title: Hyperbaric oxygen reduces matrix metalloproteinases in ischemic wounds through a redox-dependent mechanism.
abstract: Little is known about the impact of hyperbaric oxygen treatment (HBOT) on matrix metalloproteinase (MMP) production in pre-existing high-oxidant wounds. This study aimed to investigate whether HBOT modulates reactive oxygen species (ROS) and MMP regulation in ischemic wound tissue. Using a validated ischemic wound model, Sprague-Dawley rats were divided into four groups for daily treatment: HBOT, N-acetylcysteine (NAC), HBO and NAC, and control (normoxia at sea level). High levels of inducible nitric oxide synthase (iNOS), gp91-phox, and 3-nitrotyrosine were detected in ischemic wounds, indicating high-oxidant stress. HBOT not only increased antioxidant enzyme expression, such as Cu/Zn-superoxide dismutase, catalase, and glutathione peroxidase, but also significantly decreased pro-oxidant enzyme levels, such as iNOS and gp91-phox, thereby decreasing net oxygen radical production by means of negative feedback. This effect was blocked by NAC treatment in ischemic wounds. HBO-treated ischemic wounds also manifested reduced phosphorylation of extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinase, and c-Jun, indicating downregulation of mitogen-activated protein kinases (MAPKs). Furthermore, HBOT decreased the expression of several MMPs while simultaneously increasing tissue inhibitor of MMP (tissue inhibitor of metalloproteinase 2). These results indicate that HBOT acts via the ROS/MAPK/MMP signaling axis to reduce tissue degeneration and improve ischemic wound healing.
authors.affiliation: Plastic Surgery Department, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Plastic Surgery Division, The University of Texas Medical Branch, Galveston, Texas, USA. Electronic address: lukeqixu@yahoo.com.
authors.forename: Qixu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Plastic Surgery Division, The University of Texas Medical Branch, Galveston, Texas, USA; Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Gould
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D006931:Hyperbaric Oxygenation / Q000379:methods*; D007511:Ischemia / Q000378:metabolism / Q000628:therapy*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000293:injuries* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000975:Antioxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase; D020782:Matrix Metalloproteinases