Free radical-mediated skeletal muscle dysfunction in inflammatory conditions

2007 ◽  
Vol 102 (5) ◽  
pp. 2056-2063 ◽  
Author(s):  
Gerald S. Supinski ◽  
Leigh A. Callahan
Keyword(s):  
Skeletal Muscle ◽  
Free Radicals ◽  
Free Radical ◽  
Muscle Weakness ◽  
Muscle Function ◽  
Muscle Dysfunction ◽  
Radical Species ◽  
Inflammatory Conditions ◽  
Skeletal Muscle Dysfunction ◽  
Free Radical Species

Loss of functional capacity of skeletal muscle is a major cause of morbidity in patients with a number of acute and chronic clinical disorders, including sepsis, chronic obstructive pulmonary disease, heart failure, uremia, and cancer. Weakness in these patients can manifest as either severe limb muscle weakness (even to the point of virtual paralysis), respiratory muscle weakness requiring mechanical ventilatory support, and/or some combination of these phenomena. While factors such as nutritional deficiency and disuse may contribute to the development of muscle weakness in these conditions, systemic inflammation may be the major factor producing skeletal muscle dysfunction in these disorders. Importantly, studies conducted over the past 15 years indicate that free radical species (superoxide, hydroxyl radicals, nitric oxide, peroxynitrite, and the free radical-derived product hydrogen peroxide) play an key role in modulating inflammation and/or infection-induced alterations in skeletal muscle function. Substantial evidence exists indicating that several free radical species can directly alter contractile protein function, and evidence suggests that free radicals also have important effects on sarcoplasmic reticulum function, on mitochondrial function, and on sarcolemmal integrity. Free radicals also modulate activation of several proteolytic pathways, including proteosomally mediated protein degradation and, at least theoretically, may also influence pathways of protein synthesis. As a result, free radicals appear to play an important role in regulating a number of downstream processes that collectively act to impair muscle function and lead to reductions in muscle strength and mass in inflammatory conditions.

scholarly journals Skeletal muscle dysfunction in chronic renal failure: effects of exercise

2006 ◽  
Vol 290 (4) ◽  
pp. F753-F761 ◽  
Author(s):  
Gregory R. Adams ◽  
Nosratola D. Vaziri
Keyword(s):  
Skeletal Muscle ◽  
Renal Failure ◽  
Exercise Capacity ◽  
Muscle Function ◽  
Chronic Illnesses ◽  
Treatment Modalities ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction

A number of chronic illnesses such as renal failure (CRF), obstructive pulmonary disease, and congestive heart failure result in a significant decrease in exercise tolerance. There is an increasing awareness that prescribed exercise, designed to restore some level of physical performance and quality of life, can be beneficial in these conditions. In CRF patients, muscle function can be affected by a number of direct and indirect mechanisms caused by renal disease as well as various treatment modalities. The aims of this review are twofold: first, to briefly discuss the mechanisms by which CRF negatively impacts skeletal muscle and, therefore, exercise capacity, and, second, to discuss the available data on the effects of programmed exercise on muscle function, exercise capacity, and various other parameters in CRF.

scholarly journals Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction

2016 ◽  
Vol 311 (2) ◽  
pp. E293-E301 ◽  
Author(s):  
Laura A. A. Gilliam ◽  
Daniel S. Lark ◽  
Lauren R. Reese ◽  
Maria J. Torres ◽  
Terence E. Ryan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cancer Chemotherapy ◽  
Protein Oxidation ◽  
Muscle Function ◽  
Contractile Function ◽  
Muscle Dysfunction ◽  
Skeletal Muscle Dysfunction ◽  
Whole Muscle ◽  
Loss Of Strength ◽  
Mitochondrial Respiratory

The loss of strength in combination with constant fatigue is a burden on cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy drug used in the clinic, causes skeletal muscle dysfunction and increases mitochondrial H2O2. We hypothesized that the combined effect of cancer and chemotherapy in an immunocompetent breast cancer mouse model (E0771) would compromise skeletal muscle mitochondrial respiratory function, leading to an increase in H2O2-emitting potential and impaired muscle function. Here, we demonstrate that cancer chemotherapy decreases mitochondrial respiratory capacity supported with complex I (pyruvate/glutamate/malate) and complex II (succinate) substrates. Mitochondrial H2O2-emitting potential was altered in skeletal muscle, and global protein oxidation was elevated with cancer chemotherapy. Muscle contractile function was impaired following exposure to cancer chemotherapy. Genetically engineering the overexpression of catalase in mitochondria of muscle attenuated mitochondrial H2O2 emission and protein oxidation, preserving mitochondrial and whole muscle function despite cancer chemotherapy. These findings suggest mitochondrial oxidants as a mediator of cancer chemotherapy-induced skeletal muscle dysfunction.

scholarly journals Ultrasonic Elastography of the Rectus Femoris, a Potential Tool to Predict Sarcopenia in Patients With Chronic Obstructive Pulmonary Disease

2022 ◽  
Vol 12 ◽  
Author(s):  
Mingming Deng ◽  
Xiaoming Zhou ◽  
Yanxia Li ◽  
Yan Yin ◽  
Chaonan Liang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Physical Function ◽  
Muscle Function ◽  
Rectus Femoris ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Tnf Α ◽  
Potential Tool

Purpose: Skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. Abnormal muscle quantity of the lower limbs is a manifestation of skeletal muscle dysfunction in patients with COPD. Shear wave ultrasound elastography (SWE) is a novel and possible tool to evaluate qualitative muscle parameters. This study explores the feasibility of SWE to measure the stiffness of the rectus femoris and evaluates its value in predicting sarcopenia in patients with COPD.Methods: Ultrasound examination of the rectus femoris was performed to determine the mean elasticity index (SWEmean), cross-sectional area (RFcsa), and thickness (RFthick) using grayscale ultrasonography (US) and SWE in 53 patients with COPD and 23 age-matched non-COPD healthy controls. The serum levels of circulating biomarkers (GDF15, resistin, and TNF-α) were measured using ELISA. The definition of sarcopenia followed the guidelines from the Asian Working Group for Sarcopenia. Receiver operating characteristic (ROC) curve analysis of the SWEmean, RFthick, and RFcsa was used to evaluate their predictive ability for sarcopenia.Results: The intraobserver and interobserver repeatability of SWE performance was excellent (all correlation coefficients > 0.95; p < 0.05). The SWEmean of the rectus femoris in patients with COPD (8.98 ± 3.12 kPa) was decreased compared with that in healthy controls (17.00 ± 5.14 kPa) and decreased with advanced global initiative for chronic obstructive lung disease (GOLD) stage. Furthermore, SWEmean was found to be independent of sex, height, and body mass, and a lower SWEmean in patients with COPD was positively associated with reduced pulmonary function, worse physical function, poor exercise tolerance, decreased muscle strength, and worse dyspnea index score. The correlation between physical function [five-repetition sit-to-stand test (5STST)], muscle function, and SWEmean was higher than those of RFthick and RFcsa. In addition, SWEmean was negatively correlated with serum GDF15 levels (r = −0.472, p < 0.001), serum resistin levels (r = −0.291, p = 0.035), and serum TNF-α levels (r = −0.433, p = 0.001). Finally, the predictive power of SWEmean [area under the curve (AUC): 0.863] in the diagnosis of sarcopenia was higher than that of RFthick (AUC: 0.802) and RFcsa (AUC: 0.816).Conclusion: Compared with grayscale US, SWE was not affected by the patient’s height, weight, or BMI and better represented skeletal muscle function and physical function. Furthermore, SWE is a promising potential tool to predict sarcopenia in patients with COPD.

scholarly journals Measuring skeletal muscle strength and endurance, from bench to bedside

2008 ◽  
Vol 31 (5) ◽  
pp. 307 ◽  
Author(s):  
Didier Saey ◽  
Thierry Troosters
Keyword(s):  
Skeletal Muscle ◽  
Muscle Strength ◽  
Exercise Training ◽  
Muscle Weakness ◽  
Muscle Function ◽  
Muscle Endurance ◽  
Muscle Dysfunction ◽  
Skeletal Muscle Function ◽  
Peripheral Muscle ◽  
Skeletal Muscle Strength

Peripheral muscle dysfunction is a recognized and important systemic consequence of many chronic diseases. Peripheral muscle weakness is associated with excess utilization of health care recourses, morbidity and /or mortality in patients with COPD, congestive heart failure, liver and frail elderly. In the latter group, muscle weakness was associated with significant increase in falling and falling related injury. Exercise training does enhance skeletal muscle function and exercise performance. In addition, patients who start a training program with impaired skeletal muscle function may be more likely to respond adequately to an exercise training program. It is beyond the scope of the present review to discuss in detail the factors that may contribute to muscle dysfunction in chronic conditions. Clearly, muscle weakness is multi-factorial. Factors associated with skeletal muscle force are general factors (such as age, body weight, sex), disease related factors (such as inactivity) and disease specific factors (for example in COPD drug treatment, i.e. corticosteroid treatment, inflammation, oxidative stress and hypoxia have been shown to contribute to muscle dysfunction). This review will focus on the different ways to assess skeletal muscle function in patients with chronic disease. More specifically, techniques to assess skeletal muscle strength, skeletal muscle endurance and skeletal muscle fatigue will be discussed. For the American College of Sport Medicine (ACSM) not only muscle strength but also muscle endurance are health- related fitness components. Loss in one of these muscle characteristics results in impaired muscle. Muscle function tests are very specific to the muscle group tested, the type of contraction, the velocity of muscle motion, the type of equipment and the joint range of motion. Results of any test are specific to the procedures used. Individuals should participate in familiarization sessions with the equipment, and adhere to a specific protocol in order to obtain a true and reliable score. A change in one’s muscular fitness over time can be based on the absolute value of the external force (Newton (N)), but when comparisons are made between individuals, the values should be expressed as relative values (percentage of a predicted normal value). In both cases, caution must be taken in the interpretation of the result because the norms may not include a representative sample of the individual being measured, a standardized protocol may be absent, or the exact test being used may differ.

141 Mild Burns Combined with Diet Induced Demyelination Does Not Affect Skeletal Muscle Function

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S94-S94
Author(s):  
Emre Vardarli ◽  
Nisha Bhattarai ◽  
Amina El Ayadi ◽  
Y E Wang ◽  
Jayson W Jay ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Diet Group ◽  
Muscle Dysfunction ◽  
Skeletal Muscle Function ◽  
Regular Diet ◽  
Skeletal Muscle Dysfunction ◽  
Significant Difference ◽  
The Impact

Abstract Introduction Severe burns result in decreased skeletal muscle mass and function. Recent evidence suggests that massive burns disrupt the motor-neural system including motor neurons to partially explain skeletal muscle dysfunction in response to burns. However, impact of demyelination on burn induced skeletal muscle dysfunction has not been investigated. The purpose of this study was to determine the impact of exaggerated demyelination on skeletal muscle dysfunction after burn. Methods C57BL/6 (20-25g, male, n = 26) mice were separated into 6 groups (4–5 animals per group) by diet, burn injury and timepoint (burn or sham groups with two different diets measured at two different timepoints). Mice were fed with either cuprizone diet (0.2 %) to induce severe demyelination or regular diet (18 % protein) for 5 weeks prior to injury. Burns were administered by immersing the dorsal side of the animal into ~95 °C hot water for 10 seconds (~15 % body surface area, full thickness burn). In-situ gastrocnemius function was assessed by attaching the distal tendon of the muscle to a lever arm of a force transducer and stimulating the muscle via exposed sciatic nerve while the animal was under anesthesia. In-situ gastrocnemius muscle function was evaluated 3- and 7-days after burn. Results Food intake was 30 % higher in cuprizone diet group compared to the regular diet group (p=0.002). However, there was no significant difference in body weight among groups (p=0.071). No significant difference was found in gastrocnemius wet weight, peak twitch tension, time to reach peak twitch tension, peak twitch half relaxation time, force-frequency relationship, maximum tetanic force, and fatigue index among groups (burn effect, diet effect, time effect, and their interactions; NS). Conclusions Mild burns combined with demyelination by diet had no effect on skeletal muscle function on our timepoints, and 15 % TBSA burn size was not sufficient to induce skeletal muscle dysfunction. The impact of burn induced neural damage on muscle function and performance indicates further investigation.

scholarly journals Free radicals in skin and muscle: damaging agents or signals for adaptation?

1999 ◽  
Vol 58 (3) ◽  
pp. 673-676 ◽  
Author(s):  
Malcom J. Jackson
Keyword(s):  
Gene Expression ◽  
Free Radicals ◽  
Free Radical ◽  
Potential Role ◽  
Biological Effects ◽  
Cell Types ◽  
Radical Species ◽  
Free Radical Species ◽  
The Subject ◽  
Influence Gene Expression

Much of the current literature regarding the biological effects of antioxidant nutrients has concentrated on their potential role in inhibiting or preventing tissue damage induced by free radical species produced during metabolism. Recent findings indicate that antioxidants may also have more subtle roles, regulating changes in gene expression induced by oxidizing free radical species. There is increasing evidence that free radicals act as signals for cell adaptation in a variety of cell types and the nature of the mechanisms by which free radical species influence gene expression is the subject of much current research. Processes such as these may be particularly important in tissues regularly exposed to varying amounts of oxidative stress as part of their normal physiological functions. Examples of such tissues include skin exposed to u.v. light and skeletal muscle subjected to repeated bouts of exercise.

scholarly journals Pseudomonas aeruginosa Quorum Sensing Molecule Alters Skeletal Muscle Protein Homeostasis by Perturbing the Antioxidant Defense System

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Arunava Bandyopadhaya ◽  
A. Aria Tzika ◽  
Laurence G. Rahme
Keyword(s):  
Skeletal Muscle ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Muscle Function ◽  
Muscle Dysfunction ◽  
Chronic Infections ◽  
Skeletal Muscle Function ◽  
Content Type ◽  
Skeletal Muscle Dysfunction ◽  
Ros Homeostasis

ABSTRACT Skeletal muscle function is compromised in many illnesses, including chronic infections. The Pseudomonas aeruginosa quorum sensing (QS) signal, 2-amino acetophenone (2-AA), is produced during acute and chronic infections and excreted in human tissues, including the lungs of cystic fibrosis patients. We have shown that 2-AA facilitates pathogen persistence, likely via its ability to promote the formation of bacterial persister cells, and that it acts as an interkingdom immunomodulatory signal that epigenetically reprograms innate immune functions. Moreover, 2-AA compromises muscle contractility and impacts the expression of genes involved in reactive oxygen species (ROS) homeostasis in skeletal muscle and in mitochondrial functions. Here, we elucidate the molecular mechanisms of 2-AA’s impairment of skeletal muscle function and ROS homeostasis. Murine in vivo and differentiated C2C12 myotube cell studies showed that 2-AA promotes ROS generation in skeletal muscle via the modulation of xanthine oxidase (XO) activity, NAD(P)H oxidase2 (NOX2) protein level, and the activity of antioxidant enzymes. ROS accumulation triggers the activity of AMP-activated protein kinase (AMPK), likely upstream of the observed locations of induction of ubiquitin ligases Muscle RING Finger 1 (MuRF1) and Muscle Atrophy F-box (MAFbx), and induces autophagy-related proteins. The protein-level perturbation in skeletal muscle of silent mating type information regulation 2 homolog 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), and uncoupling protein 3 (UCP3) is rescued by the antioxidant N-acetyl-l-cysteine (NAC). Together, these results unveil a novel form of action of a QS bacterial molecule and provide molecular insights into the 2-AA-mediated skeletal muscle dysfunction caused by P. aeruginosa. IMPORTANCE Pseudomonas aeruginosa, a bacterium that is resistant to treatment, causes serious acute, persistent, and relapsing infections in humans. There is increasing evidence that bacterial excreted small molecules play a critical role during infection. We have shown that a quorum sensing (QS)-regulated excreted small molecule, 2-AA, which is abundantly produced by P. aeruginosa, promotes persistent infections, dampens host inflammation, and triggers mitochondrial dysfunction in skeletal muscle. QS is a cell-to-cell communication system utilized by bacteria to promote collective behaviors. The significance of our study in identifying a mechanism that leads to skeletal muscle dysfunction, via the action of a QS molecule, is that it may open new avenues in the control of muscle loss as a result of infection and sepsis. Given that QS is a common characteristic of prokaryotes, it is possible that 2-AA-like molecules promoting similar effects may exist in other pathogens.

An Investigation of Stable Free Radicals in Polyimides Using EPR Spectroscopy

1993 ◽  
Vol 305 ◽  
Author(s):  
Myong K. Ahn ◽  
Thomas C. Stringfellow ◽  
Jianming Lei ◽  
Kenneth J. Bowles ◽  
Michael Meador
Keyword(s):  
Free Radicals ◽  
Free Radical ◽  
Variable Temperature ◽  
Oxidative Degradation ◽  
High Strength ◽  
Radical Species ◽  
Stable Free Radical ◽  
Paramagnetic Resonance ◽  
Free Radical Species ◽  
Temperature Electron

AbstractPolyimide resins are used as matrix materials in fiber reinforced composites. Such composites are lightweight, have relatively high strength, and can be used at temperatures above 300°C. Postcured PMR-15 produces room temperature electron paramagnetic resonance (epr) spectra from stable free radical species formed during the postcuring stages. The variable temperature EPR spectral intensities indicate the presence of at least two free radical species. The thermo-oxidative degradation involves free radicals generated during the postcuring process in the presence of oxygen gas. These and other recent results including ENDOR and HYSCORE work are discussed.

Contractile activity-induced oxidative stress: cellular origin and adaptive responses

2001 ◽  
Vol 280 (3) ◽  
pp. C621-C627 ◽  
Author(s):  
A. McArdle ◽  
D. Pattwell ◽  
A. Vasilaki ◽  
R. D. Griffiths ◽  
M. J. Jackson
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Free Radical ◽  
Muscle Protein ◽  
Contractile Activity ◽  
Cellular Damage ◽  
Radical Species ◽  
Free Radical Species ◽  
Short Period

Previous studies have reported that oxidizing free radical species are generated during exercise, and there has been considerable interest in the potential effects of these on exercising tissues. We hypothesized that contracting skeletal muscle was a major source of oxidizing free radical species and that untrained skeletal muscle would adapt to the oxidative stress of a single short period of contractile activity by upregulation of the activity of cytoprotective proteins in the absence of overt cellular damage. Fifteen minutes of aerobic contractile activity was found to induce a rapid release of superoxide anions from mouse skeletal muscle in vivo, and studies with contracting cultured skeletal muscle myotubes confirmed that this was due to release from myocytes rather than other cell types present within muscle tissue in vivo. This increased oxidant production caused a rapid, transient reduction in muscle protein thiol content, followed by increases in the activities of superoxide dismutase and catalase and in content of heat shock proteins. These changes occurred in the absence of overt damage to the muscle cells.

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