title: Changes of thioredoxin, oxidative stress markers, inflammation and muscle/renal damage following intensive endurance exercise.
abstract: Thioredoxin (TRX) is a 12 kDa protein that is induced by oxidative stress, scavenges reactive oxygen species (ROS) and modulates chemotaxis. Furthermore it is thought to play a protective role in renal ischemia/reperfusion injury. Complement 5a (C5a) is a chemotactic factor of neutrophils and is produced after ischemia/reperfusion injury in the kidney. Both TRX and C5a increase after endurance exercise. Therefore, it may be possible that TRX has an association with C5a in renal disorders and/or renal protection caused by endurance exercise. Accordingly, the aim of this study was to investigate relationships among the changes of urine levels of TRX, C5a and acute kidney injury (AKI) caused by ischemia/reperfusion, inflammatory responses, and oxidative stress following intensive endurance exercise. Also, we applied a newly-developed measurement system of neutrophil migratory activity and ROS-production by use of ex vivo hydrogel methodology with an extracellular matrix to investigate the mechanisms of muscle damage. Fourteen male triathletes participated in a duathlon race consisting of 5 km of running, 40 km of cycling and 5 km of running were recruited to the study. Venous blood and urine samples were collected before, immediately following, 1.5 h and 3 h after the race. Plasma, serum and urine were analyzed using enzyme-linked immunosorbent assays, a free radical analytical system, and the ex vivo neutrophil functional measurement system. These data were analyzed by assigning participants to damaged and minor-damage groups by the presence and absence of renal tubular epithelial cells in the urinary sediments. We found strong associations among urinary TRX, C5a, interleukin (IL)-2, IL-4, IL-8, IL-10, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1. From the data it might be inferred that urinary TRX, MCP-1 and β-N-acetyl-D-glucosaminidase (NAG) were associated with renal tubular injury. Furthermore, TRX may be influenced by levels of IL-10, regulate chemotactic activity of C5a and IL-8, and control inflammatory progress by C5a and IL-8. In the longer duration group (minor-damage group), circulating neutrophil count, plasma concentration of myeloperoxidase (MPO) and serum concentration of myoglobin were markedly increased. In the higher intensity group (damaged group), neutrophil activation and degranulation of MPO might be inhibited, because not only was ROS production observed to be higher, but also antioxidant capacity and antiinflammatory cytokines were increased. Critically, the newlydeveloped ex vivo methodology corroborated the neutrophil activation levels in the two groups of participants.
authors.affiliation: Institute for Nanoscience & Nanotechnology, Waseda University, Tokyo, Japan.|Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugama
authors.affiliation: Faculty of Sport Sciences, Waseda University, Saitama, Japan.|Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology/ Waseda University, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Health Science Laboratory, Ezaki Glico Co., Ltd, Osaka, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Yoshitani
authors.affiliation: Health Science Laboratory, Ezaki Glico Co., Ltd, Osaka, Japan.
authors.forename: Koso
authors.initials: K
authors.lastname: Shiraishi
authors.affiliation: Mebiol Inc., Kanagawa, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miura
authors.affiliation: Mebiol Inc., Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshioka
authors.affiliation: Mebiol Inc., Kanagawa, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Food Science and Nutrition, Faculty of Agriculture, Kinki University, Nara, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kometani
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000652:urine; D000328:Adult; D056352:Athletes; D001642:Bicycling / Q000502:physiology; D015415:Biomarkers / Q000652:urine; D016207:Cytokines / Q000097:blood / Q000652:urine*; D015444:Exercise / Q000502:physiology*; D005081:Exercise Therapy; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000652:urine; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries*; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood; D010807:Physical Endurance / Q000502:physiology; D015427:Reperfusion Injury / Q000209:etiology / Q000652:urine; D012420:Running / Q000502:physiology; D013879:Thioredoxins / Q000652:urine*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D013879:Thioredoxins; D009195:Peroxidase
keywords: C5a; ROS; TRX; acute kidney injury (AKI).; anti-inflammation; antioxidant