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Updated: Jun 1, 2026
Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
L-NAME and L-arginine differentially ameliorate cigarette smoke-induced emphysema in mice
Samuel Santos Valença1, Carlos Romualdo Rueff-Barroso, Wagner Alves Pimenta
1Institute of Biomedical Science, Federal University of Rio de Janeiro, Brazil. samuelv@ufrj.br
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.
Insights
Nitric oxide (NO) inhibition or supplementation, along with N-acetylcysteine (NAC), protected mouse lungs from cigarette smoke (CS) damage. NAC offered the most significant protection, suggesting complex roles for NO and oxidative stress in emphysema.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Pharmacology
Background:
- Nitric oxide (NO) is a key mediator in biological and pathological processes.
- Pulmonary emphysema, often induced by cigarette smoke (CS), involves complex inflammatory and oxidative pathways.
- Understanding NO's role is crucial for developing effective emphysema treatments.
Purpose of the Study:
- To investigate the therapeutic effects of inhibiting or supplementing nitric oxide (NO) in a mouse model of cigarette smoke-induced pulmonary emphysema.
- To compare the protective effects of an NO inhibitor (L-NAME), an NO substrate (L-arginine), and N-acetylcysteine (NAC) against CS-induced lung injury.
Main Methods:
- Pulmonary emphysema was induced in mice using cigarette smoke (CS).
- Mice were treated with L-NAME (NO inhibitor), L-arginine (NO substrate), or N-acetylcysteine (NAC).
- Bronchoalveolar lavage, lung histology, and biochemical analyses were performed to assess lung injury, inflammation, oxidative stress, and protease/antiprotease balance.
Main Results:
- CS exposure significantly increased neutrophil counts and oxidative stress in mouse lungs.
- L-NAME and L-arginine treatments reduced neutrophil counts and offered lung protection compared to CS alone, but did not fully restore lung health.
- NAC treatment demonstrated superior protection against CS-induced lung injury compared to L-NAME and L-arginine, with reduced oxidative stress.
- CS-induced increases in tissue inhibitors of metalloproteinase 1 and 2 were observed, particularly with L-NAME and L-arginine treatment.
Conclusions:
- Both NO inhibition and supplementation show protective effects in CS-induced emphysema, indicating NO's complex role.
- N-acetylcysteine (NAC) provides significant lung protection, potentially through mechanisms beyond direct NO modulation.
- Effective treatment may involve balancing protease-antiprotease and oxidant-antioxidant systems in the lung.
