Eccentric Exercise-induced Muscle Injury Research Articles

Ameliorative Effects of Caffeic Acid Phenethyl Ester on an Eccentric Exercise-Induced Skeletal Muscle Injury by Down-Regulating NF-κB Mediated Inflammation

Background and Purpose: Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, displays a variety of biological activities. The aim is to examine the protective effect and mechanisms of CAPE on an eccentric exercise-induced muscle injury model. Experimental Approach: An intermittent downhill eccentric exercise protocol was used. The oxidative tissue injury and expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), monocyte chemotactic protein-1 (MCP-1), and activation of nuclear factor-κB (NF-κB) were examined. CAPE was applied in a dose of 5 and 10 mg/kg/day, p.o. Key Results: The eccentric exercise induced remarkable skeletal muscle damage uncovered by a dramatic elevation of creatine kinase in the serum and severe degenerative myopathy. These pathophysiological changes were accompanied by an upregulation of the inflammatory responses including protein nitrotyrosylation, poly-ADP-ribose-polymerase (PARP) upregulation, lipid peroxidation as measured by malondialdehyde (MDA) formation, and leukocyte infiltration as measured by myeloperoxidase (MPO). The inflammatory responses primarily resulted from enhanced expression of COX2, iNOS, and production of IL-1ß and MCP-1, possibly through activation of NF-κB. All these pathological changes were suppressed by treatment of CAPE. Conclusions and Implications: Our results indicate that CAPE exhibits protective effects against eccentric exercise-induced skeletal muscle damage in rats by blocking the NF-κB-dependent activation of the inflammatory responses.

Eccentric Exercise Elicits Elevation of Resting Calcium in Skeletal Muscle. Periodic Acceleration Enhanced the Recovery

Eccentric exercise (EC) can cause transient muscle damage, including muscle injury, muscle protein release into the plasma, an acute-phase immune response, and a decrease of muscle performance. Periodic acceleration (pGz) is a novel treatment that stimulates nitric oxide (NO) production by cNOS. Male mice (25-32 g) were divided in 4 groups (5/group). Group A: non-exercised (control); Group B: EC (45 min downhill exercise); Group C: EC followed by 30 min of pGz at 480 cpm daily starting on day 0 for 10 days; Group D: EC followed by 30 min of pGz, treated with L-NAME, 4 days prior and 10 days after EC. Resting intracellular Ca2+ concentration ([Ca2+]rest) was measured in vivo using Ca2+ selective microelectrodes on days 0, 2, 4, 6, 8, and 10 after EC. In group A the average [Ca2+]rest was 1113.8 nM on day 0 and did not change on subsequent days. On days 0, 2, 4, 6, 8 and 10 [Ca2+]rest (in nM) in polarized-exercised muscle fibers in group B was 395±38, 381±35, 334±23, 295±39, 268±27, and 223±27. In group C (EC+pGz) [Ca2+]rest was 402±46, 304±26, 260±35, 145±16, 121±10 nM and 113±6, showing a significant difference from group B by day 2 and reached control by day 10. In group D (EC+pGz+LNAME) the beneficial effect of pGz on [Ca2+]rest was abolished. We conclude that EC induced a chronic elevation of [Ca2+]rest in skeletal muscle that lasted up to 10 days and that pGz was able to accelerate the return to normal [Ca2+] homeostasis following EC induced muscle injury. The salutary effect of pGz on [Ca2+]rest appears to be mediated by an increase in NO generation, since the NOS blocker, L-NAME, eliminated the effect of pGz on [Ca2+]rest after EC.

Low-Frequency Fatigue as an Indicator of Eccentric Exercise-Induced Muscle Injury: The Role of Vitamin E

This study investigates whether vitamin E can attenuate eccentric exercise-induced soleus muscle injury as indicated by the amelioration of in situ isometric force decline following a low-frequency fatigue protocol (stimulation at 4 Hz for 5 min) and the ability of the muscle to recover 3 min after the termination of the fatigue protocol. Adult male Wistar rats were divided into vitamin E-supplemented or placebo-supplemented groups studied at rest, immediately post-exercise or 48 h post-exercise. Daily dl-α-tocopheryl acetate intraperitoneal injections of 100 mg/kg body mass for 5 consecutive days prior to exercise doubled its plasma levels. Fatigue index and recovery index expressed as a percentage of the initial tension. FI at 0 h post- and 48 h post-exercise respectively was 88% ± 4.2% and 89% ± 6.8% in the vitamin E groups versus 76% ± 3% and 80% ± 11% in the placebo groups. RI was 99% ± 3.4% and 100% ± 6% in the vitamin E groups versus 82% ± 3.1% and 84% ± 5.9% in the placebo groups. Complementally to the traditionally recorded maximal force, low-frequency fatigue measures may be beneficial for assessing injury-induced decrease in muscle functionality.

Effect of 5-day vitamin E supplementation on muscle injury after downhill running in rats

Antioxidant supplementation has been suggested to prevent exercise-induced muscle injury, but the findings are inconsistent. The objective of this study was to investigate the potential protective role of vitamin E treatment against eccentric exercise-induced muscle injury by examining morphological and functional alterations in rat soleus muscle after downhill running as well as muscle injury markers in the blood. Sixty adult male Wistar rats were randomly assigned to vitamin E-treated or placebo-treated groups studied at rest, immediately post-exercise or 48h post-exercise (n=10 per group). Vitamin E was administered by daily intraperitoneal injections of 100mg/kg body mass of DL: -α-tocopheryl acetate for five consecutive days prior to exercise, resulting in the doubling of its plasma concentration. Downhill running resulted in significant (P<0.05) changes in all injury markers for the placebo-treated rats at 0 and 48h post-exercise. However, significantly smaller soleus muscle single-twitch tension (P (t)) and unfused (40Hz) tetanic force, and greater plasma creatine kinase (CK) and lactate dehydrogenase (LD) activities compared with the control were found only immediately post-exercise for the vitamin E-treated rats (P<0.05). Maximal tetanic force (P (o)) did not decline significantly compared to sedentary controls at neither time points measured. The vitamin E-treated rats had significantly (P<0.05) higher soleus muscle P (t) immediately post-exercise than the placebo-treated rats as well as lower plasma CK and LD activity 48h post-exercise. However, there was no difference in P (o) decline between groups at either time points measured. Vitamin E-treated rats had less pronounced morphological alterations in muscle in the immediate and 48-h post-exercise period. In conclusion, the effect of short-term vitamin E supplementation against eccentric exercise-induced muscle injury did not appear to be physiologically significant, because vitamin E failed to prevent the decline in the functional measure of P (o) compared to the placebo conditions.

Adenosine A3receptor stimulation induces protection of skeletal muscle from eccentric exercise-mediated injury

Effective therapy to reduce skeletal muscle injury associated with severe or eccentric exercise is needed. The purpose of this study was to determine whether adenosine receptor stimulation can mediate protection from eccentric exercise-induced muscle injury. Downhill treadmill exercise (-15 degrees ) was used to induce eccentric exercise-mediated skeletal muscle injury. Experiments were conducted in both normal wild-type (WT) mice and also in beta-sarcoglycan knockout dystrophic mice, animals that show an exaggerated muscle damage with the stress of exercise. In the vehicle-treated WT animals, eccentric exercise increased serum creatine kinase (CK) greater than 3-fold to 358.9 +/- 62.7 U/l (SE). This increase was totally abolished by stimulation of the A(3) receptor. In the dystrophic beta-sarcoglycan-null mice, eccentric exercise caused CK levels to reach 55,124 +/- 5,558 U/l. A(3) receptor stimulation in these animals reduced the CK response by nearly 50%. In the dystrophic mice at rest, 10% of the fibers were found to be damaged, as indicated by Evans blue dye staining. While this percentage was doubled after exercise, A(3) receptor stimulation eliminated this increase. Neither the A(1) receptor agonist 2-chloro-N(6)-cyclopentyladenosine (0.05 mg/kg) nor the A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (0.07 mg/kg) protected skeletal muscle from eccentric exercise injury in WT or dystrophic mice. The protective effect of adenosine A(3) receptor stimulation was absent in mice, in which genes for phospholipase C beta2/beta3 (PLCbeta2/beta3) and beta-sarcoglycan were deleted. The present study elucidates a new protective role of the A(3) receptor and PLCbeta2/beta3 and points to a potentially effective therapeutic strategy for eccentric exercise-induced skeletal muscle injury.

Effects of baseline serum levels of Se on markers of eccentric exercise‐induced muscle injury

Inflammation and oxidative stress have been implicated in the mechanism of eccentric exercise-induced muscle injury. This study examined whether baseline serum levels of selenium (Se), a trace element that participates in both antioxidant and anti-inflammatory systems, affects the overall response to injury. Thirteen males performed 36 maximal eccentric actions with the elbow flexors of the non-dominant arm on a motorized dynamometer. Venous blood samples were collected immediately before and after exercise at 2, 24, 48, 72 and 96 hours. Established indicators of muscle damage such as maximum isometric torque (MIT), range of motion (ROM), relaxed arm angle (RANG), flexed arm angle (FANG), arm circumference (CIRC), muscle soreness and serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined at the same time points. Baseline serum levels of Se were also measured. Complementary data regarding assessment of Se status were retrieved by the use of a semi-quantitative food frequency questionnaire. All measures changed significantly (p<0.05) after exercise. The main finding of this study was that baseline Se serum levels were associated inversely with CK, LDH and FANG and positively with MIT and ROM (p<0.05). These data suggest that beyond overt Se deficiency, suboptimal Se status possibly worsens muscle functional decrements subsequent to eccentric muscle contractions.

Effects of eccentric exercise-induced muscle injury on blood levels of platelet activating factor (PAF) and other inflammatory markers

It has been reported that exercise with eccentric contractions can induce damage and inflammation in human muscle tissue, the severity of which depends on the duration and the intensity of exercise. Platelet activating factor (PAF) is a potent inflammatory mediator implicated in a series of pathophysiological conditions. We sought to investigate the relationship between PAF and eccentric exercise induced muscle damage. Thirteen healthy, recreationally active male subjects (27.5+/-3.78 year) performed 36 maximum voluntary eccentric contractions on a motorized muscle dynamometer using the elbow flexor muscles of the non-dominant arm. Venous blood samples were collected immediately before and after exercise at 2, 24, 48, 72 and 96 h. PAF was isolated, purified and determined by a platelet aggregation assay. Serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive protein (CRP) and complement C3 (C3), plasma level of fibrinogen and whole blood level of leukocytes (and their subsets) were determined. Established indicators of muscle damage as maximum isometric torque (MIT), range of motion (ROM), relaxed arm angle (RANG), flexed arm angle (FANG), arm circumference (CIRC) and muscle soreness were also measured at the same time points. PAF, leukocytes, CK and LDH were elevated after exercise, while other biochemical parameters such as CRP, C3 and fibrinogen were unchanged. We also observed an inverse association between PAF and MIT and ROM, as well as a positive association with other markers of muscle injury, i.e. CK, LDH, FANG and CIRC (all P's<0.05). Our findings may imply a role for PAF in the mechanism of eccentric exercise induced muscle damage.

Early assessment of exercise induced skeletal muscle injury using plasma fatty acid binding protein.

OBJECTIVE: To test whether fatty acid binding protein (FABP) is a useful plasma marker for the early detection of exercise induced skeletal muscle injury in healthy subjects. METHODS: Plasma concentrations...

Elevated muscle vitamin E does not attenuate eccentric exercise-induced muscle injury.

The purpose of this study was to evaluate the effect of elevated muscle vitamin E content on skeletal muscle damage from eccentric exercise. Sixty Sprague-Dawley rats were put on a normal (40 IU vitamin E/kg food) or supplemented (10,000 IU vitamin E/kg food) diet for 5 wk. Injury in soleus muscle was determined using several criteria: reductions in maximal tetanic force and number of intact fibers per square millimeter and elevations in muscle glucose 6-phosphate dehydrogenase activity and plasma creatine kinase activity, either immediately (0 h) or 2 days (48 h) after a downhill walking protocol. Sedentary animals were also tested but did not exercise. Muscle vitamin E levels were significantly elevated (approximately 3- to 4-fold), and susceptibility of the muscles to oxidant stress was decreased, after supplementation. However, vitamin E supplementation did not attenuate injury by any of the criteria employed. Maximal tetanic force decreased approximately 20% at 0 and 48 h after exercise in both groups. The number of intact fibers per square millimeter decreased approximately 30-35% in both groups at 0 and 48 h. Glucose 6-phosphate dehydrogenase activity increased approximately 50-100% in both groups at 48 h, and plasma creatine kinase activity was elevated approximately 2- to 2.5-fold at 0 h in both groups. These findings do not support a major role for free radical damage to muscle membranes in the initiation of injury from eccentric exercise, although they do not disprove free radical involvement in the etiology.