Figure - available from: Journal of Muscle Research and Cell Motility
This content is subject to copyright. Terms and conditions apply.
Illustration picturing eccentric contraction-induced muscle damage In skeletal muscle undergoing eccentric contraction, a decline of force production is greater and require a longer period for recovery compared to concentric and isometric contractions. This is because of muscle damage, which is characterized by cleavage of various proteins, increased membrane permeability, efflux and influx of ions and proteins, and ultrastructural changes. CK, creatine kinase; DHPR, dihydropyridine receptor; JP, junctophilin; MHC, myosin heavy chain; RYR, ryanodine receptor; SR, sarcoplasmic reticulum; T, transverse
Source publication
Eccentric contraction (ECC) often results in large and long-lasting force deficits accompanied by muscle soreness, primarily due to muscle damage. In this sense, exercises that involve ECC are less desirable. Paradoxically, exercise training that includes a substantial eccentric phase leads to a more powerful activation of the genes responsible for...
Citations
... Although force typically recovers rapidly during the recovery period, contractions involving a substantial eccentric component often lead to prolonged force depression, which requires several days of recovery. This is primarily attributed to muscle damage characterized by myofibrillar integrity loss, excitation-contraction coupling failure, increased sarcolemmal permeability (membrane damage), muscle swelling, and delayed-onset muscular soreness (Hody et al. 2019;Kanzaki et al. 2022). ...
... Phagocytes play a critical role in clearing debris generated by ECC-induced mechanical and/or Ca 2+ stress and in subsequent regeneration (Peake et al. 2017;Kanzaki et al. 2022). However, excessive invasion triggers severe inflammation due to superoxide, NO, and cytokines released by these pro-inflammatory cells (Peake et al. 2017). ...
Eccentric contraction (ECC) has been shown to induce leukocyte invasion into skeletal muscle, resulting in muscle inflammation. This study aimed to investigate whether prior ingestion of L-arginine (ARG), a nitric oxide precursor, inhibits ECC-induced macrophage invasion. Male Wistar rats received ARG in water for 7 days, beginning 3 days prior to ECC. ECCs were induced in the anterior crural muscles for 200 cycles. Three days later, the tibialis anterior and extensor digitorum longus muscles were excised for biochemical analysis and force measurement, respectively. ARG ingestion increased nitrite and nitrate levels in plasma and muscle, inhibiting force depression and reducing CD68 content in muscles subjected to ECC. ARG ingestion also ameliorated an ECC-induced increase in protein nitration, although neither ARG ingestion nor ECC induction affected protein carbonyl levels. The present results suggest that ingestion of ARG or ARG-rich foods may alleviate inflammation by attenuating phagocyte invasion in eccentrically contracted skeletal muscles.
... Skeletal muscle expresses calpains 1, 2, and 3 35) . Of these, calpain 1 has been shown to be mainly involved in ECC-induced proteolysis, including the RyR 36) . Autolysis (digestion of an enzyme by the action of its enzyme) is an indicator of calpains, since it reduces the Ca 2+ concentration required for their activation. ...
The aim of this study was to elucidate the effects of oral administration of S-nitrosoglutathione (GSNO), a nitric oxide donor, on force production and Ca²⁺ regulatory proteins in fast-twitch muscles subjected to eccentric contraction (ECC). Rats were administered 1 mmol kg⁻¹ d⁻¹ GSNO for five days before ECC. Force production, sarcoplasmic reticulum (SR) Ca²⁺-ATPase activity, and amounts of Ca²⁺ regulatory proteins were examined after 200 ECC repetitions. Three days after ECC, the experimental extensor digitorum longus muscles and the contralateral resting muscles were quickly excised and used for the experiment. Force production at 20 Hz returned to resting levels in GSNO-treated muscles, but not in resting muscles. Western blot analysis showed that GSNO ingestion inhibited ECC-induced loss of ryanodine receptor (RyR) 1 responsible for SR Ca²⁺ release capacity. Overall, these findings indicate that oral administration of a nitric oxide donor prior to ECC can promote force recovery following ECC and suggest that this benefit may be due to inhibition of RyR proteolysis.
... This can be attributed to the fact, that ROS are generated, particularly in energy-demanding processes by mitochondria or during anaerobic metabolism while converting lactate to pyruvate (Hashimoto et al., 2007;Nikooie et al., 2021). Moreover, mechanical stress, especially due to eccentric resistance exercise is able to induce ROS-production since it causes diffusion of calcium ions in the sarcoplasm via stretch-activated channels (Kanzaki et al., 2022). Calcium ions are known to stimulate ROS-formation in mitochondria and xanthine oxidases (Kanzaki et al., 2022). ...
... Moreover, mechanical stress, especially due to eccentric resistance exercise is able to induce ROS-production since it causes diffusion of calcium ions in the sarcoplasm via stretch-activated channels (Kanzaki et al., 2022). Calcium ions are known to stimulate ROS-formation in mitochondria and xanthine oxidases (Kanzaki et al., 2022). Then, an imbalance in cellular redox-state can lead to LF-accumulation (Brunk & Terman, 2002;Höhn et al., 2011;Höhn & Grune, 2013). ...
... Resting phase between sets was 120 s and 180 s between exercises. To emphasize on eccentric muscle contractions which is associated with muscular damage and an increased oxidative stress (Kanzaki et al., 2022), which in turn potentially induced LF-accumulation (Höhn & Grune, 2013;Terman et al., 2010), in leg extension and leg press the movement pattern was conducted with a standardized cadence of 1 s in the concentric-and 2 s in the eccentric phase. ...
Lipofuscin (LF) is an intracellular aggregate associated with proteostatic impairments , especially prevalent in nondividing skeletal muscle fibers. Reactive oxygen species (ROS) drive LF-formation. Resistance training (RT) improves muscle performance but also increases ROS production, potentially promoting LF-formation. Thus, we aimed to investigate if RT of a mesocycle duration increases LF-formation in type-I and II muscle fibers and whether RT increases the antioxidant capacity (AOC) in terms of SOD1 and SOD2 content. An intervention group (IG) performed 14 eccentrically accented RT-sessions within 7 weeks. Vastus lateralis muscle biopsies were collected before and after the intervention from IG as well as from a control group (CG) which refrained from RT for the same duration. LF was predominantly found near nuclei, followed by membrane-near and a minor amount in the fiber core, with corresponding spot sizes. Overall, LF-content was higher in type-I than type-II fibers (p < 0.05). There was no increase in LF-content in type-I or IIA fibers, neither for the IG following RT nor for the CG. The same is valid for SOD1/2. We conclude that, in healthy subjects, RT can be safely performed, without adverse effects on increased LF-formation. K E Y W O R D S exercise, fiber types, human skeletal muscle, lipofuscin, SOD
... It is well known that exercise training that includes a substantial ECC induces a greater activation of the genes responsible for muscle remodeling than other types of training (Hody et al., 2019), owing to which the majority of competitive athletes employ high-intensity eccentric training regimens. On the contrary, mechanical stress due to a stretch with ECC and a myofibrillar contraction leads to structural perturbations, such as triad deformation and/or sarcomere inhomogeneity (Kanzaki et al., 2022). Additionally, calpain-induced degradation of proteins involved in excitation-contraction coupling occurs within a few minutes after the cessation of ECC (Zhang et al., 2008). ...
... Additionally, calpain-induced degradation of proteins involved in excitation-contraction coupling occurs within a few minutes after the cessation of ECC (Zhang et al., 2008). These changes often result in large and long-lasting force deficits in ECC muscle (Kanzaki et al., 2022). ...
The aim of this study was to elucidate the effects of eccentric contraction (ECC) on force enhancement in rat fast‐twitch skeletal muscle. Gastrocnemius (GAS) muscles were subjected to 200 ECCs in situ by electrical stimulation. Immediately before and after the stimulation, isometric torque produced by ankle flexion was measured at an ankle angle of 90°. After the second torque measurement, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analysis. ECC did not induce changes in the amount of degraded titin. After ECC, isometric torques in the GAS muscles were markedly reduced, especially at low stimulation frequency. ECC increased passive torque in whole muscle and passive force in skinned fibers. Passive force enhancement and the ratio of passive force to the maximal Ca ²⁺ ‐activated force, but not residual force enhancement, were augmented in the skinned fibers subjected to ECC. An ECC‐induced increase in titin‐based stiffness may contribute to the increased PFE. These results suggest that skeletal muscle is endowed with a force potentiation system that can attenuate ECC‐induced force reductions.
... Several authors have used antioxidant compounds to reduce oxidative stress induced by physical exercise [71,72], including interventions with fish oil [25][26][27][28]. Regarding redox parameters at the end of the non-linear strength training in our study, no changes in the plasma concentrations of iron, heme iron, and TEAC were observed as a result of the fish oil supplementation. ...
Herein, we investigated the effect of fish oil supplementation combined with a strength-training protocol, for 6 weeks, on muscle damage induced by a single bout of strength exercise in untrained young men. Sixteen men were divided into two groups, supplemented or not with fish oil, and they were evaluated at the pre-training period and post-training period. We investigated changes before and 0, 24, and 48 h after a single hypertrophic exercise session. Creatine kinase (CK) and lactate dehydrogenase (LDH) activities, plasma interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and the redox imbalance were increased in response to the single-bout session of hypertrophic exercises at baseline (pre-training period) and decreased during the post-training period in the control group due to the repeated-bout effect (RBE). The fish oil supplementation exacerbated this reduction and improved the redox state. In summary, our findings demonstrate that, in untrained young men submitted to a strength-training protocol, fish oil supplementation is ideal for alleviating the muscle injury, inflammation, and redox imbalance induced by a single session of intense strength exercises, highlighting this supplementation as a beneficial strategy for young men that intend to engage in strength-training programs.
Eccentric exercise (EE) may lead to skeletal muscle injury, including oxidative stress and inflammation induction. Ginsenoside Rg1, a glycosylated triterpene present in the traditional Chinese medicine ginseng, was previously shown to prevent the development of multiple diseases through the attenuation of oxidative stress and inflammation. Therefore, this article hopes to investigate whether Rg1 exhibits anti-oxidant and anti-inflammatory effects in eccentric exercise-induced muscle damage (EEIMD). Additionally, Adult male Wistar rats were intraperitoneally injected with Rg1 (20 or 40 mg/kg) every day before EE for 5 consecutive days. The impact of Rg1 administration on levels of serum creatine kinase was evaluated, followed by observation of histological muscle damage through H&E staining. To assess protein nitrotyrosylation, lipid peroxidation and leukocyte infiltration in rat skeletal muscles, the levels of nitrotyrosine, MDA and MPO protein were analysed through western blotting analysis. The inflammatory response was evaluated by detecting iNOS, COX-2, IL-1 β , IL-6, MCP-1 and TNF- α mRNA and protein levels in rat skeletal muscles. The regulation of Rg1 on the NF- κ B pathway was examined through the analysis of phosphorylated NF- κ B p65 and I κ B α protein levels. Result display, EE resulted in elevated serum creatine kinase levels, widespread leukocyte infiltration, and notable muscle cell vacuolization and fragmentation in muscles. Furthermore, EE increased nitrotyrosine, MDA, MPO, iNOS, COX-2, IL-1 β , IL-6, MCP-1, and TNF- α levels in rats. However, these changes were reversed by Rg1 treatment. Furthermore, EE-induced upregulation in phosphorylated NF- κ B p65 and I κ B α levels was counteracted by Rg1. Overall, ginsenoside Rg1 plays an anti-oxidant and anti-inflammatory role in EEIMD through suppressing this NF- κ B signaling pathway.
