Moringa oleifera is a multi-purpose herbal plant with numerous health benefits. In skeletal muscle cells, Moringa oleifera leaf extract (MOLE) acts by increasing the oxidative metabolism through the ...SIRT1-PPARα pathway. SIRT1, besides being a critical energy sensor, is involved in the activation related to redox homeostasis of transcription factors such as the nuclear factor erythroid 2-related factor (Nrf2). The aim of the present study was to evaluate in vitro the capacity of MOLE to influence the redox status in C2C12 myotubes through the modulation of the total antioxidant capacity (TAC), glutathione levels, Nrf2 and its target gene heme oxygenase-1 (HO-1) expression, as well as enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and transferase (GST). Moreover, the impact of MOLE supplementation on lipid peroxidation and oxidative damage (i.e., TBARS and protein carbonyls) was evaluated. Our results highlight for the first time that MOLE increased not only Nrf2 and HO-1 protein levels in a dose-dependent manner, but also improved glutathione redox homeostasis and the enzyme activities of CAT, SOD, GPx and GST. Therefore, it is intriguing to speculate that MOLE supplementation could represent a valuable nutrition for the health of skeletal muscles.
Gender-related methodology in biomedical sciences receives considerable attention, with numerous studies highlighting biological differences between cisgender males and females. These differences ...influence the clinical symptoms of various diseases and impact therapeutic approaches. In this in vitro study, we investigate the potential role of sex-chromosome-related dimorphism on steroidogenic enzymes, androgen receptor (AR) expression, and cellular translocation in primary human skeletal muscle cells before and after exposure to testosterone. We analyzed 46XY and 46XX cells for 17β-hydroxysteroid dehydrogenase (17β-HSD), 5α-reductase (5α-R2), aromatase (Cyp-19), and AR gene expression. We also compared AR expression and intracellular translocation after increasing exposure to testosterone. At baseline, we observed higher mRNA expression for 5α-R2 and AR in 46XY cells and higher Cyp-19 mRNA expression in 46XX cells. Following testosterone exposure, we observed an increase in AR expression and translocation in 46XX cells, even at the lowest dose of 0.5 nM, while significant changes in 46XY cells were observed only from 10 nM. Our in vitro results demonstrate that the diverse sex chromosome assets reflect important differences in muscle steroidogenesis. They support the concept that chromosomal disparities between males and females, even in vitro, lead to pivotal variations in cellular physiology and response. This understanding represents a crucial starting point in gender medicine, ensuring a precise approach in clinical practice, sports, and exercise settings and facilitating the translation of in vitro data to in vivo applicability.
Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud's ...Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H
O
), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc.
The aim of the present investigation was to test the hypothesis that quercetin (Q) may prevent the strength loss and neuromuscular impairment associated with eccentric exercise-induced muscle damage ...(EEIMD). Twelve young men (26.1 ± 3.1 years) ingested either Q (1000 mg/day) or placebo (PLA) for 14 days using a randomized, double-blind, crossover study design. Participants completed a comprehensive neuromuscular (NM) evaluation before, during and after an eccentric protocol able to induce a severe muscle damage (10 sets of 10 maximal lengthening contractions). The NM evaluation comprised maximal voluntary isometric contraction (MVIC) and force⁻velocity relationship assessments with simultaneous recording of electromyographic signals (EMG) from the elbow flexor muscles. Soreness, resting arm angle, arm circumference, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) were also assessed. Q supplementation significantly increased the isometric strength recorded during MVIC compared to baseline (+4.7%,
< 0.05). Moreover, the torque and muscle fiber conduction velocity (MFCV) decay recorded during the eccentric exercise was significant lower in Q compared to PLA. Immediately after the EEIMD, isometric strength, the force⁻velocity relationship and MFCV were significantly lower when participants were given PLA rather than Q. Fourteen days of Q supplementation seems able to attenuate the severity of muscle weakness caused by eccentric-induced myofibrillar disruption and sarcolemmal action potential propagation impairment.
A central feature of the skeletal muscle is its ability to regenerate through the activation, by environmental signals, of satellite cells. Once activated, these cells proliferate as myoblasts, and ...defects in this process profoundly affect the subsequent process of regeneration. High levels of reactive oxygen species such as hydrogen peroxide (H2O2) with the consequent formation of oxidized macromolecules increase myoblasts’ cell death and strongly contribute to the loss of myoblast function. Recently, particular interest has turned towards the beneficial effects on muscle of the naturally occurring polyamine spermidine (Spd). In this work, we tested the hypothesis that Spd, upon oxidative challenge, would restore the compromised myoblasts’ viability and redox status. The effects of Spd in combination with aminoguanidine (Spd-AG), an inhibitor of bovine serum amine oxidase, on murine C2C12 myoblasts treated with a mild dose of H2O2 were evaluated by analyzing: (i) myoblast viability and recovery from wound scratch; (ii) redox status and (iii) polyamine (PAs) metabolism. The treatment of C2C12 myoblasts with Spd-AG increased cell number and accelerated scratch wound closure, while H2O2 exposure caused redox status imbalance and cell death. The combined treatment with Spd-AG showed an antioxidant effect on C2C12 myoblasts, partially restoring cellular total antioxidant capacity, reducing the oxidized glutathione (GSH/GSSG) ratio and increasing cell viability through a reduction in cell death. Moreover, Spd-AG administration counteracted the induction of polyamine catabolic genes and PA content decreased due to H2O2 challenges. In conclusion, our data suggest that Spd treatment has a protective role in skeletal muscle cells by restoring redox balance and promoting recovery from wound scratches, thus making myoblasts able to better cope with an oxidative insult.
Purpose
To examine the effect of acute quercetin (Q) ingestion on neuromuscular function, biomarkers of muscle damage, and rate of perceived exertion (RPE) in response to an acute bout of resistance ...training.
Methods
10 young men (22.1 ± 1.8 years, 24.1 ± 3.1 BMI) participated in a randomized, double-blind, crossover study. Subjects consumed Q (1 g/day) or placebo (PLA) 3 h prior to a resistance training session which consisted of 3 sets of 8 repetitions at 80% of the one repetition maximum (1RM) completed bilaterally for eight different resistance exercises. Electromyographic (EMG) signals were recorded from the knee extensor muscles during maximal isometric (MVIC) and isokinetic voluntary contractions, and during an isometric fatiguing test. Mechanical and EMG signals, biomarkers of cell damage, and RPE score were measured PRE, immediately POST, and 24 h (blood indices only) following the resistance exercise.
Results
After a single dose of Q, the torque–velocity curve of knee extensors was enhanced and after the resistance exercise, subjects showed a lower MVIC reduction (Q: 0.91 ± 6.10%, PLA: 8.66 ± 5.08%) with a greater rate of torque development (+ 10.6%,
p
< 0.005) and neuromuscular efficiency ratio (+ 28.2%,
p
< 0.005). Total volume of the resistance exercises was significantly greater in Q (1691.10 ± 376.71 kg rep) compared to PLA (1663.65 ± 378.85 kg rep) (
p
< 0.05) with a comparable RPE score. No significant differences were found in blood marker between treatments.
Conclusions
The acute ingestion of Q may enhance the neuromuscular performance during and after a resistance training session.
Skeletal muscle is a tissue that has recently been recognized for its ability to produce androgens under physiological conditions. The steroidogenesis process is known to be negatively influenced by ...reactive oxygen species (ROS) in reproductive Leydig and ovary cells, while their effect on muscle steroidogenesis is still an unexplored field. Muscle cells are continuously exposed to ROS, resulting from both their metabolic activity and the surrounding environment. Interestingly, the regulation of signaling pathways, induced by mild ROS levels, plays an important role in muscle fiber adaptation to exercise, in a process that also elicits a significant modulation in the hormonal response. The aim of the present study was to investigate whether ROS could influence steroidogenesis in skeletal muscle cells by evaluating the release of testosterone (T) and dihydrotestosterone (DHT), as well as the evaluation of the relative expression of the key steroidogenic enzymes 5α-reductase, 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and aromatase. C2C12 mouse myotubes were exposed to a non-cytotoxic concentration of hydrogen peroxide (H2O2), a condition intended to reproduce, in vitro, one of the main stimuli linked to the process of homeostasis and adaptation induced by exercise in skeletal muscle. Moreover, the influence of tadalafil (TAD), a phosphodiesterase 5 inhibitor (PDE5i) originally used to treat erectile dysfunction but often misused among athletes as a “performance-enhancing” drug, was evaluated in a single treatment or in combination with H2O2. Our data showed that a mild hydrogen peroxide exposure induced the release of DHT, but not T, and modulated the expression of the enzymes involved in steroidogenesis, while TAD treatment significantly reduced the H2O2-induced DHT release. This study adds a new piece of information about the adaptive skeletal muscle cell response to an oxidative environment, revealing that hydrogen peroxide plays an important role in activating muscle steroidogenesis.
The polyphenolic flavonoid quercetin has been shown to be a powerful antioxidant, in vitro and in murine models. However, its effect on redox status has been poorly examined in humans, particularly ...in combination with strenuous exercise. We hypothesized that quercetin supplementation would beneficially affect redox homeostasis in healthy individuals undergoing eccentric exercise. To test this hypothesis, the effects of chronic consumption of quercetin on glutathione system (reduced, oxidized, and reduced to oxidized glutathione ratio), oxidative damage thiobarbituric acid reactive substances (TBARs), antioxidant enzymatic network (catalase, glutathione peroxidase, superoxide dismutase) and resistance to lysis, were investigated in erythrocytes, a traditional model widely used to study the effects of oxidative stress as well as the protective effects of antioxidants. In a two weeks controlled, randomized, crossover, intervention trial, 14 individuals ingested 2 caps (1 g/d) of quercetin or placebo. Blood samples were collected before, after 2 weeks of supplementation and after a bout of eccentric exercise. Quercetin, reduced significantly erythrocytes lipid peroxidation levels and the susceptibility to hemolysis induced by the free radical generator AAPH, while no differences in antioxidant enzyme activities and glutathione homeostasis were found between the two groups. After a single bout of eccentric exercise, quercetin supplementation improved redox status as assessed by reduced/oxidized glutathione ratio analysis and reduced TBARs levels both in erythrocytes and plasma. In conclusion, our study provides evidences that chronic quercetin supplementation has antioxidant potential prior to and after a strenuous eccentric exercise thus making the erythrocytes capable to better cope with an oxidative insult.
MVC: isometric Maximal Voluntary Contraction; HS: Handgrip Strength; FTTST: Five Times Sit-to-Stand Test; TUG: Timed Up-and-Go test; FT: Free Thiols; SOD: total Superoxide Dismutase; MDA: ...Malondialdehyde: CAT: Catalase; GSH: reduced Glutathione; GSSG: oxidized Glutathione; GPx: Glutathione Peroxidase; TAS: Total Antioxidant Status; PC: Protein Carbonyl groups.
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•The endurance training using cycloergometer increased plasma SOD activity and handgrip strength in elderly.•This effect on strength and redox homeostasis could be linked to the Bottom-Up Rise Strength Transfer (BURST) phenomenon.
We aimed to characterize the plasma redox homeostasis as underlying physiological mechanisms of specific training on healthy elderly. 51 healthy volunteers were trained to endurance, resistance, Neuro-Muscular Electrical Stimulation for 12 weeks, 3 sessions/w, all applied to lower limbs. We assessed ex-post quadriceps’ maximal voluntary contraction, handgrip strength, five-times-sit to stand and timed up-and-go tests, oxidative damage (lipid peroxidation, protein carbonyl groups), antioxidant enzyme activities (superoxide dismutase, Catalase, Glutathione peroxidase, Glutathione homeostasis), free thiols and total antioxidant status. We found significant difference in ex-post × protocol and in post-hoc analysis specifically for plasma superoxide dismutase activity in endurance training.
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