title: Targeted aerosolized delivery of ascorbate in the lungs of chlorine-exposed rats.
abstract: BACKGROUND
  Chlorine (Cl(2))-induced lung injury is a serious public health threat that may result from industrial and household accidents. Post-Cl(2) administration of aerosolized ascorbate in rodents decreased lung injury and mortality. However, the extent to which aerosolized ascorbate augments depleted ascorbate stores in distal lung compartments has not been assessed.
  
  
  METHODS
  We exposed rats to Cl(2) (300 ppm for 30 min) and returned them to room air. Within 15-30 min postexposure, rats breathed aerosolized ascorbate and desferal or vehicle (mean particle size 3.3 μm) through a nose-only exposure system for 60 min and were euthanized. We measured the concentrations of reduced ascorbate in the bronchoalveolar lavage (BAL), plasma, and lung tissues with high-pressure liquid chromatography, protein plasma concentration in the BAL, and the volume of the epithelia lining fluid (ELF).
  
  
  RESULTS
  Cl(2)-exposed rats that breathed aerosolized vehicle had lower values of ascorbate in their BAL, ELF, and lung tissues compared to air-breathing rats. Delivery of aerosolized ascorbate increased reduced ascorbate in BAL, ELF, lung tissues, and plasma of both Cl(2) and air-exposed rats without causing lung injury. Based on mean diameter of aerosolized particles and airway sizes we calculated that approximately 5% and 1% of inhaled ascorbate was deposited in distal lung regions of air and Cl(2)-exposed rats, respectively. Significantly higher ascorbate levels were present in the BAL of Cl(2)-exposed rats when aerosol delivery was initiated 1 h post-Cl(2).
  
  
  CONCLUSIONS
  Aerosol administration is an effective, safe, and noninvasive method for the delivery of low molecular weight antioxidants to the lungs of Cl(2)-exposed individuals for the purpose of decreasing morbidity and mortality. Delivery is most effective when initiated 1 h postexposure when the effects of Cl(2) on minute ventilation subside.
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bracher
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Doran
authors.forename: Giuseppe L
authors.initials: GL
authors.lastname: Squadrito
authors.forename: Edward M
authors.initials: EM
authors.lastname: Postlethwait
authors.forename: Larry
authors.initials: L
authors.lastname: Bowen
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002713:Chlorine / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D000975:Antioxidants; D002713:Chlorine; D001205:Ascorbic Acid