BackgroundDoxorubicin, a widely used anti‐tumour drug, is known to cause muscle loss in cancer patients.MethodsFollowing an acute dose of doxorubicin injection (2.5 mg/kg per body weight), we examined macrophage distribution in rat soleus muscle challenged by eccentric exercise (downhill running). Long‐term doxorubicin treatment (one injection every 3 days) on muscle mass and survival were also determined.ResultsUnder non‐exercised condition, increased tumour necrosis factor (TNF)‐alpha mRNA and decreased IL‐10 mRNA were observed in soleus muscle of doxorubicin‐treated rats, compared with saline‐treated control rats. However, increases in inflammation score (leukocyte infiltration), nitrotyrosine level, and M1 macrophage (CD68+) invasion in exercised soleus muscle were absent in doxorubicin‐treated rats, whereas increased M2 macrophage (CD163+) localization in exercised muscle was less affected by doxorubicin. Despites coenzyme Q (Q10) supplementation significantly elevated TNF‐alpha mRNA, nitrotyrosine, and anti‐oxidant gamma‐glutamylcysteine synthetase (GCS) levels in non‐exercised soleus muscle, these pro‐inflammatory responses were also abolished in doxorubicin‐treated rats. Results from long‐term doxorubicin treatment show a significant muscle loss followed by an accelerated death, which cannot be reversed by Q10 supplementation.Conclusions(i) Doxorubicin impairs inflammation mechanism by depleting M1 macrophage in exercised skeletal muscle; (ii) Muscle loss and accelerated death during prolonged doxorubicin treatment cannot be reversed by Q10 supplementation.
BackgroundGinsenoside Rg1 has been shown to clear senescence-associated beta-galactosidase (SA-β-gal) in cultured cells. It remains unknown whether Rg1 can influence SA-β-gal in exercising human skeletal muscle.MethodsTo examine SA-β-gal change, 12 young men (age 21 ± 0.2 years) were enrolled in a randomized double-blind placebo controlled crossover study, under two occasions: placebo (PLA) and Rg1 (5 mg) supplementations 1 h prior to a high-intensity cycling (70% VO2max). Muscle samples were collected by multiple biopsies before and after cycling exercise (0 h and 3 h). To avoid potential effect of muscle biopsy on performance assessment, cycling time to exhaustion test (80% VO2max) was conducted on another 12 participants (age 23 ± 0.5 years) with the same experimental design.ResultsNo changes of SA-β-gal were observed after cycling in the PLA trial. On the contrary, nine of the 12 participants showed complete elimination of SA-β-gal in exercised muscle after cycling in the Rg1 trial (p < 0.05). Increases in apoptotic DNA fragmentation (PLA: +87% vs. Rg1: +133%, p < 0.05) and CD68+ (PLA: +78% vs. Rg1: +121%, p = 0.17) occurred immediately after cycling in both trials. During the 3-h recovery, reverses in apoptotic nuclei content (PLA: +5% vs. Rg1: −32%, p < 0.01) and increases in inducible nitrate oxide synthase and interleukin 6 mRNA levels of exercised muscle were observed only in the Rg1 trial (p < 0.01).ConclusionRg1 supplementation effectively eliminates senescent cells in exercising human skeletal muscle and improves high-intensity endurance performance.
Background: We have previously shown an accelerated recovery from muscle fatigue in men challenged by prolonged exercise after oral deep ocean minerals (DOM) supplementation. Here, we hypothesized a decrease in eccentric exercise-induced muscle inflammation in rats regularly consuming DOM-containing drinks (hardness 600 mg/L and fructose 11%).Methods: Forty-seven male Sprague Dawley rats were randomized into 4 groups: Control (C, N = 12), Fructose (F, N = 12), Fructose+Exercise (FE, N = 12), and Fructose+Exercise+DOM (FED, N = 11). Since fructose is a commonly used ingredient in beverages, 11% of fructose was added as a vehicle of the study. Soleus muscles of rats were analyzed 24 h after an acute bout of downhill running following 9 weeks of DOM supplementation.Results: Leukocyte infiltration and TNF-α mRNA of muscle in the FE group were 5 times and 4 times greater the F group, respectively, (P < 0.05). Both markers in the FED group were significantly lower than those in the FE group (P < 0.05). IL-10 mRNA of muscle in the F group was >eight fold greater than the C group (P < 0.05). The reduced glutathione (GSH) of muscle in the F group was 34% lower than that in the C group (P < 0.05). However, GSH levels were similar for the C and FED groups.Conclusion: Prolonged fructose supplementation modulates inflammatory balance of rat skeletal muscle. The results of the study suggest that DOM can minimize eccentric exercise-induced inflammatory cytokine responses in rat skeletal muscle.
Aerobic exercise induces oxidative stress and DNA damage, nevertheless, lowers cancer incidence. It remains unclear how genetic stability is maintained under this condition. Here, we examined the dynamic change of the tumor suppressor p16 INK4a in cells of skeletal muscle among young men following 60-min of aerobic cycling at 70% maximal oxygen consumption (V̇O 2max ). Rg1 (5 mg, an immunostimulant ginsenoside) and placebo (PLA) were supplemented 1 h before exercise. Data from serial muscle biopsies shows unchanged p16 INK4a+ cells after exercise followed by a considerable increase (+21-fold) in vastus lateralis muscle 3 h later. This increase was due to the accumulation of endothelial progenitor cells (p16 INK4a+ /CD34 + ) surrounding myofibers and other infiltrated nucleated cells (p16 INK4a+ /CD34 - ) in necrotic myofibers. During the Rg1 trial, acute increases of p16 INK4a+ cells in the muscle occurred immediately after exercise (+3-fold) and reversed near baseline 3 h later. Rg1 also lowered IL-10 mRNA relative to PLA 3 h after exercise. Post-exercise increases in VEGF mRNA and CD163 + macrophages were similar for PLA and Rg1 trials. Conclusion: The marked increases in p16 INK4a protein expression of endothelial progenitor cells in skeletal muscle implicates a protective mechanism for maintaining genetic stability against aerobic exercise. Rg1 accelerates resolution of the exercise-induced stress response.
Background: A series of racial specific predictive equations for exercise parameters are needed to determine a lack of cardiopulmonary fitness or having an exercise limitation on cardiopulmonary exercise testing (CPET). Objectives: The study aimed to develop a new set of predictive equations of CPET parameters during maximal cycling exercise for Thai adults. Methods: A sample of 580 Thai adults whom could pass screening tests were asked to fill a health questionnaire and the Global Physical Activity questionnaire. Participants with history of symptomatic heart and pulmonary diseases, current smokers, history of smoking ≥ 10 pack-years, and abnormal spirometry were excluded. The CPET was performed using a cycle ergometer with an incremental symptom-limited protocol. Values of CPET parameters at the peak exercise (oxygen uptake [V̇O2], work rate, heart rate, oxygen pulse, and minute ventilation), lactic acidosis threshold, and ventilatory equivalents for oxygen and carbon dioxide were documented. Analyses were stratified using age and gender criterion. Predictive equations for CPET parameters were established using multivariable linear regression with age (A), weight (W), height (H), and physical activity level (Act) as independent variables. Results: A total of 493 participants (208 men and 285 women) were analysed. The predictive equation of V̇O2peak (L.min-1) for males was: -2.268 + (0.037 × A) - (0.0005 × A2) + (0.016 × W) + (0.014 × H) + (0.104 × Act), (R2 = 0.41, SEE = 0.392), and for females, it was: -0.34 + (0.009 × A) - (0.0002 × A2) + (0.012 × W) + (0.005 × H) + (0.058 × Act), (R2 = 0.44, SEE = 0.220). Conclusions: This is the first study that constructed the predictive equations for cycling CPET parameters in Thai adults. These equations are useful to evaluate the cardiopulmonary health of the Thai population and may be generalized to other populations with geographical or ethnic proximity to the Thai people.
Naturally occurring tumor in animals receiving high minerals from deep oceans (DOM: hardness 600 mg/L) from 6 months of age until natural death was firstly assessed in 200 Sprague Dawley rats, randomized into four groups: Control (C), DOM (D), Fructose (F), and Fructose + DOM (FD). Fructose drink contained 11% fructose. Tumor incidence (necropsy at death) in the D group was ~40% lower than that in the C group (P < .05), together with lower body mass gain and greater locomotive activity during their initial 18 months (P < .05) but not during later life.X-ray image analysis on abnormal solid tissue among survivors at 18 and 24 months of age confirms a similar trend, exhibiting ~50% and ~65% lower tumor incidence than the C and F groups, respectively. Reduced-to-oxidized glutathione ratio (GSH/ GSSG) declined with age for the first three quarters of life on all groups (P < .05), followed by a resurgence during end-life among survivors at 24 months. This resurgence is markedly associated with lower tumor expansion but unrelated with DOM
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