title: A novel formulation of metal ions and citric acid reduces reactive oxygen species in vitro.
abstract: OBJECTIVE
  Reactive oxygen species, including superoxide anions, are thought to play an important role in impairing wound healing. Additionally, superoxide anions react with nitric oxide produced by macrophages to form peroxynitrite, another strong oxidant with detrimental effects on surrounding tissue. This in vitro study investigated whether samples of metal ions and citric acid are able to reduce levels of reactive oxygen species.
  
  
  METHODS
  Samples of materials were tested in assays for the following: inhibition of reactive oxygen species production by human polymorphonuclear neutrophils (PMNs); antioxidant activity (scavenging of superoxide anions in a cell-free system); inhibition of human complement (limiting the generation of complement factors that attract and stimulate PMNs, thereby reducing levels of reactive oxygen species).
  
  
  RESULTS
  Metal ions were shown to inhibit both PMN production of reactive oxygen species and the activation of complement via the classical pathway, whereas citric acid was found to be a scavenger of superoxide anions.
  
  
  CONCLUSIONS
  The beneficial effects of using formulations containing metal ions and citric acid on chronic wounds may be explained in part by a reduction of reactive oxygen species in these wounds.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Utrecht University, The Netherlands. A.J.J.vandenBerg@pharm.uu.nl
authors.forename: A J
authors.initials: AJ
authors.lastname: van den Berg
authors.forename: S B A
authors.initials: SB
authors.lastname: Halkes
authors.forename: H C Quarles
authors.initials: HC
authors.lastname: van Ufford
authors.forename: M J
authors.initials: MJ
authors.lastname: Hoekstra
authors.forename: C J
authors.initials: CJ
authors.lastname: Beukelman
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001681:Biological Assay / Q000379:methods; D019343:Citric Acid / Q000494:pharmacology*; D003165:Complement System Proteins / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007477:Ions; D008670:Metals / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D007477:Ions; D008670:Metals; D017382:Reactive Oxygen Species; D019343:Citric Acid; D003165:Complement System Proteins