N-Acetylcysteine attenuated pulmonary fibrosis induced by bleomycin via immunomodulation responses

Zahra Maghsadi , Abbas Azadmehr , Ali Akbar Moghadamnia, Farideh Feizi, Negar Hamidi


Background and purpose: Pulmonary fibrosis (PF) is a chronic and life-threatening interstitial lung disease. N-acetyl cysteine (NAC) is an antioxidant pharmaceutically available to reduce endothelial dysfunction, inflammation, and fibrosis, however, the therapeutic effect of NAC on PF has not been clearly identified. This research aimed to investigate the possible therapeutic impact of NAC on PF induced by bleomycin in the rat model. 

Experimental approach: Rats received intraperitoneal injections of NAC at 150, 300, and 600 mg/kg for                   28 days before bleomycin, while the positive and negative control groups were treated with bleomycin alone and normal saline, respectively. Then, rats’ lung tissues were isolated and leukocyte infiltration and also collagen deposition were evaluated using hematoxylin and eosin and Mallory trichrome stainings, respectively. In addition, the levels of IL-17, and TGF-β cytokines in bronchoalveolar lavage fluid and hydroxyproline in homogenized lung tissues were assayed using the ELISA method.

Findings/Results: Histological findings indicated that NAC decreased leukocyte infiltration, collagen deposition, and fibrosis score in the bleomycin-induced PF tissue. Moreover, NAC significantly reduced               TGF-β and hydroxyproline levels at 300-600 mg/kg, as well as IL-17 cytokine at 600 mg/kg.

Conclusion and implications: NAC showed a potential anti-fibrotic effect by reducing hydroxyproline and TGF-β as well as an anti-inflammatory effect by decreasing IL-17 cytokine. So, it may be administered as a prophylactic or therapeutic candidate agent to attenuate PF via immunomodulatory effects. Although, future studies are suggested.


Bleomycin; Collagen; Cytokines; N-acetylcysteine; Pulmonary fibrosis.

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