l-Arginine reduces mitochondrial dysfunction and airway injury in murine allergic airway inflammation

Abstract

Bronchial epithelial injury is the hall mark of asthma which is a chronic airway inflammatory disease. We have shown the mitochondrial ultrastructural changes and dysfunction in bronchial epithelia of OVA induced mice. Reduced l-arginine bioavailability in asthma leads to increased formation of peroxynitrite which could induce mitochondrial dysfunction. We have also shown that l-arginine administration attenuates experimental asthma and reduces peroxynitrite. In this study, we wanted to determine the effect of l-arginine on mitochondrial dysfunction and airway injury in allergic airway inflammation. To determine this, l-arginine was administered to ovalbumin sensitized and challenged mice during allergen challenges. Mitochondrial and cytosolic fractions were purified from the lung to determine key mitochondrial functions, and mitochondrial ultrastructural changes in bronchial epithelia of first generation bronchi were determined. It was found that l-arginine administration increased mitochondrial cytochrome c oxidase activity, reduced cytosolic cytochrome c, increased lung ATP levels, reduced DNA fragmentation in bronchial epithelia and restored the ultrastructural changes of mitochondria of bronchial epithelia. In addition, l-arginine administration reduced the widening of intercellular spaces between adjacent bronchial epithelia. These findings indicated that l-arginine administration reduced airway injury and restored mitochondrial dysfunction in murine allergic airway inflammation.