free radicals in both cerebellum and frontal lobe. Swimming, however, did not influence significantly the oxidative damage nor was it reflected in the carbonyl content. The protein content of nerve growth factor (NGF), and brain-derived neurotrophic factors (BDNF) was evaluated by E-Max ImmunoAssay in the cerebellum. No changes occurred either with exercise or nettle diet treatments. On the other hand, nuclear factor kappa B (NF-kappaB) binding activity to DNA increased with the combined effect of swimming training and nettle diet, while the activator protein1 (AP-1) DNA binding activity showed a more profound elevation in the nettle treated animals. The amount of c-Jun decreased by swimming training. In conclusion, the results suggest that both exercise and nettle influenced physiological brain functions. Nettle supplementation reduces the free radical concentration and increases the DNA binding of AP-1 in the brain. Nettle was found to be an effective antioxidant and possible antiapoptotic supplement promoting cell survival in the brain. Exercise, as a downregulator of c-Jun and in combined group as an upregulator of NF-kappaB, may play also a role in antiapoptotic processes, which is important after brain injury.