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


CONCLUSIONS
We conclude that L-arginine administration may improve disordered nitric oxide metabolism associated with allergic airway inflammation, and alleviates some features of asthma.
Mabalirajan
Ulaganathan
U
Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma and Lung Disease, Institute of Genomics and Integrative Biology, Delhi, India.
Ahmad
Tanveer
T
Leishangthem
Geeta Devi
GD
Joseph
Duraisamy Arul
DA
Dinda
Amit Kumar
AK
Agrawal
Anurag
A
Ghosh
Balaram
B
D000818:Animals; D001119:Arginase / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000188:drug therapy; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C544448:Arg1 protein, mouse; D001119:Arginase