title: Inflammatory Events and Oxidant Production in the Diaphragm, Gastrocnemius, and Blood of Rats Exposed to Chronic Intermittent Hypoxia: Therapeutic Strategies.
abstract: We hypothesized that inflammatory events and reactive oxygen species (ROS) production may be differentially expressed in respiratory and limb muscles, and blood of a chronic intermittent hypoxia (CIH) experimental model and that antioxidants and TNF-alpha blockade may influence those events. In blood, diaphragm, and gastrocnemius of rats non-invasively exposed to CIH (10% hypoxia, 2 h/day, 14 consecutive days) with/without concomitant treatment with either anti-TNF-alpha antibody (infliximab) or N-acetyl cysteine (NAC), inflammatory cytokines, superoxide anion production, muscle structural abnormalities, and fiber-type composition were assessed. Compared to non-exposed controls, in CIH-exposed rats, body weight gain was reduced, TNF-alpha, IL-1beta, IL-6, and interferon-gamma levels were increased in diaphragm, TNF-alpha, and IL-1 beta plasma levels were greater, systemic and muscle superoxide anion production was higher, diaphragm and gastrocnemius inflammatory cells and internal nuclei were higher, and muscle fiber-type and morphometry remained unmodified. CIH rats treated with infliximab further increased TNF-alpha, IL-1beta, IL-6, and interferon-gamma diaphragm levels, whereas NAC induced a reduction only in TNF-alpha and IL-1beta levels in diaphragm and plasma. Infliximab and NAC elicited a significant decline in superoxide anion production in diaphragm, gastrocnemius, and plasma, while inducing a further increase in inflammatory cells and internal nuclei in both muscles. Proinflammatory cytokines are differentially expressed in respiratory and limb muscles and plasma of CIH-exposed rats, while superoxide anion production increased in both muscle types and blood. Infliximab and NAC exerted different effects. These findings may help understand the biology underlying CIH in skeletal muscles and blood of patients with chronic respiratory diseases. J. Cell. Physiol. 232: 1165-1175, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Respiratory Medicine-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer, IMIM-Hospital del Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra, Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
authors.forename: Marisol
authors.initials: M
authors.lastname: Domínguez-Álvarez
authors.affiliation: Respiratory Medicine-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer, IMIM-Hospital del Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra, Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Gea
authors.affiliation: Respiratory Medicine-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer, IMIM-Hospital del Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra, Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Barreiro
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003964:Diaphragm / Q000378:metabolism* / Q000473:pathology*; D000860:Hypoxia / Q000097:blood* / Q000378:metabolism / Q000628:therapy*; D007249:Inflammation / Q000473:pathology*; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D016877:Oxidants / Q000378:metabolism*; D017208:Rats, Wistar; D013481:Superoxides / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053583:Interleukin-1beta; D015850:Interleukin-6; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007371:Interferon-gamma