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Schematic representing the reactive oxygen species and reactive nitrogen species influence in different conditions. The red arrow represents the causes of ROS and RNS generation, the green arrow represents the cause of elimination.
Source publication
The contractile activity, high oxygen consumption and metabolic rate of skeletal muscle cause it to continuously produce moderate levels of oxidant species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Under normal physiological conditions, there is a dynamic balance between the production and elimination of ROS/RNS. H...
Context in source publication
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Skeletal muscle mass responds rapidly to growth stimuli, precipitating hypertrophies (increased protein synthesis) and hyperplasia (activation of the myogenic program). For ages, muscle degeneration has been attributed to changes in the intracellular myo ber pathways. ese pathways are tightly regulated by hormones and lymphokines that ultimately pa...
Citations
... A novel observation was that even in normal WT muscles, the amount of oxidised albumin is considerably (approximately 4-fold) higher than for plasma, suggesting that the movement of albumin through tissue is a significant source of oxidation. This may be particularly true for muscle, which produces significant oxidants due to its contractile activity and high oxygen consumption [52]. ...
Redox modifications to the plasma protein albumin have the potential to be used as biomarkers of disease progression and treatment efficacy in pathologies associated with inflammation and oxidative stress. One such pathology is Duchenne muscular dystrophy (DMD), a fatal childhood disease characterised by severe muscle wasting. We have previously shown in the mdx mouse model of DMD that plasma albumin thiol oxidation is increased; therefore, the first aim of this paper was to establish that albumin thiol oxidation in plasma reflects levels within mdx muscle tissue. We therefore developed a method to measure tissue albumin thiol oxidation. We show that albumin thiol oxidation was increased in both mdx muscle and plasma, with levels correlated with measures of dystropathology. In dystrophic muscle, albumin content was associated with areas of myonecrosis. The second aim was to test the ability of plasma thiol oxidation to track acute changes in dystropathology: we therefore subjected mdx mice to a single treadmill exercise session (known to increase myonecrosis) and took serial blood samples. This acute exercise caused a transient increase in total plasma albumin oxidation and measures of dystropathology. Together, these data support the use of plasma albumin thiol oxidation as a biomarker to track active myonecrosis in DMD.
... The accumulation of lipid peroxides can cause damage to the cellular membranes and regulate various physiological processes, such as inflammation, cell death and angiogenesis (Ghirmai et al. 2022). Moreover, oxidative stress reduces energy availability, altering the metabolism of carbohydrates and impairing the function of muscles and the cardiovascular system by decreasing swimming ability and raising susceptibility to disease and predation (Lawrence et al. 2019;Palstra et al. 2018;Jannas-Vela et al. 2020;Lian et al. 2022). Changes in energy metabolism can be detected via lactate levels, a byproduct that accumulates in fish's blood during high-intensity swimming (Johnston and Goldspink 1973;Yu et al. 2022). ...
Understanding the swimming ability of different fish species is essential for assessing their ecological niche, behaviour and overall fitness. Changes in swimming ability can relate to the overall health of aquatic ecosystems, as it can be affected by water quality, temperature or habitat quality changes. Our study investigated the effects of stress on swimming performance in wild vairone (Telestes muticellus) in an experimental flume. The obtained data was analysed using k-means clustering to identify stress response patterns. Our findings demonstrate that k-means clustering effectively identified distinct subgroups of fish with similar stress responses in groups with physiological stress responses with high individual variability. We found that short-term exposure to a stress source such as high-velocity running water can increase swimming endurance in this species concerning the velocity in the setup, which was mainly seen in the cortisol and MDA levels in the muscle tissue of the fish. The velocity of the water showed limitations on swimming ability tests and highlighted that fish have a specific range of swimming speeds that they can sustain.
... Oxidative stress is associated with the impaired skeletal muscle function and locomotor activity observed in the CCl 4 -treated animals Lian et al., 2022). Artemisinic compounds, especially ARTHD, alleviated the weight-lifting score and time spent on the inverted screen compared to the disease control. ...
Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p<0.05) attenuated the memory deficit, anxiety, and depressive-like behavior. Moreover, histopathological, hematological, serological, and endogenous antioxidant profiles indicated substantial AIP of ACs. Findings of comet assay further bolstered the compelling evidence as DNA damage was significantly (p<0.05) curbed down after ACs (100 mg/kg) treatment. All these outcomes implied that ACs exhibited AIP in a dose-dependent manner with maximal AIP imparted by artemisinin (100 mg/kg). This pre-clinical investigation avers the tremendous AIP of ACs targeting key molecular pathways. The current study divulges artemisinin as the most potent antiinflammatory agent among the tested compounds.
... The different effect exerted by PXS-5131 on reactive oxygen species (ROS) levels in the diaphragm and tibialis anterior was somewhat unexpected; such findings could be due to different levels of ROS production and/or to different roles played by MAO-B and SSAO in the two muscles. In this regard it is worth noting that both activity levels and fiber types are known to affect the levels of oxidative stress [41], as it is also suggested by the fiber type-specific effects on muscle contractility in wild-type and dystrophic muscles [42]. A similar muscle fiber-specific response was seen in selenoprotein N KO mice, in which an increased oxida-tive stress in the sarcoplasmic reticulum specifically affected the diaphragm, but not the hindlimb muscles [43,44]. ...
Duchenne muscular dystrophy (DMD) is one of the most frequent and severe childhood muscle diseases. Its pathophysiology is multifaceted and still incompletely understood, but we and others have previously shown that oxidative stress plays an important role. In particular, we have demonstrated that inhibition of mitochondrial monoamine oxidases could improve some functional and biohumoral markers of the pathology. In the present study we report the use of dystrophic mdx mice to evaluate the efficacy of a dual monoamine oxidase B (MAO-B)/semicarbazide-sensitive amine oxidase (SSAO) inhibitor, PXS-5131, in reducing inflammation and fibrosis and improving muscle function. We found that a one-month treatment starting at three months of age was able to decrease reactive oxygen species (ROS) production, fibrosis, and inflammatory infiltrate in the tibialis anterior (TA) and diaphragm muscles. Importantly, we also observed a marked improvement in the capacity of the gastrocnemius muscle to maintain its force when challenged with eccentric contractions. Upon performing a bulk RNA-seq analysis, PXS-5131 treatment affected the expression of genes involved in inflammatory processes and tissue remodeling. We also studied the effect of prolonged treatment in older dystrophic mice, and found that a three-month administration of PXS-5131 was able to greatly reduce the progression of fibrosis not only in the diaphragm but also in the heart. Taken together, these results suggest that PXS-5131 is an effective inhibitor of fibrosis and inflammation in dystrophic muscles, a finding that could open a new therapeutic avenue for DMD patients.
... The condition of high oxidative activity and high IMCLs content could be harmful for the muscle cells. Moreover, the increased mitochondrial respiration could lead to an increase in reactive oxygen species over the physiological levels [44]. A high IMCLs content could compromise excitation-contraction coupling and contractile function of the skeletal muscle [45,46]. ...
In the context of the increasing number of obese individuals, a major problem is represented by obesity and malnutrition in children. This condition is mainly ascribable to unbalanced diets characterized by high intakes of fat and sugar. Childhood obesity and malnutrition are not only associated with concurrent pathologies but potentially compromise adult life. Considering the strict correlation among systemic metabolism, obesity, and skeletal muscle health, we wanted to study the impact of juvenile malnutrition on the adult skeletal muscle. To this aim, 3-week-old C56BL/6 female and male mice were fed for 20 weeks on a high-fat. high-sugar diet, and their muscles were subjected to a histological evaluation. MyHCs expression, glycogen content, intramyocellular lipids, mitochondrial activity, and capillary density were analyzed on serial sections to obtain the metabolic profile. Our observations indicate that a high-fat, high-sugar diet alters the metabolic profile of skeletal muscles in a sex-dependent way and induces the increase in type II fibers, mitochondrial activity, and lipid content in males, while reducing the capillary density in females. These data highlight the sex-dependent response to nutrition, calling for the development of specific strategies and for a systematic inclusion of female subjects in basic and applied research in this field.
... As a consequence of EIMD, inflammatory cells such as neutrophils and macrophages are recruited to the site of damage to remove debris and initiate a number of signalling cascades within the muscle myofiber and extracellular matrix to stimulate repair and remodelling (Bernard et al. 2022;Peake et al. 2017;Tidball 2005;Toumi et al. 2006). Inflammatory cells are also a source of ROS, with ROS being evident following EIMD and subsequent repair of skeletal muscle (Kozakowska et al. 2015;Lian et al. 2022;Powers & Schrager 2022). The increase in ROS following EIMD has been proposed to cause secondary muscle damage to uninjured muscle fibres via direct oxidative damage to biomolecules or indirect induction of inflammatory cytokines (Kawamura & Muraoka 2018;Paschalis et al. 2013;Powers et al. 2011). ...
Purpose
Exercise-induced muscle damage (EIMD) results in the generation of reactive oxygen species (ROS), but little is known about the temporal profile of change in ROS post-EIMD and how ROS levels relate to the onset of and recovery from EIMD. Our primary aim was to examine the effect of EIMD on the pattern of change in the blood level of thiol-oxidised albumin, a marker of oxidative stress.
Methods
Seven male participants were subjected on separate days to eccentric muscle contraction to cause EIMD or a no-exercise condition. After each session, the participants collected daily dried blood spots to measure thiol-oxidised albumin and returned to the laboratory every 2 days for the assessment of indirect markers of EIMD, namely maximal voluntary contraction (MVC), delayed onset muscle soreness (DOMS), creatine kinase (CK), and myoglobin.
Results
Eccentric exercise resulted in a significant decrease in MVC and increase in DOMS, CK, myoglobin, and thiol-oxidised albumin with the latter reaching above baseline level within 24–48 h post-exercise. All the markers of EIMD returned to baseline level within 6 days post-exercise, but not the level of thiol-oxidised albumin which remained elevated for 10 days after exercise. There was a moderate correlation between changes in thiol-oxidised albumin and DOMS, but no significant relationship between any other markers of muscle damage.
Conclusion
The levels of thiol-oxidised albumin increase in response to EIMD and remain elevated for several days post-exercise. The temporal pattern of change in the level of thiol-oxidised albumin suggests that this may be a useful biomarker of muscle repair post-EIMD.
... The SOD enzyme assumes a crucial role in safeguarding cells against oxidative stress by eliminating ROS and curbing their accumulation [50]. Excessive ROS production in myotubes can suppress Akt/mTOR signaling and muscle protein synthesis, leading to accelerated protein degradation [51]. Furthermore, heightened ROS generation stands as a characteristic feature of skeletal muscle atrophy induced by DEX or fasting [52,53]. ...
Lycii Radicis Cortex (LRC) is a traditional medicine in East Asia with various beneficial effects, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and anti-depressant properties. However, its potential effects on skeletal muscle atrophy have not been studied. In this study, the protective effects of LRC extract (LRCE) on dexamethasone (DEX)-induced muscle atrophy were investigated in C2C12 myotubes and mice. We evaluated the effect of LRCE on improving muscle atrophy using a variety of methods, including immunofluorescence staining, quantitative polymerase chain reaction (qPCR), Western blot, measurements of oxidative stress, apoptosis, ATP levels, and muscle tissue analysis. The results showed that LRCE improved myotube diameter, fusion index, superoxide dismutase (SOD) activity, mitochondrial content, ATP levels, expression of myogenin and myosin heavy chain (MHC), and reduced reactive oxygen species (ROS) production in dexamethasone-induced C2C12 myotubes. LRCE also enhanced protein synthesis and reduced protein degradation in the myotubes. In mice treated with DEX, LRCE restored calf thickness, decreased mRNA levels of muscle-specific RING finger protein 1 (MuRF1) and atrogin-1, and increased insulin-like growth factor 1 (IGF-1) mRNA level. Moreover, LRCE also repaired gastrocnemius muscle atrophy caused by DEX. Although human studies are not available, various preclinical studies have identified potential protective effects of LRCE against muscle atrophy, suggesting that it could be utilized in the prevention and treatment of muscle atrophy.
... Skeletal muscle is one of the human body's most active and flexible tissues. Muscle mass loss, mostly determined by an unbalance between protein synthesis and breakdown, is influenced by several factors such as increased levels of oxidative stress, chronic inflammation, and alteration of hormone levels, which often occur during aging and in several pathological disorders [173][174][175]. In these conditions, not only the regenerative process is compromised but also NMJ degeneration may occur, seemingly linked to the failure of muscle reinnervation [132]. ...
Skeletal muscle is characterized by a remarkable capacity to rearrange after physiological changes and efficiently regenerate. However, during aging, extensive injury, or pathological conditions, the complete regenerative program is severely affected, with a progressive loss of muscle mass and function, a condition known as sarcopenia. The compromised tissue repair program is attributable to the gradual depletion of stem cells and to altered regulatory signals. Defective muscle regeneration can severely affect re-innervation by motor axons, and neuromuscular junctions (NMJs) development, ultimately leading to skeletal muscle atrophy. Defects in NMJ formation and maintenance occur physiologically during aging and are responsible for the pathogenesis of several neuromuscular disorders. However, it is still largely unknown how neuromuscular connections are restored on regenerating fibers. It has been suggested that attractive and repelling signals used for axon guidance could be implicated in this process; in particular, guidance molecules called semaphorins play a key role. Semaphorins are a wide family of extracellular regulatory signals with a multifaceted role in cell-cell communication. Originally discovered as axon guidance factors, they have been implicated in cancer progression, embryonal organogenesis, skeletal muscle innervation, and other physiological and developmental functions in different tissues. In particular, in skeletal muscle, specific semaphorin molecules are involved in the restoration and remodeling of the nerve-muscle connections, thus emphasizing their plausible role to ensure the success of muscle regeneration. This review article aims to discuss the impact of aging on skeletal muscle regeneration and NMJs remodeling and will highlight the most recent insights about the role of semaphorins in this context.
... Skeletal muscles are the biggest oxygen consumers; therefore, they release large quantities of H-FRs that, when accumulated, exert negative impacts on muscular function via some examined cellular pathways [76]. First, due to the restricted function of intrinsic and extrinsic antioxidants, the H-FRs accumulate with aging in the skeletal muscles, leading to numerous harmful cellular processes like carbonylation (e.g., Z-4-hydroxy-2-nonenal), nitrosylation (e.g., nitrotyrosine), and glycation (e.g., AGEs) [77]. Second, H-FRs contribute to aging-related muscular weakness by up-regulating proteolysis and down-regulating proteogenesis in the skeletal muscles, resulting in low muscular mass [78]. ...
The production of harmful free radicals (H-FRs), especially those with oxygen or nitrogen atoms, depends on both internal and environmental causes. The negative effects of H-FRs are greatly alleviated by antioxidant protection. The harmful impact of oxidative stress, or OS, is brought on by a disparity between the defense mechanisms of the body and the creation of H-FRs. Aging is characterized by a slow decline in tissue and organ competence. Age-mediated pathologies start as an aberrant accumulation of H-FRs, which inhibit cells’ capacity to divide, repair, and operate, based on the OS theorem of aging. The natural outcome of this situation is apoptosis. These conditions may include skeletal muscle dysfunction, cancer, cardiovascular, chronic hepatitis, chronic renal, and chronic pulmonary disorders. Given the substantial role that OS plays in the progression of many of these illnesses, antioxidant-based therapy may have a favorable impact on how these diseases progress. To ascertain the true efficacy of this therapy strategy, more research is necessary. The aim of this study is to provide an overview of the literature on this challenging issue that is attracting interest.
... The concept of the damaging effects of exercise-induced oxidative stress during acute intense or prolonged exercise has been reported extensively in the literature over the years [1][2][3][4]. In terms of exercise-induced oxidative stress, there is accumulating evidence showing that there is an appropriate concentration of reactive oxygen species (ROS) with which positive physiological adaptations may occur; however, there is also evidence that ROS production can cause micromolecular structural damage or inflammation [5][6][7]. It has also been shown that specific training adaptations may occur as a result of chronic exercise, which promotes antioxidant activity [8,9]. ...
High-intensity interval exercise (HIIE) is a type of structured physical training characterized by repeated bouts of high-intensity exercise interspersed with recovery periods. Although HIIE was found to improve physical performance in a relatively short period of time, there is emerging evidence suggesting that acute HIIE may induce oxidative stress. The purpose, therefore, of the present study was to examine the effect of intermittency and/or acceleration during HIIE on oxidative stress in male participants. Nine healthy males [(age: 21.0 ± 3.0 years; height: 180.0 ± 4.0 cm; body mass: 79.4 ± 7.9 kg; maximal oxygen uptake (V˙O2max) 52.0 ± 6.0 mL·kg−1·min−1)] were recruited to perform six distinct exercise protocols of various intermittency (high, medium, and low) and acceleration (high, medium, and low) while a control session was also included. Blood samples were obtained to determine oxidative stress indices (lipid hydroperoxides, superoxide dismutase, and total glutathione) at rest, 1 h, 2 h, and 24 h following exercise on a non-motorized treadmill. The intra-individual variability of participants was observed in lipid hydroperoxides at baseline, ranging from 1.80 to 20.69 μmol·L−1. No significant differences among the six different exercise protocols in any of the oxidative stress indices evaluated were observed (p > 0.05). These results suggest that the influence of various intermittency levels and acceleration patterns upon exercise-induced oxidative stress is negligible.
