Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage

Downhill running is associated with fiber damage, inflammation, delayed-onset muscle soreness, and various functional deficits. Curcumin, a constituent of the Indian spice turmeric has been investigated for its anti-inflammatory activity and may offset some of the damage and functional deficits associated with downhill running. This study examined the effects of curcumin on inflammation and recovery of running performance following downhill running in mice. Male mice were assigned to downhill placebo (Down-Plac), downhill curcumin (Down-Cur), uphill placebo (Up-Plac), or uphill curcumin (Up-Cur) groups and run on a treadmill at 22 m/min at -14% or +14% grade, for 150 min. At 48 h or 72 h after the up/downhill run, mice (experiment 1) underwent a treadmill performance run to fatigue. Another subset of mice was placed in voluntary activity wheel cages following the up/downhill run (experiment 2) and their voluntary activity (distance, time and peak speed) was recorded. Additional mice (experiment 3) were killed at 24 h and 48 h following the up/downhill run, and the soleus muscle was harvested for analysis of inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), and plasma was collected for creatine kinase analysis. Downhill running decreased both treadmill run time to fatigue (48 h and 72 h) and voluntary activity (24 h) (P < 0.05), and curcumin feedings offset these effects on running performance. Downhill running was also associated with an increase in inflammatory cytokines (24 h and 48 h) and creatine kinase (24 h) (P < 0.05) that were blunted by curcumin feedings. These results support the hypothesis that curcumin can reduce inflammation and offset some of the performance deficits associated with eccentric exercise-induced muscle damage.     

Walking kinematics and kinetics following eccentric exercise-induced muscle damage

The goal of this investigation was to investigate how walking patterns are affected following muscle-damaging exercise by quantifying both lower limb kinematics and kinetics. Fifteen young women conducted a maximal isokinetic eccentric exercise (EE) muscle damage protocol (5 × 15) of the knee extensors and flexors of both legs at 60°/s. Three-dimensional motion data and ground reaction forces (GRFs) were collected 24 h pre-EE while the participants walked at their preferred self-selected walking speed (SWS). Participants were asked to perform two gait conditions 48 h post-EE. The first condition (COND1) was to walk at their own speed and the second condition (COND2) to maintain the SWS (±5%) they had 24 h pre-EE. Walking speed during COND1 was significantly lower compared to pre-exercise values. When walking speed was controlled during COND2, significant effects of muscle damage were noticed, among other variables, for stride frequency, loading rate, lateral and vertical GRFs, as well as for specific knee kinematics and kinetics. These findings provide new insights into how walking patterns are adapted to compensate for the impaired function of the knee musculature following muscle damage. The importance to distinguish the findings caused by muscle damage from those exhibited in response to changes in stride frequency is highlighted.     

Temperature dependency of force loss and Ca(2+) homeostasis in mouse EDL muscle after eccentric contractions

The goals of this study were first to determine the effect of temperature on the force loss that results from eccentric contractions in mouse extensor digitorum longus (EDL) muscles and then to evaluate a potential role for altered Ca(2+) homeostasis explaining the greater isometric force loss observed at the higher temperatures. Isolated muscles performed five eccentric or five isometric contractions at either 15, 20, 25, 30, 33.5, or 37 degrees C. Isometric force loss, caffeine-induced force, lactate dehydrogenase (LDH) release, muscle accumulation of (45)Ca(2+) from the bathing medium, sarcoplasmic reticulum (SR) Ca(2+) uptake, and resting muscle fiber free cytosolic Ca(2+) concentration ([Ca(2+)](i)) were measured. The isometric force loss after eccentric contractions increased progressively as temperature rose; at 15 degrees C, there was no significant loss of force, but at 37 degrees C, there was a 30-39% loss of force. After eccentric contractions, caffeine-induced force was not affected by temperature nor was it different from that of control muscles at any temperature. Loss of cell membrane integrity and subsequent influx of extracellular Ca(2+) as indicated by LDH release and muscle (45)Ca(2+) accumulation, respectively, were minimal over the 15-25 degrees C range, but both increased as an exponential function of temperature between 30 and 37 degrees C. SR Ca(2+) uptake showed no impairment as temperature increased, and the eccentric contraction-induced rise in resting fiber [Ca(2+)](i) was unaffected by temperature over the 15-25 degrees C range. In conclusion, the isometric force loss after eccentric contractions is temperature dependent, but the temperature dependency does not appear to be readily explainable by alterations in Ca(2+) homeostasis.     

Effects of a protease supplement on eccentric exercise-induced markers of delayed-onset muscle soreness and muscle damage

This investigation examined the effects of a protease supplement on selected markers of muscle damage and delayed-onset muscle soreness (DOMS). The study used a double-blinded, placebo-controlled, crossover design. Twenty men (mean +/- SD age = 21.0 +/- 3.1 years) were randomly assigned to either a supplement group (SUPP) or a placebo group (PLAC). All subjects were tested for unilateral isometric forearm flexion strength, hanging joint angle, relaxed arm circumference, subjective pain rating, and plasma creatine kinase activity and myoglobin concentration. The testing occurred before (TIME1), immediately after (TIME2), and 24 (TIME3), 48 (TIME4), and 72 (TIME5) hours after a bout of eccentric exercise. During these tests, the subjects in the SUPP group ingested a protease supplement. The subjects in the PLAC group took microcrystalline cellulose. After testing at TIME5 and 2 weeks of rest, the subjects were crossed over into the opposite group and performed the same tests as during visits 1-5, but with the opposite limb. Overall, isometric forearm flexion strength was greater (7.6%) for the SUPP group than for the PLAC group, despite nearly identical (difference = 0.14 N.m, p = 0.940) mean strength values before (TIME1) the eccentric exercise protocol. There were no between-group differences for hanging joint angle, relaxed arm circumference, subjective pain ratings, and plasma creatine kinase activity and myoglobin concentration from TIME1 to TIME5. These findings provided initial evidence that the protease supplement may be useful for reducing strength loss immediately after eccentric exercise and for aiding in short-term strength recovery. The protease supplement had no effect, however, on the perception of pain associated with DOMS or the blood markers of muscle damage.     

Assessment of eccentric exercise-induced muscle damage of the elbow flexors by tensiomyography

Exercise induced muscle damage (EIMD) impairs maximal torque production which can cause a decline in athletic performance and/or mobility. EIMD is commonly assessed by using maximal voluntary contraction (MVC), creatine kinase (CK) and muscle soreness. We propose as an additional technique, tensiomyography (TMG), recently introduced to measure mechanical and muscle contractile characteristics. The purpose of this study was to determine the validity of TMG in detecting changes in maximal torque following EIMD. Nineteen participants performed eccentric elbow flexions to achieve EIMD on the non- dominant arm and used the dominant elbow flexor as a control. TMG parameters, MVC and rate of torque development (RTD) were measured prior to EIMD and repeated for another six consecutive days. Creatine kinase, muscle soreness and limb girth were also measured during this period. Twenty four hours after inducing EIMD, MVC torque, RTD and TMG maximal displacement had significantly (p<0.01) declined by 37%, 44% and 31%, respectively. By day 6 MVC, RTD and TMG recovered to 12%, 24% and 17% of respective pre-EIMD values. In conclusion, as hypothesised TMG maximal displacement significantly followed other standard EIMD responses. This could therefore be useful in detecting muscle damage from impaired muscle function and its recovery following EIMD.     

Time course of muscle adaptation after high force eccentric exercise

The repeated bout effect on changes in muscle damage indicators was examined in two groups of subjects following two bouts of 70 maximal eccentric actions of the forearm flexors. Fourteen college age female subjects were placed into two groups. The two bouts were separated by 6 weeks (n = 6), and 10 weeks (n = 8). The subjects performed the same amount of work for the bouts. The muscle damage indicators were isometric strength (STR), relaxed elbow joint angle (RANG), flexed elbow joint angle (FANG), perceived muscle soreness ratings (SOR), and plasma creatine kinase activity (CK). These measures were obtained pre-exercise and 5 days following each bout. The first bout showed significant changes in all measures over time for both groups (P less than 0.01). For the 6-week group, significantly smaller changes in RANG (P less than 0.01), SOR (P less than 0.05), and CK (P less than 0.01), as well as significantly faster recoveries (P less than 0.05) for STR and FANG were produced in the second bout. For the 10-week group, significantly smaller changes in RANG (P less than 0.05) and CK (P less than 0.01) were demonstrated by the second bout, but not significant difference was found for STR, FANG, and SOR between bouts 1 and 2. Changes in CK were still significantly smaller than that of the first bout when 6 subjects (3 subjects from each group) performed the same exercise 6 months after the second bout, but no difference in other measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Mechanisms of aging in senescence-accelerated mice

Background  

Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J).     

Analysis of spermatogenesis in senescence-accelerated mice

A comparative analysis of age-related dynamics of spermatogenesis has been performed in mutant mouse lines predisposed or resistant to accelerated senescence (SAMP1 and SAMR1 respectively). The results show that quantitative and morphohistological trends in the development of sperm cells and Sertoli cells in both lines are similar in both lines. Their comparison with data obtained in our previous studies (Zakhidov et al., 2001; Gordeeva et al., 2001) shows that sharp quantitative and qualitative changes in the structure of the spermatogenic system have occurred in senescence-accelerated mice of new generations, which confirms the fact of dynamic instability of the germinal lineage. The role of stem spermatogonial cells in restoration of spermatogenesis in animals reaching the critical age is discussed.     

Different types of tea products attenuate inflammation induced in Trypanosoma brucei infected mice

An in vivo study was carried out to determine the effect of different types of Kenyan tea extracts on male Swiss albino mice infected with Trypanosoma brucei brucei isolate KETRI 2710. The isolate produced a similar clinical picture after a pre-patent period of 5 days post-infection (DPI). Parasitemia levels in the untreated mice and those given different teas developed exponentially at similar rates reaching similar densities at the peak of parasitemia 8 DPI. Between 9 and 13 DPI parasitemia decreased more rapidly in tea treated compared to the untreated mice which indicated that tea lowered parasitemia level. Anaemia indicated by a fall in erythrocyte packed cell volume (PCV) occurred within 4 DPI and remained below the normal levels until the terminal stages of the disease. A significant difference (P<0.05) was observed 11 DPI between the tea treated and the untreated mice indicating that tea enhanced resistance to erythrocyte destruction. Mice treated with tea exhibited significantly (P<0.01) reduced parasite-induced hypoalbuminemia as compared to the untreated. Since albumin is a negative acute phase protein, it shows a decrease during inflammatory conditions and therefore its elevation in the mice given tea in this study clearly demonstrated that tea ameliorated inflammation induced by T. b. brucei. Although green and white teas were superior in most of these characteristics, black tea, which is the principle tea product from Kenya, displayed remarkable properties some even comparable to those of green tea. Interestingly, tea was more efficacious than dexamethasone an established anti-inflammatory drug, demonstrating its therapeutic potential.     

Mitochondrial dysfunction in platelets and hippocampi of senescence-accelerated mice

Senescence-accelerated mice (SAM) strains are useful models to understand the mechanisms of age-dependent degeneration. In this study, measurements of the mitochondrial membrane potential (Δψ_m) of platelets and the Adenosine 5^′-triphosphate (ATP) content of hippocampi and platelets were made, and platelet mitochondria were observed in SAMP8 (faster aging mice) and SAMR1 (aging resistant control mice) at 2, 6 and 9 months of age. In addition, an Aβ-induced (Amyloid beta-protein) damage model of platelets was established. After the addition of Aβ, the Δψ_m of platelets of SAMP8 at 1and 6 months of age were measured. We found that platelet Δψ_m, and hippocampal and platelet ATP content of SAMP8 mice decreased at a relatively early age compared with SAMR1. The platelets of 6 month-old SAMP8 showed a tolerance to Aβ-induced damages. These results suggest that mitochondrial dysfunction might be one of the mechanisms leading to age-associated degeneration in SAMP mice at an early age and the platelets could serve as a biomarker for detection of mitochondrial function and age related disease.     

Reduced susceptibility to eccentric exercise-induced muscle damage in resistance-trained men is not linked to resistance training-related neural adaptations

The purpose of this study was to examine the acute effects of maximal concentric vs. eccentric exercise on the isometric strength of the elbow flexor, as well as the biceps brachii muscle electromyographic (EMG) responses in resistance-trained (RT) vs. untrained (UT) men. Thirteen RT men (age: 24 ± 4 years; height: 180.2 ± 7.7 cm; body weight: 92.2 ± 16.9 kg) and twelve UT men (age: 23 ± 4 years; height: 179.2 ± 5.0 cm; body weight: 81.5 ± 8.6 kg) performed six sets of ten maximal concentric isokinetic (CON) or eccentric isokinetic (ECC) elbow flexion exercise in two separate visits. Before and after the exercise interventions, maximal voluntary contractions (MVCs) were performed for testing isometric strength. In addition, bipolar surface EMG signals were detected from the biceps brachii muscle during the strength testing. Both CON and ECC caused isometric strength to decrease, regardless of the training status. However, ECC caused greater isometric strength decline than CON did for the UT group (p = 0.006), but not for the RT group. Both EMG amplitude and mean frequency significantly decreased and increased, respectively, regardless of the training status and exercise intervention. Resistance-trained men are less susceptible to eccentric exercise-induced muscle damage, but this advantage is not likely linked to the chronic resistance training-induced neural adaptations.     

The multiple roles of titin in muscle contraction and force production

Titin is a filamentous protein spanning the half-sarcomere, with spring-like properties in the I-band region. Various structural, signaling, and mechanical functions have been associated with titin, but not all of these are fully elucidated and accepted in the scientific community. Here, I discuss the primary mechanical functions of titin, including its accepted role in passive force production, stabilization of half-sarcomeres and sarcomeres, and its controversial contribution to residual force enhancement, passive force enhancement, energetics, and work production in shortening muscle. Finally, I provide evidence that titin is a molecular spring whose stiffness changes with muscle activation and actin–myosin-based force production, suggesting a novel model of force production that, aside from actin and myosin, includes titin as a “third contractile” filament. Using this three-filament model of sarcomeres, the stability of (half-) sarcomeres, passive force enhancement, residual force enhancement, and the decrease in metabolic energy during and following eccentric contractions can be explained readily.     

Ganoderma lucidum polysaccharides supplementation attenuates exercise-induced oxidative stress in skeletal muscle of mice

The present study was designed to determine the effects of Ganoderma lucidum polysaccharides (GL-PS) on exhaustive exercise-induced oxidative stress in skeletal muscle tissues of mice. The mice were divided into four groups (three GL-PS administered groups and the control group). The control group was administered with distilled water and GL-PS administered groups were administered with GL-PS (50, 100 and 200 mg/kg body weight per day). After 28 days, the mice performed an exhaustive swimming exercise, along with the determination of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) activities and malondialdehyde (MDA) levels in the skeletal muscle of mice. The results showed that GL-PS could increase antioxidant enzymes activities and decrease the MDA levels in the skeletal muscle of mice. This study provides strong evidence that GL-PS supplementation possessed protective effects against exhaustive exercise-induced oxidative stress.     

Experimental knee pain impairs submaximal force steadiness in isometric,eccentric, and concentric muscle actions

IntroductionPopulations with knee joint damage, including arthritis, have noted impairments in the regulation of submaximal muscle force. It is difficult to determine the exact cause of such impairments given the joint pathology and associated neuromuscular adaptations. Experimental pain models that have been used to isolate the effects of pain on muscle force regulation have shown impaired force steadiness during acute pain. However, few studies have examined force regulation during dynamic contractions, and these findings have been inconsistent. The goal of the current study was to examine the effect of experimental knee joint pain on submaximal quadriceps force regulation during isometric and dynamic contractions.MethodsThe study involved fifteen healthy participants. Participants were seated in an isokinetic dynamometer. Knee extensor force matching tasks were completed in isometric, eccentric, and concentric muscle contraction conditions. The target force was set to 10 % of maximum for each contraction type. Hypertonic saline was then injected into the infrapatella fat pad to generate acute joint pain. The force matching tasks were repeated during pain and once more 5 min after pain had subsided.ResultsHypertonic saline resulted in knee pain with an average peak pain rating of 5.5 ± 2.1 (0–10 scale) that lasted for 18 ± 4 mins. Force steadiness significantly reduced during pain across all three muscle contraction conditions. There was a trend to increased force matching error during pain but this was not significant.ConclusionExperimental knee pain leads to impaired quadriceps force steadiness during isometric, eccentric, and concentric contractions, providing further evidence that joint pain directly affects motor performance. Given the established relationship between submaximal muscle force steadiness and function, such an effect may be detrimental to the performance of tasks in daily life. In order to restore motor performance in people with painful arthritic conditions of the knee, it may be important to first manage their pain more effectively.     

Altered muscle force and stiffness of skeletal muscles in alpha-sarcoglycan-deficient mice

Alpha-sarcoglycan (ASG) is a transmembrane protein of the dystrophin-associated complex, and absence of ASG causes limb-girdle muscular dystrophy. We hypothesize that disruption of the sarcoglycan complex may alter muscle extensibility and disrupt the coupling between passive transverse and axial contractile elements in the diaphragm. We determined the length-tension relationships of the diaphragm of young ASG-deficient mice and their controls during uniaxial and biaxial loading. We also determined the isometric contractile properties of the diaphragm muscles from mutant and normal mice in the absence and presence of passive transverse stress. We found that the diaphragm muscles of the null mutants for the protein ASG show 1) significant decrease in muscle extensibility in the directions of the muscle fibers and transverse to fibers, 2) significant reductions in force-generating capacity, and 3) significant reductions in coupling between longitudinal and transverse properties. Thus these findings suggest that the sarcoglycan complex serves a mechanical function in the diaphragm by contributing to muscle passive stiffness and to the modulation of the contractile properties of the muscle.     

Muscular hypertrophy and changes in cytokine production after eccentric training in the rat skeletal muscle

We investigated the time course effects of eccentric training on muscular size, strength, and growth factor/cytokine production by using an isokinetic-exercise system for rats. Male Wistar rats (n = 34) were randomly assigned into 4 groups: 5 session eccentric-training group (ECC5S, n = 10); 5 session sham-operated group (CON5S, n = 10); 10 session eccentric-training group (ECC10S, n = 7); 10 session sham-operated group (CON10S, n = 7). In each group, a session of either training or sham operation was performed every 2 days. The training consisted of 4 sets of forced dorsiflexion (5 repetitions) combined with electric stimulation of plantar flexors. The wet weight of medial gastrocnemius muscle did not increase significantly after 5 sessions of training, whereas that after 10 sessions of training significantly increased with a concomitant increase in the cross-sectional area (CSA) of muscle fibers (weight, p < 0.05; fiber CSA, p < 0.001). Interleukin (IL)-6 in ECC5S and ECC10S groups showed significant increases (p < 0.01), whereas those of tumor necrosis factor (TNF)-α and IL-10 did not. The phospho-stat-3 showed a significant increase in ECC10S (p < 0.001) but not in ECC5S. Myostatin and follistatin also showed significant differences only between ECC10S and CON10S (p < 0.05). The results showed that repeated sessions of eccentric training for 20 days cause increases in muscular size and strength associated with increases in IL-6, follistatin, phospho-stat-3, and a decrease in myostatin. The delayed responses of IL-6, myostatin, phospho-stat-3, and follistatin would be due to the chronic effects of repeated training and possibly important for muscular hypertrophy.     

Acceleration of chromosome aberrations in senescence-accelerated strains of mice

Age-related changes in the frequency of chromosome aberrations were examined using bone marrow cells of senescence-accelerated strains of mice (SAM). An accelerated senescence-prone strain, SAM-P/1, showed a striking increase in the frequency of chromosome aberrations, from age 3 to 8 months, whereas an accelerated senescence-resistant strain, SAM-R/1, at the same ages showed only a slight increase. Both these strains were derived from the same ancestral strain (AKR/J). The rate of increase of chromosome aberration frequency paralleled the advancement of senescence in both strains. These observations suggest that there are genetic factors which closely relate to chromosomal instability and acceleration of the senescence processes.