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J Allergy Clin Immunol. 2010 Mar;125(3):626-35. doi: 10.1016/j.jaci.2009.10.065. Epub 2010 Feb 11.

Beneficial effects of high dose of L-arginine on airway hyperresponsiveness and airway inflammation in a murine model of asthma.

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  • 1Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma and Lung Disease, Institute of Genomics and Integrative Biology, Delhi, India.

Abstract

BACKGROUND:

Disturbance in the delicate balance between L-arginine-metabolizing enzymes such as nitric oxide synthase (NOS) and arginase may lead to decreased L-arginine availability to constitutive forms of NOS (endothelial NOS), thereby increasing the nitro-oxidative stress and airway hyperresponsiveness (AHR).

OBJECTIVE:

In this study, we investigated the effects of high doses of L-arginine on L-arginine-metabolizing enzymes and subsequent biological effects such as cyclic guanosine monophosphate production, lipid peroxidation, peroxynitrite, AHR, and airway inflammation in a murine model of asthma.

METHODS:

Different doses of L-arginine were administered to ovalbumin-sensitized and challenged mice. Exhaled nitric oxide, AHR, airway inflammation, T(H)2 cytokines, goblet cell metaplasia, nitro-oxidative stress, and expressions of arginase 1, endothelial NOS, and inducible NOS in lung were determined.

RESULTS:

L-arginine significantly reduced AHR and airway inflammation including bronchoalveolar lavage fluid eosinophilia, T(H)2 cytokines, TGF-beta1, goblet cell metaplasia, and subepithelial fibrosis. Further, L-arginine increased ENO levels and cyclic guanosine monophosphate in lung and reduced the markers of nitro-oxidative stress such as nitrotyrosine, 8-isoprostane, and 8-hydroxy-2'-deoxyguanosine. This was associated with reduced activity and expression of arginase 1, increased expression of endothelial NOS, and reduction of inducible NOS in bronchial epithelia.

CONCLUSION:

We conclude that L-arginine administration may improve disordered nitric oxide metabolism associated with allergic airway inflammation, and alleviates some features of asthma.

PMID:
20153031
DOI:
10.1016/j.jaci.2009.10.065
[PubMed - indexed for MEDLINE]
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