title: Effect of potential therapeutic agents in reducing oxidative stress in pulmonary tissues of recurrent airway obstruction-affected and clinically healthy horses.
abstract: BACKGROUND
  To determine and compare the reactive oxygen and nitrogen species (ROS and RNS) in pulmonary tissues of horses affected with recurrent airway obstruction (RAO) and clinically healthy horses, and to evaluate the effectiveness of potential therapeutic agents in reducing ROS and RNS in the tissues of these horses.
  
  
  OBJECTIVE
  We hypothesised that RAO-affected horses would have high levels of reactive species and that the test agents would reduce them. The objectives were as follows: 1) to determine the level of ROS and RNS in pulmonary tissues (bronchial and arterial rings) of RAO-affected and clinically healthy horses; and 2) to determine the ability of pentoxifylline, pyrrolidine-dithiocarbamate and a combined use of endothelin A and B receptor antagonists (BQ123 and BQ788, respectively) in reducing reactive species.
  
  
  METHODS
  Arterial and bronchial rings were collected from the diaphragmatic lung lobe of each horse immediately after euthanasia. The levels of ROS and RNS were measured in control tissues and those incubated with test agents, using an electron paramagnetic resonance instrument.
  
  
  RESULTS
  The levels of ROS and RNS were significantly greater in arterial and bronchial tissues of RAO-affected than of clinically healthy horses. Pentoxifylline and endothelin antagonists reduced both ROS and RNS in tissues from RAO-affected horses. Basal levels of reactive species in clinically healthy horses were not affected by these agents. No difference in the level of reactive species was observed between arterial and bronchial tissues.
  
  
  CONCLUSIONS
  Horses affected by RAO had higher ROS and RNS than clinically healthy horses. Pentoxifylline and endothelin antagonists effectively reduced ROS and RNS in pulmonary tissues of RAO-affected horses.
  
  
  CONCLUSIONS
  The study suggested a potential use for pentoxifylline and endothelin antagonists in treating RAO-affected horses. As endothelin is involved in physiological functions, therapeutic use of its antagonists is cautioned.
authors.affiliation: Equine Health Studies Program, Department of Veterinary Sciences, School of Veterinary Medicine, Louisiana State University, LA, USA. cvenugopal@vetmed.lsu.edu
authors.forename: C
authors.initials: C
authors.lastname: Venugopal
authors.forename: N
authors.initials: N
authors.lastname: Mariappan
authors.forename: E
authors.initials: E
authors.lastname: Holmes
authors.forename: M
authors.initials: M
authors.lastname: Kearney
authors.forename: R
authors.initials: R
authors.lastname: Beadle
mesh_terms: D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D005260:Female; D006734:Horse Diseases / Q000378:metabolism*; D006736:Horses; D008168:Lung / Q000378:metabolism*; D008173:Lung Diseases, Obstructive / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010431:Pentoxifylline / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011651:Pulmonary Artery / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013859:Thiocarbamates / Q000494:pharmacology*; D046509:Tissue Culture Techniques
chemical_list: D001993:Bronchodilator Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D011759:Pyrrolidines; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D010431:Pentoxifylline