Muscle Oxidative Stress Research Articles

Prenatal transportation stress does not impact resting skeletal muscle mitochondrial function or antioxidant activity in Brahman calves

In cattle, prenatal transportation stress has been associated with differential methylation of genes related to metabolism, but the effects of prenatal transportation stress on skeletal muscle mitochondria and oxidative stress have not been investigated. We tested the hypothesis that prenatally stressed calves would exhibit increased skeletal muscle mitochondrial function resulting in greater oxidative stress than calves from non-stressed dams. Serum and longissimus thoracis muscle samples were collected from yearling Brahman calves whose mothers were stressed by transportation at five time points during gestation [i.e., prenatally stressed (PNS); eight bulls and six heifers] and control calves (CON; four bulls and six heifers). Serum was evaluated for concentration of the stress hormone, cortisol and for a marker of muscle perturbation, creatine kinase activity. Muscle samples were analyzed for concentration of a by-product of lipid peroxidation, malondialdehyde, and activity of the antioxidants, superoxide dismutase and glutathione peroxidase. Additionally, muscle mitochondrial volume density and function were estimated by citrate synthase and cytochrome c oxidase activities, respectively. Data were analyzed using mixed linear models with sex, treatment, and the sex × treatment interaction as fixed effects. No investigated variable differed between CON and PNS calves (p ≥ 0.3). These data suggest that prenatal transportation stress does not have an impact on skeletal muscle mitochondrial metabolism or markers of stress or muscle damage in Brahman yearling calves at rest. However, previously reported negative impacts of prenatal stress on inflammatory responses suggest that PNS calves may be differentially equipped to handle an acute stressor. Future research should investigate the energetic and inflammatory implications of acute stressors in animals subjected to prenatal stress.

Salbutamol Attenuates Diabetic Skeletal Muscle Atrophy by Reducing Oxidative Stress, Myostatin/GDF-8, and Pro-Inflammatory Cytokines in Rats.

Type 2 diabetes is a metabolic disorder that leads to accelerated skeletal muscle atrophy. In this study, we aimed to evaluate the effect of salbutamol (SLB) on skeletal muscle atrophy in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were divided into four groups (n = 6): control, SLB, HFD/STZ, and HFD/STZ + SLB (6 mg/kg orally for four weeks). After the last dose of SLB, rats were assessed for muscle grip strength and muscle coordination (wire-hanging, rotarod, footprint, and actophotometer tests). Body composition was analyzed in live rats. After that, animals were sacrificed, and serum and gastrocnemius (GN) muscles were collected. Endpoints include myofibrillar protein content, muscle oxidative stress and antioxidants, serum pro-inflammatory cytokines (interleukin-1β, interleukin-2, and interleukin-6), serum muscle markers (myostatin, creatine kinase, and testosterone), histopathology, and muscle 1H NMR metabolomics. Findings showed that SLB treatment significantly improved muscle strength and muscle coordination, as well as increased lean muscle mass in diabetic rats. Increased pro-inflammatory cytokines and muscle markers (myostatin, creatine kinase) indicate muscle deterioration in diabetic rats, while SLB intervention restored the same. Also, Feret's diameter and cross-sectional area of GN muscle were increased by SLB treatment, indicating the amelioration in diabetic rat muscle. Results of muscle metabolomics exhibit that SLB treatment resulted in the restoration of perturbed metabolites, including histidine-to-tyrosine, phenylalanine-to-tyrosine, and glutamate-to-glutamine ratios and succinate, sarcosine, and 3-hydroxybutyrate (3HB) in diabetic rats. These metabolites showed a pertinent role in muscle inflammation and oxidative stress in diabetic rats. In conclusion, findings showed that salbutamol could be explored as an intervention in diabetic-associated skeletal muscle atrophy.

N-acetylcysteine alleviates oxidative stress and apoptosis and prevents skeletal muscle atrophy in type 1 diabetes mellitus through the NRF2/HO-1 pathway

AimsType 1 diabetes mellitus (T1DM) has been linked to the occurrence of skeletal muscle atrophy. Insulin monotherapy may lead to excessive blood glucose fluctuations. N-acetylcysteine (NAC), a clinically employed antioxidant, possesses cytoprotective, anti-inflammatory, and antioxidant properties. The objective of our study was to evaluate the viability of NAC as a supplementary treatment for T1DM, specifically regarding its therapeutic and preventative impacts on skeletal muscle. Main methodsHere, we used beagles as T1DM model for 120d to explore the mechanism of NRF2/HO-1-mediated skeletal muscle oxidative stress and apoptosis and the therapeutic effects of NAC. Oxidative stress and apoptosis related factors were analyzed by immunohistochemistry, immunofluorescence, western blotting, and RT-qPCR assay. Key findingsThe findings indicated that the co-administration of NAC and insulin led to a reduction in creatine kinase levels, preventing weight loss and skeletal muscle atrophy. Improvement in the reduction of muscle fiber cross-sectional area. The expression of Atrogin-1, MuRF-1 and MyoD1 was downregulated, while Myh2 and MyoG were upregulated. In addition, CAT and GSH-Px levels were increased, MDA levels were decreased, and redox was maintained at a steady state. The decreased of key factors in the NRF2/HO-1 pathway, including NRF2, HO-1, NQO1, and SOD1, while KEAP1 increased. In addition, the apoptosis key factors Caspase-3, Bax, and Bak1 were found to be downregulated, while Bcl-2, Bcl-2/Bax, and CytC were upregulated. SignificanceOur findings demonstrated that NAC and insulin mitigate oxidative stress and apoptosis in T1DM skeletal muscle and prevent skeletal muscle atrophy by activating the NRF2/HO-1 pathway.

Bacillus coagulans T4 and Lactobacillus paracasei TD3 Ameliorate Skeletal Muscle Oxidative Stress and Inflammation in High-Fat Diet-Fed C57BL/6J Mice.

This study aims to investigate the effects of Bacillus coagulans T4 and Lactobacillus paracasei TD3 probiotics on skeletal muscle inflammation and oxidative stress in C57BL/6J mice fed a high-fat diet (HFD). Probiotics B. coagulans T4, and L. paracasei TD3 were administered to male C57BL/6J mice fed with HFD. The gene expression of macrophage infiltration markers, inflammatory cytokines, and oxidative stress indicators in the muscle tissue was investigated. Treatment with B. coagulans T4 and L. paracasei TD3 reduced macrophage infiltration, accompanied by a decrease in the expression of monocyte chemoattractant protein-1 (MCP-1) and an increase in the expression of interleukin (IL)-10. On the other hand, L. paracasei TD3 decreased malondialdehyde (MDA) while B. coagulans T4 decreased carbonyl and increased catalase activity. Treatment with probiotics B. coagulans T4 and L. paracasei TD3 partially ameliorated obesity-induced skeletal muscle inflammation in HFD-fed mice.

Cordycepin inhibits myogenesis via activating the ERK1/2 MAPK signalling pathway in C2C12 cells

Cordycepin (with a molecular formula of C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, has an important regulatory effect on skeletal muscle remodelling and quality maintenance. The aim of this study was to investigate the effect of cordycepin on myoblast differentiation and explore the underlying molecular mechanisms of this effect. Our results showed that cordycepin inhibited myogenesis by downregulating myogenic differentiation (MyoD) and myogenin (MyoG), preserved undifferentiated reserve cell pools by upregulating myogenic factor 5 (Myf5) and retinoblastoma-like protein p130 (p130), and enhanced energy reserves by decreasing intracellular reactive oxygen species (ROS) and enhancing mitochondrial membrane potential, mitochondrial mass, and ATP content. The effect of cordycepin on myogenesis was associated with increased phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2). PD98059 (a specific inhibitor of p-ERK1/2) attenuated the inhibitory effect of cordycepin on C2C12 differentiation. The present study reveals that cordycepin inhibits myogenesis through ERK1/2 MAPK signalling activation accompanied by an increase in skeletal muscle energy reserves and improving skeletal muscle oxidative stress, which may have implications for its further application for the prevention and treatment of degenerative muscle diseases caused by the depletion of depleted muscle stem cells.

Recovery kinetics following eccentric exercise is volume-dependent

ABSTRACT The present study compared the effect of 75 vs 150 vs 300 intensity-matched eccentric contractions on muscle damage and performance recovery kinetics. Ten healthy males participated in a randomized, cross-over study consisted of 4 experimental trials (ECC75, ECC150, ECC300 and Control – no exercise) with a 4-week washout period in-between. Performance and muscle damage, inflammatory and oxidative stress markers were evaluated at baseline, post-exercise, 24, 48 and 192 hours following each exercise protocol. Concentric and eccentric peak torque decreased similarly in ECC150 and ECC300 during the first 48 h of recovery (p < 0.05) but remained unaffected in ECC75. Countermovement jump indices decreased post-exercise and at 24 h in ECC150 and ECC300, with ECC300 inducing a more pronounced reduction (p < 0.05). Creatine kinase increased until 48 h of recovery in all trials and remained elevated up to 192 h only in ECC300 (p < 0.05). Delayed onset of muscle soreness increased, and knee-joint range of motion decreased in a volume-dependent manner during the first 48 h (p < 0.05). Likewise, a volume-dependent decline of glutathione and a rise of protein carbonyls was observed during the first 48 h of recovery (p < 0.05). Collectively, our results indicate that muscle damage and performance recovery following eccentric exercise is volume dependent, at least in lower limbs.

Long-term detraining reverses the improvement of lifelong exercise on skeletal muscle ferroptosis and inflammation in aging rats: fiber-type dependence of the Keap1/Nrf2 pathway.

We investigated the effects of lifelong aerobic exercise and 8months of detraining after 10months of aerobic training on circulation, skeletal muscle oxidative stress, and inflammation in aging rats. Sprague-Dawley rats were randomly assigned to the control (CON), detraining (DET), and lifelong aerobic training (LAT) groups. The DET and LAT groups began aerobic treadmill exercise at the age of 8months and stopped training at the 18th and 26th month, respectively; all rats were sacrificed when aged 26months. Compared with CON, LAT remarkably decreased serum and aged skeletal muscle 4-hydroxynonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. Superoxide dismutase 2(SOD2) levels were higher in the LAT group than in the CON group in skeletal muscle. However, DET remarkably decreased SOD2 protein expression and content in the skeletal muscle and increased malondialdehyde (MDA) level compared with LAT. Compared with LAT, DET remarkably downregulated adiponectin and upregulated tumor necrosis factor alpha (TNF-α) expression, while phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and 70-kDa ribosomal protein S6 kinase (P70S6K) protein expression decreased, and that of FoxO1 and muscle atrophy F-box (MAFbX) proteins increased in the quadriceps femoris. Adiponectin and TNF-α expression in the soleus muscle did not change between groups, whereas that of AKT, mammalian target of rapamycin (mTOR), and P70S6K was lower in the soleus in the DET group than in that in the LAT group. Compared with that in the LAT group, sestrin1 (SES1) and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the DET group was lower, whereas Keap1 mRNA expression was remarkably upregulated in the quadriceps femoris. Interestingly, the protein and mRNA levels of SES1, Nrf2, and Keap1 in soleus muscle did not differ between groups. LAT remarkably upregulated ferritin heavy polypeptide 1(FTH), glutathione peroxidase 4(GPX4), and solute carrier family 7member 11 (SLC7A11) protein expression in the quadriceps femoris and soleus muscles, compared with CON. However, compared with LAT, DET downregulated FTH, GPX4, and SLC7A11 protein expression in the quadriceps femoris and soleus muscles. Long-term detraining during the aging phase reverses the improvement effect of lifelong exercise on oxidative stress, inflammation, ferroptosis, and muscle atrophy in aging skeletal muscle. The quadriceps femoris is more evident than the soleus, which may be related to the different changes in the Keap1/Nrf2 pathway in different skeletal muscles.

Effects of L-Carnitine Intake on Exercise-Induced Muscle Damage and Oxidative Stress: A Narrative Scoping Review.

Exercise-induced muscle damage results in decreased physical performance that is accompanied by an inflammatory response in muscle tissue. The inflammation process occurs with the infiltration of phagocytes (neutrophils and macrophages) that play a key role in the repair and regeneration of muscle tissue. In this context, high intensity or long-lasting exercise results in the breakdown of cell structures. The removal of cellular debris is performed by infiltrated phagocytes, but with the release of free radicals as collateral products. L-carnitine is a key metabolite in cellular energy metabolism, but at the same time, it exerts antioxidant actions in the neuromuscular system. L-carnitine eliminates reactive oxygen and nitrogen species that, in excess, alter DNA, lipids and proteins, disturbing cell function. Supplementation using L-carnitine results in an increase in serum L-carnitine levels that correlates positively with the decrease in cell alterations induced by oxidative stress situations, such as hypoxia. The present narrative scoping review focuses on the critical evaluation of the efficacy of L-carnitine supplementation on exercise-induced muscle damage, particularly in postexercise inflammatory and oxidative damage. Although both concepts appear associated, only in two studies were evaluated together. In addition, other studies explored the effect of L-carnitine in perception of fatigue and delayed onset of muscle soreness. In view of the studies analyzed and considering the role of L-carnitine in muscle bioenergetics and its antioxidant potential, this supplement could help in postexercise recovery. However, further studies are needed to conclusively clarify the mechanisms underlying these protective effects.

The persistence of stress-induced physical inactivity in rats: an investigation of central monoamine neurotransmitters and skeletal muscle oxidative stress.

Sedentary lifestyles have reached epidemic proportions world-wide. A growing body of literature suggests that exposures to adverse experiences (e.g., psychological traumas) are a significant risk factor for the development of physically inactive lifestyles. However, the biological mechanisms linking prior stress exposure and persistent deficits in physical activity engagement remains poorly understood. The purpose of this study was twofold. First, to identify acute stress intensity thresholds that elicit long-term wheel running deficits in rats. To that end, young adult male rats were exposed to a single episode of 0, 50, or 100 uncontrollable tail shocks and then given free access to running wheels for 9 weeks. Second, to identify stress-induced changes to central monoamine neurotransmitters and peripheral muscle physiology that may be maladaptive to exercise output. For this study, rats were either exposed to a single episode of uncontrollable tail shocks (stress) or left undisturbed in home cages (unstressed). Eight days later, monoamine-related neurochemicals were quantified by ultra-high performance liquid chromatography (UHPLC) across brain reward, motor, and emotion structures immediately following a bout of graded treadmill exercise controlled for duration and intensity. Additionally, protein markers of oxidative stress, inflammation, and metabolic activity were assessed in the gastrocnemius muscle by Western blot. For experiment 1, stress exposure caused a shock number-dependent two to fourfold decrease in wheel running distance across the entire duration of the study. For experiment 2, stress exposure curbed an exercise-induced increase of dopamine (DA) turnover measures in the prefrontal cortex and hippocampus, and augmented serotonin (5HT) turnover in the hypothalamus and remaining cortical area. However, stress exposure also caused several monoaminergic changes independent of exercise that could underlie impaired motivation for physical activity, including a mild dopamine deficiency in the striatal area. Finally, stress potently increased HSP70 and lowered SOD2 protein concentrations in the gastrocnemius muscle, which may indicate prolonged oxidative stress. These data support some of the possible central and peripheral mechanisms by which exposure to adverse experiences may chronically impair physical activity engagement.

The role of the microcirculation and integrative cardiovascular physiology in the pathogenesis of ICU-acquired weakness.

Skeletal muscle dysfunction after critical illness, defined as ICU-acquired weakness (ICU-AW), is a complex and multifactorial syndrome that contributes significantly to long-term morbidity and reduced quality of life for ICU survivors and caregivers. Historically, research in this field has focused on pathological changes within the muscle itself, without much consideration for their in vivo physiological environment. Skeletal muscle has the widest range of oxygen metabolism of any organ, and regulation of oxygen supply with tissue demand is a fundamental requirement for locomotion and muscle function. During exercise, this process is exquisitely controlled and coordinated by the cardiovascular, respiratory, and autonomic systems, and also within the skeletal muscle microcirculation and mitochondria as the terminal site of oxygen exchange and utilization. This review highlights the potential contribution of the microcirculation and integrative cardiovascular physiology to the pathogenesis of ICU-AW. An overview of skeletal muscle microvascular structure and function is provided, as well as our understanding of microvascular dysfunction during the acute phase of critical illness; whether microvascular dysfunction persists after ICU discharge is currently not known. Molecular mechanisms that regulate crosstalk between endothelial cells and myocytes are discussed, including the role of the microcirculation in skeletal muscle atrophy, oxidative stress, and satellite cell biology. The concept of integrated control of oxygen delivery and utilization during exercise is introduced, with evidence of physiological dysfunction throughout the oxygen delivery pathway - from mouth to mitochondria - causing reduced exercise capacity in patients with chronic disease (e.g., heart failure, COPD). We suggest that objective and perceived weakness after critical illness represents a physiological failure of oxygen supply-demand matching - both globally throughout the body and locally within skeletal muscle. Lastly, we highlight the value of standardized cardiopulmonary exercise testing protocols for evaluating fitness in ICU survivors, and the application of near-infrared spectroscopy for directly measuring skeletal muscle oxygenation, representing potential advancements in ICU-AW research and rehabilitation.

Modeling Human Muscular Dystrophies in Zebrafish: Mutant Lines, Transgenic Fluorescent Biosensors, and Phenotyping Assays.

Muscular dystrophies (MDs) are a heterogeneous group of myopathies characterized by progressive muscle weakness leading to death from heart or respiratory failure. MDs are caused by mutations in genes involved in both the development and organization of muscle fibers. Several animal models harboring mutations in MD-associated genes have been developed so far. Together with rodents, the zebrafish is one of the most popular animal models used to reproduce MDs because of the high level of sequence homology with the human genome and its genetic manipulability. This review describes the most important zebrafish mutant models of MD and the most advanced tools used to generate and characterize all these valuable transgenic lines. Zebrafish models of MDs have been generated by introducing mutations to muscle-specific genes with different genetic techniques, such as (i) N-ethyl-N-nitrosourea (ENU) treatment, (ii) the injection of specific morpholino, (iii) tol2-based transgenesis, (iv) TALEN, (v) and CRISPR/Cas9 technology. All these models are extensively used either to study muscle development and function or understand the pathogenetic mechanisms of MDs. Several tools have also been developed to characterize these zebrafish models by checking (i) motor behavior, (ii) muscle fiber structure, (iii) oxidative stress, and (iv) mitochondrial function and dynamics. Further, living biosensor models, based on the expression of fluorescent reporter proteins under the control of muscle-specific promoters or responsive elements, have been revealed to be powerful tools to follow molecular dynamics at the level of a single muscle fiber. Thus, zebrafish models of MDs can also be a powerful tool to search for new drugs or gene therapies able to block or slow down disease progression.

A novel small molecule inhibitor of vascular endothelin signaling and hypertension

Augmented endothelin-1 (ET-1) signaling causes profound vasoconstriction, smooth muscle proliferation, endothelial dysfunction, oxidative stress, and vascular inflammation and sensitivity, which are often present in resistant hypertension, salt-sensitive hypertension and hypertension among African Americans. Here, we sought to examine the role of indole-3 acetic acid (IAA) as a novel inhibitor of vascular ET-1 signaling and hypertension. IAA, popularly known as auxin, is the most potent plant growth hormone, which is also produced in the human body via tryptophan metabolism by gut microbiota. Although the role of IAA as a potent plant growth hormone has been characterized, little is known about the biological activity of this compound in humans. Importantly, studies on the role of IAA as a regulator of arterial contractility, vascular inflammation and hypertension remain completely unexplored. Our data demonstrates that IAA inhibits ET-1-evoked vasoconstriction in resistance mesenteric arteries, ROS production in human aortic SMCs, expression of adhesion molecule VCAM-1 on EC surface, leukocyte adhesion, and ECE-1 activity. IAA dose-dependently inhibits the activity of a purified human endothelin converting enzyme-1 (ECE-1) that converts the precursor big ET to its active form ET-1 and is upregulated in hypertension. Consistent with these findings, we show that treatment of Dahl salt-sensitive (DSS) hypertensive rats, a model of augmented ET-1 signaling, with an oral extended-release, in situ gel-based formulation of IAA (IAA-oragel) reduces blood pressure (BP) elevation, suggesting a key role for IAA in BP regulation. Taken together, this study presents a novel inquiry into regulation of ET-1 function by IAA and could identify IAA as the first dual action inhibitor of the ET system. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Atenolol Ameliorates Skeletal Muscle Atrophy and Oxidative Stress Induced by Cast Immobilization in Rats.

(1) Background: Skeletal muscle atrophy is a common and debilitating condition associated with disease, bed rest, and inactivity. We aimed to investigate the effect of atenolol (ATN) on cast immobilization (IM)-induced skeletal muscle loss. (2) Methods: Eighteen male albino Wistar rats were divided into three groups: a control group, an IM group (14 days), and an IM+ATN group (10 mg/kg, orally for 14 days). After the last dose of atenolol, forced swimming test, rotarod test, and footprint analysis were performed, and skeletal muscle loss was determined. Animals were then sacrificed. Serum and gastrocnemius (GN) muscles were then collected, serum creatinine, GN muscle antioxidant, and oxidative stress levels were determined, and histopathology and 1H NMR profiling of serum metabolites were performed. (3) Results: Atenolol significantly prevented immobilization-induced changes in creatinine, antioxidant, and oxidative stress levels. Furthermore, GN muscle histology results showed that atenolol significantly increased cross-sectional muscle area and Feret's diameter. Metabolomics profiling showed that glutamine-to-glucose ratio and pyruvate, succinate, valine, citrate, leucine, isoleucine, phenylalanine, acetone, serine, and 3-hydroxybutyrate levels were significantly higher, that alanine and proline levels were significantly lower in the IM group than in the control group, and that atenolol administration suppressed these metabolite changes. (4) Conclusions: Atenolol reduced immobilization-induced skeletal muscle wasting and might protect against the deleterious effects of prolonged bed rest.

3.5 GHz radiofrequency radiation may affect biomechanics of bone and muscle of diabetics

With the developments in wireless technologies, living beings are increasingly exposed to electromagnetic fields (EMFs). EMFs are known to affect bone metabolism and muscle tissue. However, their effects on bones and skeletal muscles are controversial, as some studies have reported positive effects while others have reported adverse effects. In this study, the effects of radiofrequency radiation (RFR) on bone biomechanics and skeletal muscle tissues were investigated in diabetic and healthy rats. Rats were exposed to 3.5 GHz RFR for 2 h per day for 30 days. Bone biomechanics measurements were taken to evaluate the effects of RFR on bone quality, flexibility and durability. The whole-body specific absorption rate (SAR) was found to be 37 mW/kg. The results showed that RFR exposure had adverse effects on bone biomechanics, including decreased elasticity coefficient and Young’s modulus, increased maximum displacement and decreased maximum force. However, oxidative stress parameters in diabetics were also altered by 3.5 GHz RFR to a greater extent than in healthy rats. In conclusion, 3.5 GHz RFR may have potential to alter bone quality and structural integrity including muscle oxidative stress parameters in rats. It should be emphasized that the observed changes were more obvious in diabetic rats. In addition, the changes observed in healthy and diabetic rats exposed to RFR showed a statistically significant difference according to the sham groups.

Impact of dietary supplementation with Cinnamomum cassia essential oil on silver catfish (Rhamdia quelen): Toxicological effects and muscle antioxidant and fatty acid profiles

ABSTRACT The aim of this study was to determine the biological effects of dietary supplementation with 0.05% and 0.1% cinnamon essential oil extracted from Cinnamomum cassia on silver catfish (Rhamdia quelen). The final body weight, weight gain, and specific growth rate were significantly higher in fish supplemented with 0.05% cinnamon essential oil than in the control(untreated) group. Muscle reactive oxygen species and lipid peroxidation levels were significantly lower in fish supplemented with 0.05% cinnamon essential oil but higher at the 0.1% concentration. Muscle antioxidant capacity against peroxyl radicals (ACAP) and superoxide dismutase activity were significantly higher in fish supplemented with 0.05% cinnamon essential oil, while ACAP levels were lower in fish supplemented with 0.1%. The total saturated fatty acid content was significantly higher in the muscle of supplemented fish than in controls, while the total monounsaturated fatty acid content was significantly higher only in fish fed 0.1% cinnamon essential oil. Finally, the total content of polyunsaturated fatty acids was significantly lower in fish fed 0.1% essential oil. Thus, data demonstrated that 0.05% C. cassia essential oil improves fish health by improving performance and muscle oxidant/antioxidant status. Higher doses of cinnamon essential oil produced oxidative stress in muscle, suggesting toxicity at the 0.1% level. Although this cinnamon essential oil diet exerted positive health effects, this diet impaired the muscle fatty acid profile, suggesting adverse impacts on human health.

Effects of dietary disodium fumarate supplementation on muscle quality, chemical composition, oxidative stress and lipid metabolism of Hu sheep induced by high concentrate diet

Long-term feeding of high-concentrate (HC) diet causes the decrease of rumen pH, and induces subacute rumen acidosis (SARA), which results in metabolic disorders in sheep. This not only reduces animal performance, but also increases the risk of oxidative stress and inflammatory reaction. Disodium fumarate can improve the rumen buffering capacity and increase rumen pH. This experiment was conducted to investigate the effects of high concentrate diet on muscle quality, chemical composition, oxidative damage and lipid metabolism of Hu sheep, and the regulating effect of disodium fumarate. The results showed that HC diet induced SARA by reducing rumen pH value, thus causing oxidative stress and lipid metabolism disorder in longissimus lumborum (LL) muscle of Hu sheep, which also reduced meat quality by increasing shear force, drip loss, cooking loss, chewiness and hardness, and reducing the contents of crude fat and crude protein in LL muscle. However, disodium fumarate can improve meat quality of SARA Hu sheep by regulating rumen pH, inhibiting muscle oxidative stress and promoting lipid metabolism.

RNF7 Induces Skeletal Muscle Cell Apoptosis and Arrests Cell Autophagy via Upregulation of THBS1 and Inactivation of the PI3K/Akt Signaling Pathway in a Rat Sepsis Model.

Recently, long noncoding RNAs (lncRNAs) have been highlighted for extensive functionality in sepsis. In this study, we aimed to explore the role of RNF7 in the progression of sepsis. We initially established a rat model of sepsis through cecal ligation and puncture induction, whereupon RNF7 expression was determined by RT-qPCR. Following adenovirus infection, the role of RNF7 in muscle injury, skeletal muscle protein metabolism, oxidative stress, and inflammation in sepsis rats was analyzed. Then, downstream mechanisms of RNF7 were identified and validated. Further, lipopolysaccharide was applied to treat myoblast to further demonstrate the in vitro role of RNF7. Our results showed that RNF7 expression was upregulated during sepsis. Overexpression of RNF7 worsened the sepsis-induced skeletal muscle injury, induced skeletal muscle protein metabolism, oxidative stress, and inflammation in sepsis rats. Meanwhile, overexpression of RNF7 elevated thrombospondin-1 (THBS1) expression. Silencing of RNF7 inhibited THBS1 and activated the PI3K/Akt signaling pathway, arresting the release of inflammatory factors and oxidative stress levels in skeletal muscle cells. Altogether, RNF7 may promote skeletal muscle cell apoptosis while simultaneously inhibiting cell autophagy through the promotion of THBS1 and inactivation of the PI3K/Akt signaling pathway.

Nuclear Factor Erythroid 2-Related Factor 2 and Its Targets in Skeletal Muscle Repair and Regeneration.

Significance: Skeletal muscles have a robust regenerative capacity in response to acute and chronic injuries. Muscle repair and redox homeostasis are intimately linked; increased generation of reactive oxygen species leads to cellular dysfunction and contributes to muscle wasting and progression of muscle diseases. In exemplary muscle disease, Duchenne muscular dystrophy (DMD), caused by mutations in the DMD gene that encodes the muscle structural protein dystrophin, the regeneration machinery is severely compromised, while oxidative stress contributes to the progression of the disease. The nuclear factor erythroid 2-related factor 2 (NRF2) and its target genes, including heme oxygenase-1 (HO-1), provide protective mechanisms against oxidative insults. Recent Advances: Relevant advances have been evolving in recent years in understanding the mechanisms by which NRF2 regulates processes that contribute to effective muscle regeneration. To this end, pathways related to muscle satellite cell differentiation, oxidative stress, mitochondrial metabolism, inflammation, fibrosis, and angiogenesis have been studied. The regulatory role of NRF2 in skeletal muscle ferroptosis has been also suggested. Animal studies have shown that NRF2 pathway activation can stop or reverse skeletal muscle pathology, especially when endogenous stress defence mechanisms are imbalanced. Critical Issues: Despite the growing recognition of NRF2 as a factor that regulates various aspects of muscle regeneration, the mechanistic impact on muscle pathology in various models of muscle injury remains imprecise. Future Directions: Further studies are necessary to fully uncover the role of NRF2 in muscle regeneration, both in physiological and pathological conditions, and to investigate the possibilities for development of new therapeutic modalities. Antioxid. Redox Signal. 38, 619-642.

Muscle Oxidative Stress Plays a Role in Hyperthyroidism-Linked Insulin Resistance

While a low level of ROS plays a role in cellular regulatory processes, a high level can lead to oxidative stress and cellular dysfunction. Insulin resistance (IR) is one of the dysfunctions in which oxidative stress occurs and, until now, the factors underlying the correlation between oxidative stress and IR were unclear and incomplete. This study aims to explore this correlation in skeletal muscle, a tissue relevant to insulin-mediated glucose disposal, using the hyperthyroid rat as a model of oxidative stress. The development of IR in the liver from hyperthyroid animals has been widely reported, whereas data concerning the muscle are quite controversial. Thus, we investigated whether hyperthyroidism induces IR in skeletal muscle and the role of oxidative stress in this process. Particularly, we compared the effects of hyperthyroidism on IR both in the absence and presence of vitamin E (Vit E), acting as an antioxidant. Putative correlations between ROS production, oxidative stress markers, antioxidant capacity and changes in intracellular signalling pathways related to insulin action (AKT) and cellular stress response (EIF2α; JNK; PGC1α; BIP; and NRF1) were investigated. Moreover, we assessed the effects of hyperthyroidism and Vit E on the expression levels of genes encoding for glucose transporters (Slc2a1; Slc2a4), factors involved in lipid homeostasis and insulin signalling (Pparg; Ppara, Cd36), as well as for one of the IR-related inflammatory factors, i.e., interleukin 1b (Il1b). Our results suggest that hyperthyroidism-linked oxidative stress plays a role in IR development in muscle and that an adequate antioxidant status, obtained by vitamin E supplementation, that mitigates oxidative stress, may prevent IR development.

Impacts of microgravity on amino acid metabolism during spaceflight.

Spaceflight exerts an extreme and unique influence on human physiology as astronauts are subjected to long-term or short-term exposure to microgravity. During spaceflight, a multitude of physiological changes, including the loss of skeletal muscle mass, bone resorption, oxidative stress, and impaired blood flow, occur, which can affect astronaut health and the likelihood of mission success. In vivo and in vitro metabolite studies suggest that amino acids are among the most affected nutrients and metabolites by microgravity (a weightless condition due to very weak gravitational forces). Moreover, exposure to microgravity alters gut microbial composition, immune function, musculoskeletal health, and consequently amino acid metabolism. Appropriate knowledge of daily protein consumption, with a focus on specific functional amino acids, may offer insight into potential combative and/or therapeutic effects of amino acid consumption in astronauts and space travelers. This will further aid in the successful development of long-term manned space mission and permanent space habitats.