Effect of potential therapeutic agents in reducing oxidative stress in pulmonary tissues of recurrent airway obstruction-affected and clinically healthy horses.
Abstract: 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.
© 2012 EVJ Ltd.
Publication Date: 2012-04-17 PubMed ID: 22506732DOI: 10.1111/j.2042-3306.2012.00566.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study examines the oxidative stress in lung tissues of horses suffering from recurrent airway obstruction (RAO), also known as “heaves,” compared to healthy horses. It also investigates the effects of several therapeutic agents in reducing said stress. Using tissue samples from euthanized horses, the research team found greater levels of reactive species in RAO-affected horses and that certain drugs, like Pentoxifylline and endothelin antagonists, can effectively reduce these levels.
Objectives and Hypothesis
- The researchers proposed that horses inflicted with RAO would have elevated levels of reactive oxygen and nitrogen species (ROS and RNS) compared to healthy horses.
- They also anticipated that the tested agents – pentoxifylline, pyrrolidine-dithiocarbamate, and endothelin receptor antagonists (BQ123 and BQ788) – would effectively curb these heightened reactive species levels.
Methods
- The study collected arterial and bronchial tissue samples from the diaphragmatic lung lobes of each horse immediately after euthanization.
- These tissues were then used to measure the levels of ROS and RNS, first as control (untreated) cases and again after they were treated with the tested agents.
- The measuring was accomplished using an electron paramagnetic resonance instrument.
Results
- The findings reflected the hypothesis: RAO-affected horses showed significantly higher levels of ROS and RNS in their arterial and bronchial tissues compared to healthy horses.
- Pentoxifylline and the endothelin antagonists helped reduce both ROS and RNS within tissues collected from RAO-affected horses.
- By contrast, these treatment agents did not influence the basal levels of reactive species within healthy horses’ tissues.
- The study also found no variation in ROS and RNS levels between arterial and bronchial tissues.
Conclusions
- Clearly, RAO-affected horses demonstrate greater presence of ROS and RNS than horses without this condition.
- Notably, pentoxifylline and endothelin antagonists effectively lower these heightened ROS and RNS levels in the pulmonary tissues of afflicted horses.
- However, since endothelin fulfills significant physiological roles, any therapeutic use of its antagonists should be considered carefully.
- In conclusion, the research suggests potential uses for pentoxifylline and endothelin antagonists in the treatment of RAO in horses, pending careful administration and considerations of the functions of endothelin in the body.
Cite This Article
APA
Venugopal C, Mariappan N, Holmes E, Kearney M, Beadle R.
(2012).
Effect of potential therapeutic agents in reducing oxidative stress in pulmonary tissues of recurrent airway obstruction-affected and clinically healthy horses.
Equine Vet J, 45(1), 80-84.
https://doi.org/10.1111/j.2042-3306.2012.00566.x Publication
Researcher Affiliations
- Equine Health Studies Program, Department of Veterinary Sciences, School of Veterinary Medicine, Louisiana State University, LA, USA. cvenugopal@vetmed.lsu.edu
MeSH Terms
- Animals
- Bronchodilator Agents / pharmacology
- Female
- Horse Diseases / metabolism
- Horses
- Lung / metabolism
- Lung Diseases, Obstructive / metabolism
- Lung Diseases, Obstructive / veterinary
- Male
- Oligopeptides / pharmacology
- Oxidative Stress / drug effects
- Oxidative Stress / physiology
- Pentoxifylline / pharmacology
- Peptides, Cyclic / pharmacology
- Piperidines / pharmacology
- Pulmonary Artery / metabolism
- Pyrrolidines / pharmacology
- Reactive Nitrogen Species
- Reactive Oxygen Species
- Thiocarbamates / pharmacology
- Tissue Culture Techniques
Citations
This article has been cited 5 times.- Davis KU, Sheats MK. The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses. Inflammation 2021 Apr;44(2):450-465.
- Martin EM, Messenger KM, Sheats MK, Jones SL. Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes. Front Vet Sci 2017;4:160.
- Stokol T, Serpa PBS, Zahid MN, Brooks MB. Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation. Front Vet Sci 2016;3:99.
- Sunil VR, Vayas KN, Cervelli JA, Malaviya R, Hall L, Massa CB, Gow AJ, Laskin JD, Laskin DL. Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation. Exp Mol Pathol 2014 Aug;97(1):89-98.
- Cocco R, Sechi S, Rizzo M, Arrigo F, Giannetto C, Piccione G, Arfuso F. Assessing the Peripheral Levels of the Neurotransmitters Noradrenaline, Dopamine and Serotonin and the Oxidant/Antioxidant Equilibrium in Circus Horses. Animals (Basel) 2024 Aug 14;14(16).
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