Blood Leukocyte mRNA Expression for IL-10, IL-1Ra, and IL-8, but Not IL-6, Increases After Exercise

The primary purpose of this project was to study exercise-induced leukocyte cytokine mRNA expression. Changes in plasma cytokine levels and blood leukocyte mRNA expression for interleukin-6 (IL-6), IL-8, IL- 10, and IL-1 receptor antagonist (IL-1Ra) were measured in 12 athletes following 2 h of intensive cycling (64% Wattsmax) while ingesting a carbohydrate or placebo beverage (randomized and double blinded). Blood samples were collected 30 min preexercise and immediately and 1 h postexercise. Carbohydate compared with placebo ingestion attenuated exercise-induced changes in plasma cortisol (8.8% vs. 62%, respectively), epinephrine (–9.2% vs. 138%), IL-6 (10-fold vs. 40-fold), IL-10 (8.9-fold vs. 26-fold, and IL-1Ra (2.1-fold vs. 5.6-fold). Significant time effects were measured for blood leukocyte IL-8 (2.4-fold increase 1 h postexercise), IL-10 (2.7-fold increase), IL-1Ra (2.2-fold increase), and IL-6 (0.8-fold decrease) mRNA content, with no significant differences between Cho and Pla test conditions. In summary, gene expression for IL-8, IL-10, and IL-1Ra, but not IL-6, is increased in blood leukocytes taken from athletes following 2 h of intensive cycling and is not influenced by carbohydrate compared with placebo ingestion. mRNA expression was high enough to indicate a substantial contribution of blood leukocytes to plasma levels of IL-8, IL-10, and IL-1Ra during prolonged exercise

Original Research Oral Quercetin Supplementation and Blood Oxidative Capacity in Response to Ultramarathon Competition

Previous research indicates that ultramarathon exercise can result in blood oxidative stress. The purpose of this investigation was to examine the efficacy of oral supplementation with quercetin, a naturally occurring compound with known antioxidant properties, as a potential countermeasure against blood oxidative stress during an ultramarathon competition. In double-blind fashion, 63 participants received either oral quercetin (250 mg, 4×/day; 1,000 mg/day total) or quercetin-free supplements 3 weeks before and during the 160-km Western States Endurance Run. Blood drawn before and immediately after (quercetin finishers n = 18, quercetin-free finishers n = 21) the event was analyzed for changes in blood redox status and oxidative damage. Results show that quercetin supplementation did not affect race performance. In response to the ultramarathon challenge, aqueous-phase antioxidant capacity (ferric-reducing ability of plasma) was similarly elevated in athletes in both quercetin and quercetin-free treatments and likely reflects significant increases in plasma urate levels. Alternatively, trolox-equivalent antioxidant capacity was not altered by exercise or quercetin. Accordingly, neither F2-isoprostances nor protein carbonyls were influenced by either exercise or quercetin supplementation. In the absence of postrace blood oxidative damage, these findings suggest that oral quercetin supplementation does not alter blood plasma lipid or aqueous-phase antioxidant capacity or oxidative damage during an ultramarathon challenge

Original Research Oral Quercetin Supplementation and Blood Oxidative Capacity in Response to Ultramarathon Competition

Previous research indicates that ultramarathon exercise can result in blood oxidative stress. The purpose of this investigation was to examine the efficacy of oral supplementation with quercetin, a naturally occurring compound with known antioxidant properties, as a potential countermeasure against blood oxidative stress during an ultramarathon competition. In double-blind fashion, 63 participants received either oral quercetin (250 mg, 4×/day; 1,000 mg/day total) or quercetin-free supplements 3 weeks before and during the 160-km Western States Endurance Run. Blood drawn before and immediately after (quercetin finishers n = 18, quercetin-free finishers n = 21) the event was analyzed for changes in blood redox status and oxidative damage. Results show that quercetin supplementation did not affect race performance. In response to the ultramarathon challenge, aqueous-phase antioxidant capacity (ferric-reducing ability of plasma) was similarly elevated in athletes in both quercetin and quercetin-free treatments and likely reflects significant increases in plasma urate levels. Alternatively, trolox-equivalent antioxidant capacity was not altered by exercise or quercetin. Accordingly, neither F2-isoprostances nor protein carbonyls were influenced by either exercise or quercetin supplementation. In the absence of postrace blood oxidative damage, these findings suggest that oral quercetin supplementation does not alter blood plasma lipid or aqueous-phase antioxidant capacity or oxidative damage during an ultramarathon challenge

Editorial Redox Biology of Exercise

Redox biology is probably the most rapidly expanding field in biology. Indeed, the number of conferences, journals, and books devoted to redox biology is increasing and it is very often seen that major biology journals publish special issues on this area (e.g., Exercise is perhaps one of the most characteristic examples demonstrating that reactive species are not necessarily "harmful" entities, considering that the well-known benefits of regular exercise on muscle function and health are accompanied by repeated episodes of oxidative and nitrosative stress. In addition, an ongoing debate exists in the literature regarding the implications of antioxidant supplementation on physical performance and redox homeostasis. Considering that the redox biology of exercise is by nature multidisciplinary, this special issue is compiled of original and review articles combining chemical, analytical, biochemical, nutritional, physiological, and medical aspects relevant to reactive species biology. Reading through these papers the multiple facets of exercise redox biology are revealed. The review article by E. C. Gomes et al. presents the current state of knowledge on the redox biology of exercise. It provides a comprehensive perspective on the contribution of various intracellular and extracellular sources and the identity of oxidants produced by exercising animals and humans. It also focuses on the possible role of these exercise-induced oxidants in important training adaptations such as angiogenesis, mitochondria biogenesis, and muscle hypertrophy. This article lays the groundwork for the other articles of the special issue that address oxidant effects on exercise performance and redox homeostasis and diseases. Specifically, H. Pan et al. indicated that electrical stimulation of skeletal muscle cells increased the production of reactive species as well as the mRNA and protein levels of interleukin-6. The authors hypothesized that reactive species generation induced by skeletal muscle contraction may be one of the factors regulating musclederived interleukin-6 production and release. Using a more physiological relevant methodology, S. Mrakic-Sposta et al. employed an electron paramagnetic resonance technique for the rapid and noninvasive measurement of reactive species concentration directly in fresh human peripheral blood. Using this innovative approach, they reported that short-term high-intensity exercise increased reactive species production whereas the resting levels of reactive species decreased following supplementation with the antioxidant cofactor α-lipoic acid

Successive Bouts of Cycling Stimulates Genes Associated with Mitochondrial Biogenesis

Exercise increases mRNA for genes involved in mitochondrial biogenesis and oxidative enzyme capacity. However, little is known about how these genes respond to consecutive bouts of prolonged exercise. We examined the effects of 3 h of intensive cycling performed on three consecutive days on the mRNA associated with mitochondrial biogenesis in trained human subjects. Forty trained cyclists were tested for VO2max (54.7 ± 1.1 ml kg−1 min−1). The subjects cycled at 57% wattsmax for 3 h using their own bicycles on CompuTrainer™ Pro Model trainers (RacerMate, Seattle, WA) on three consecutive days. Muscle biopsies were obtained from the vastus lateralis pre- and post-exercise on days one and three. Muscle samples were analyzed for mRNA content of peroxisome proliferator receptor gamma coactivator-1 alpha (PGC-1α), sirtuin 1 (Sirt-1), cytochrome c, and citrate synthase. Data were analyzed using a 2 (time) × 2 (day) repeated measures ANOVA. Of the mRNA analyzed, the following increased from pre to post 3 h rides: cytochrome c (P = 0.006), citrate synthase (P = 0.03), PGC-1α (P \u3c 0.001), and Sirt-1 (P = 0.005). The following mRNA showed significant effects from days one to three: cytochrome c (P \u3c 0.001) and citrate synthase (P = 0.01). These data show that exhaustive cycling performed on three consecutive days resulted in both acute and chronic stimuli for mRNA associated with mitochondrial biogenesis in already trained subjects. This is the first study to illustrate an increase in sirtuin-1 mRNA with acute and chronic exercise. These data contribute to the understanding of mRNA expression during both acute and successive bouts of prolonged exercise

Quercetin Ingestion Does Not Alter Cytokine Changes in Athletes Competing in the Western States Endurance Run

The purpose of this study was to measure the influence of quercetin on plasma cytokines, leukocyte cytokine mRNA, and related variables in ultramarathoners competing in the 160-km Western States Endurance Run (WSER). Sixty-three runners were randomized to quercetin and placebo groups and under double-blinded methods ingested 1000 mg/day quercetin for 3 weeks before the WSER. Thirty-nine of the 63 subjects (n = 18 for quercetin, n = 21 for placebo) finished the race and provided blood samples the morning before the race and 15–30 min postrace. Significant prerace to postrace WSER increases were measured for nine proinflammatory and anti-inflammatory plasma cytokines, cortisol (quercetin = 94%, placebo = 96%), serum C-reactive protein (CRP) (mean ± SE absolute increase, quercetin = 31.8 ± 4.2, placebo = 38.2 ± 5.0 mg/L), and creatine kinase (CK) (quercetin = 21,575 ± 3,977, placebo = 19,455 ± 3,969 U/L), with no significant group differences. Interleukin-6 (IL-6) mRNA did not change post-WSER, with a significant decrease measured for leukocyte IL-8 mRNA (0.21 ± 0.03-fold and 0.25 ± 0.04-fold change from rest, quercetin and placebo, respectively) and significant increases for IL-1Ra mRNA (1.43 ± 0.18-fold and 1.40 ± 0.16-fold change, quercetin and placebo, respectively) and IL-10 mRNA (12.9 ± 3.9-fold and 17.2 ± 6.1-fold change, quercetin and placebo, respectively), with no significant differences between groups. In conclusion, quercetin ingestion (1 g/day) by ultramarathon athletes for 3 weeks before a competitive 160-km race significantly increased plasma quercetin levels but failed to attenuate muscle damage, inflammation, increases in plasma cytokine and hormone levels, and alterations in leukocyte cytokine mRNA expression

Muscle damage is linked to cytokine changes following a 160-km race

Abstract Muscle damage and perceived soreness following the 160-km Western States Endurance Run were related to changes in plasma cytokines and use of nonsteroidal anti-inXammatory drugs (NSAIDS). Subjects included 60 ultramarathoners (mean § SE, age 45.3 § 1.1 years) who Wnished the race in under 30 h (26.3 § 0.4 h). Blood samples were collected the morning prior to and immediately following the race, and subjects recorded muscle soreness during the week following the race using a 10-point Likert scale (DOMS). Seven plasma cytokines were measured including IL-6, IL-10, IL-8, IL-1ra, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein 1 (MCP-1), and macrophage inXammatory protein 1 (MIP-1 ). Cytokine changes were compared between NSAID users and nonusers, and correlated with creatine phosphokinase (CPK) and DOMS. SigniWcant increases were measured for all seven cytokines, with the greatest fold increases seen for IL-6 (125£), IL-10 (24£), and G-CSF (12£). CPK was correlated with changes in IL-6, G-CSF, IL-10, IL-1ra, and MCP-1 (r D .49-.68), (P < .001), but not IL-8 or MIP-1 . DOMS averaged 7.1 § 0.3 the day after the race, and 5.0 § 0.3, 2.5 § 0.2, and 1.6 § 0.1 3 days, 5 days, and 7 days post-race, respectively, and each was correlated with CPK (r D .40-.63, P < .001) and changes in IL-6, G-CSF, IL-10, and MCP-1 (r D .28-.77, P < .05). A comparison of NSAID users (72% of athletes) and nonusers showed no diVerences in CPK or DOMS, but did reveal greater increases in Wve of seven cytokines in the NSAID users (P < .05). In conclusion, muscle damage in athletes competing in a 160-km race was signiWcantly correlated with post-race DOMS and increases in Wve of seven cytokines. NSAID users did not experience a reduction in muscle damage or DOMS, but did have higher post-race plasma levels in Wve of seven cytokines

Effect of Resveratrol and Quercetin Supplementation On Redox Status and Inflammation After Exercise

Resveratrol and quercetin function as antioxidants and anti-inflammatories in vitro, but these mechanisms have been minimally examined in combination in exercising humans. The purpose of this investigation was to examine supplementation as a countermeasure against oxidative stress and inflammation in response to exercise. Fourteen athletes were randomly assigned, in a double-blind crossover design, to a resveratrol and quercetin combination (RQ) (120 mg resveratrol and 225 mg quercetin for 6 days and 240 mg resveratrol and 450 mg quercetin on day 7 just prior to exercise) or to placebo (P). There was a 1-week washout between trials. Blood was taken at baseline, pre-exercise, immediately after exercise, and 1 h after exercise. Plasma was analyzed for oxidative stress (F2-isoprostanes and protein carbonyls), antioxidant capacity (ferric-reducing ability of plasma (FRAP), Trolox equivalent antioxidant capacity (TEAC), oxygen radical absorptive capacity (ORAC)), and inflammation (cytokine interleukin (IL)-8 and C-reactive protein (CRP)). Statistical design utilizeda2×3ANOVA and Student\u27s t test. Pre-exercise values were not different from baseline for any measure. The postexercise increase in F2-isoprostanes was significantly less (p = 0.039 interaction) with RQ (68%) than with P (137%). Protein carbonyls, FRAP, ORAC, and TEAC significantly increased after exercise but were not affected by treatment. IL-8 and CRP increased significantly immediately after exercise but were not affected by treatment. These data indicate that RQ significantly reduces exercise-induced lipid peroxidation without associated changes in inflammation or plasma antioxidant status