Bronchial oxidative stress in equine recurrent airway obstruction
Authors: Venugopal Changaram, Mariappan Nithya, Holmes Earnestine, Francis Joseph, Eades Susan
Journal: The FASEB Journal
Summary
# Oxidative Stress in Equine Recurrent Airway Obstruction: Implications for Anti-Inflammatory Therapy Recurrent airway obstruction (RAO) in horses is driven significantly by excessive reactive oxygen species (ROS) released from inflammatory cells, which perpetuate airway inflammation through altered cell signalling and pro-inflammatory gene expression. Researchers measured ROS production directly from bronchial tissue rings harvested from both RAO-affected and clinically normal horses using electron paramagnetic resonance spectroscopy, whilst testing whether blocking two key inflammatory pathways—tumour necrosis factor-alpha (TNF-α) via pentoxifylline and nuclear factor-kappa B (NF-κB) via pyrrolidinedithiocarbamate—would reduce oxidative stress. Bronchial tissues from RAO-affected horses generated significantly higher ROS levels than those from unaffected animals, and importantly, both pentoxifylline and pyrrolidinedithiocarbamate reduced ROS production in tissue samples from both groups. These findings suggest that pentoxifylline, an already-used immunomodulatory agent in equine practice, may have therapeutic merit beyond its conventional applications by specifically targeting the oxidative cascade that underpins RAO pathogenesis. For practitioners, this work provides mechanistic support for considering TNF-α and NF-κB antagonism as treatment strategies, potentially offering a complementary approach to traditional airway management and corticosteroid therapy in RAO cases.
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Practical Takeaways
- •RAO is characterized by elevated oxidative stress from inflammatory cell activity; understanding this mechanism may guide development of new anti-inflammatory therapies
- •Pentoxifylline and PDTC show promise as potential therapeutic agents to reduce oxidative stress in RAO-affected horses, though clinical efficacy studies are needed
- •Targeting TNF-alpha and NF-kB signaling pathways may offer therapeutic opportunities for managing RAO in clinical practice
Key Findings
- •Total reactive oxygen species (ROS) production was significantly greater in bronchial rings from RAO-affected horses compared to unaffected horses
- •Pentoxifylline (TNF-alpha antagonist) reduced ROS levels in bronchial rings from both RAO-affected and unaffected horses
- •PDTC (NF-kB inhibitor) reduced ROS levels in bronchial rings from both RAO-affected and unaffected horses
- •TNF-alpha and NF-kB pathways are implicated in oxidative stress mechanisms underlying RAO pathogenesis