title: L-NAME and L-arginine differentially ameliorate cigarette smoke-induced emphysema in mice.
abstract: Nitric oxide (NO) represents one of the most important intra- and extracellular mediators and takes part in both biologic and pathologic processes. This study aimed to verify the treatment with an NO inhibitor and an NO substrate in pulmonary emphysema induced by cigarette smoke (CS) in a murine model. We compared N-acetylcysteine (NAC), a precursor of glutathione, to G-nitro-L-arginine-methyl ester or L-NAME (LN), which is an NO inhibitor, and to l-arginine (LA), which is a substrate for NO formation. Mice were divided into several groups: control, CS, CS + LN, CS + LA, and CS + NAC. Control and CS groups were treated daily with a vehicle, while CS + LN, CS + LA, and CS + NAC groups were treated daily with LN (60 mg/kg), LA (120 mg/kg) and NAC (200 mg/kg), respectively. The bronchoalveolar lavage was analyzed and the lungs were removed for histological and biochemical analysis. CS increases neutrophil number. Neutrophil number was lowest in CS + LN, followed by CS + LA. The lungs of CS + LN, CS + LA and CS + NAC mice were protected compared to the lungs of CS mice, but not equal to the quality of lungs in control mice. The CS group also exhibited increased oxidative stress, which was also present in the CS + LN group and to a lesser extent in the CS + LA group. Tissue inhibitor of metalloproteinase 1 and 2 increased in the CS + LN group and to a lesser extent in the CS + LA group relative to the control group. These results suggest that LN and LA treatment protected the mouse lung from CS. However, NAC treatment was more than LN and LA. We suggest that the protection conferred by LN treatment requires a balance between proteases and antiproteases, and that protection conferred by LA treatment involves the balance between oxidants and antioxidants.
authors.affiliation: Institute of Biomedical Science, Federal University of Rio de Janeiro, Brazil. samuelv@ufrj.br
authors.forename: Samuel Santos
authors.initials: SS
authors.lastname: Valença
authors.forename: Carlos Romualdo
authors.initials: CR
authors.lastname: Rueff-Barroso
authors.forename: Wagner Alves
authors.initials: WA
authors.lastname: Pimenta
authors.forename: Adriana Correa
authors.initials: AC
authors.lastname: Melo
authors.forename: Renata Tiscoski
authors.initials: RT
authors.lastname: Nesi
authors.forename: Marco Aurélio Santos
authors.initials: MA
authors.lastname: Silva
authors.forename: Luís Cristóvão
authors.initials: LC
authors.lastname: Porto
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011656:Pulmonary Emphysema / Q000209:etiology / Q000517:prevention & control*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D016877:Oxidants; D012906:Smoke; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine