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Oral N-Acetylcysteine Attenuates Elastase-Induced Pulmonary Emphysema in Rats^*

^* From the Laboratorio Neumología Experimental, Servicio de Neumología, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.

Correspondence to: Nicolás González Mangado, MD, PhD, Servicio de Neumología, Fundación Jiménez Díaz Avda/ Reyes Católicos, 2 28040-Madrid, Spain; e-mail: ngonzalez{at}fjd.es

Study objective: To study the effect of the antioxidant N-acetylcysteine (NAC) in the development of elastase-induced emphysema in rats.

Materials and methods: Wistar rats (n = 72) were orotracheally instilled with 75 IU elastase or saline solution. Eighteen rats from each group received the antioxidant NAC from 2 days before induction of the lesion until they were killed 2, 8, and 28 days after instillation. The effects of treatment were assessed by measuring collagen content for the left lung, a histopathology evaluation (ie, mean alveolar internal surface area (AIA) and mean linear intercept measurement), and lung function.

Results: Twenty-eight days after elastase instillation, rats treated with NAC showed significant attenuation of the lesion in comparison with rats treated only with elastase, including the following: normalization of mean (± SEM) collagen content (1.23 ± 0.09 vs 1.51 ± 0.10 mg per left lung, respectively; p < 0.05); partial inhibition of mean AIA (14,860 ± 1,135 vs 19,622 ± 1,294 µm², respectively; p < 0.05) and mean linear intercept (108.8 ± 3.7 vs 123.0 ± 4.2 µm, respectively; p < 0.05); and increases and improvement in expiratory flows (27.8 ± 1.2 vs 23.4 ± 1.3 mL/s, respectively; p < 0.05). NAC was not able to avoid the compliance increase in the elastase-plus-NAC group.

Conclusion: Consistent with the results of anatomic, pathologic, and functional studies, NAC is able to attenuate the lesions induced by elastase in rats, which is in accordance with previous data supporting the idea that oxidant injury could contribute to the development of elastase-induced emphysema.

Key Words: elastase • emphysema • lung function • N-acetylcysteine • rats

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