Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation

Characterization of the <i>Sideritis scardica</i> Extract SidTea+^TM and Its Effect on Physiological Profile, Metabolic Health and Redox Biomarkers in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study

This study aimed to characterize a Sideritis scardica extract (SidTea+TM) and investigate its effect on the physiological profile, metabolic health and redox status in healthy individuals. The chemical profile and antioxidant potential of the SidTea+TM extract were evaluated by UPLC-HRMS analysis and in vitro cell-free methods. Twenty-eight healthy adults participated in this randomized, double-blind, placebo-controlled study. Participants consumed 1500 mg/day of SidTea+TM or a placebo for 4 weeks. At baseline and post-supplementation, participants were assessed for their anthropometric and physiological profile and provided a resting blood sample. SidTea+TM decreased (p p TM also resulted in an increase (p 2max (+1.1 mL/kg/min) and a reduction (p TM increased (p p TM is a potent and safe to use antioxidant that can elicit positive changes in indices of blood pressure, cardiorespiratory capacity, liver metabolism, and redox status in healthy adults over a 4-week supplementation period

Antioxidation improves in puberty in normal weight and obese boys, in positive association with exercise-stimulated growth hormone secretion

BACKGROUND: Oxidative stress is associated with obesity while the evidence for the role of GH in pro- and antioxidation is inconclusive. This study investigates the relationships between growth hormone (GH), pro- and antioxidation in relation to obesity and puberty before and after an acute bout of exercise. METHODS: In this case control study, 76 healthy normal-weight and obese, prepubertal and pubertal boys underwent a blood sampling before and immediately after an aerobic exercise bout until exhaustion at 70% maximal oxygen consumption. Markers of prooxidation (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PCs)) and antioxidation (glutathione (GSH), oxidized glutathione disulfide (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPX), catalase, and total antioxidant capacity (TAC)) and hormones (GH, insulin-like growth factor (IGF)-1, IGF-BP-3, luteinizing hormone, follicle-stimulating hormone, and testosterone) were measured. RESULTS: Baseline and postexercise TBARS and PCs were greater, while baseline GSH, GSH/GSSG ratio, GPX, and TAC were lower in obese than that in normal-weight participants. In all participants, waist was the best negative and positive predictor for postexercise GPX and TBARS, respectively. Baseline TAC was greater in pubertal than that in pre-pubertal participants. In all participants, baseline GH was the best negative predictor for postexercise PCs. Significant positive linear correlation exists between the exercise-associated GH, and GSSG increases in pubertal normal-weight boys. CONCLUSIONS: Higher prooxidation and lower antioxidation were observed in obese boys, while antioxidation improves with puberty and postexercise, paralleling GH accentuated secretion

Regulation of Granulocyte Colony-Stimulating Factor and Its Receptor in Skeletal Muscle Is Dependent Upon the Type of Inflammatory Stimulus

The cytokine granulocyte colony-stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate hematopoietic stem cell mobilization, myelopoiesis, and the production and activation of neutrophils. In response to exercise-induced muscle damage, G-CSF is increased in circulation and G-CSFR has recently been identified in skeletal muscle cells. While G-CSF/G-CSFR activation mediates pro- and anti-inflammatory responses, our understanding of the role and regulation in the muscle is limited. The aim of this study was to investigate, in vitro and in vivo, the role and regulation of G-CSF and G-CSFR in skeletal muscle under conditions of muscle inflammation and damage. First, C2C12 myotubes were treated with lipopolysaccharide (LPS) with and without G-CSF to determine if G-CSF modulates the inflammatory response. Second, the regulation of G-CSF and its receptor was measured following eccentric exercise-induced muscle damage and the expression levels we investigated for redox sensitivity by administering the antioxidant N-acetylcysteine (NAC). LPS stimulation of C2C12 myotubes resulted in increases in G-CSF, interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF alpha) messenger RNA (mRNA) and an increase in G-CSF, IL-6, and MCP-1 release from C2C12 myotubes. The addition of G-CSF following LPS stimulation of C2C12 myotubes increased IL-6 mRNA and cytokine release into the media, however it did not affect MCP-1 or TNF alpha. Following eccentric exercise-induced muscle damage in humans, G-CSF levels were either marginally increased in circulation or remain unaltered in skeletal muscle. Similarly, G-CSFR levels remained unchanged in response to damaging exercise and G-CSF/G-CSFR did not change in response to NAC. Collectively, these findings suggest that G-CSF may cooperate with IL-6 and potentially promote muscle regeneration in vitro, whereas in vivo aseptic inflammation induced by exercise did not change G-CSF and G-CSFR responses. These observations suggest that different models of inflammation produce a different G-CSF response