N-acetylcysteine alleviates pulmonary alveolar proteinosis induced by indium-tin oxide nanoparticles in male rats: involvement of the NF-?B signaling pathway

Indium-tin oxide (ITO) was previously found to have a toxic effect on lung tissues, and oxidative stress and the inflammatory response are two important mechanisms of ITO-induced lung injury. N-acetylcysteine (NAC) has been found to exhibit antioxidant and anti-inflammatory properties. The current study aimed to evaluate the possible protective effects of NAC against ITO nanoparticle (Nano-ITO)-induced pulmonary alveolar proteinosis (PAP) in adult male Sprague-Dawley rats, especially via modulation of nuclear factor-kappa B (NF-kappa B) signaling. For this purpose, 50 rats were randomly allocated into five groups (10 rats each) as follows: (1) control group; (2) saline group; (3) NAC (200 mg/kg) group; (4) PAP model group receiving a repeated intratracheal dose of Nano-ITO (6 mg/kg); and (5) PAP model+NF-kappa B inhibitor (NAC) group pre-treated intraperitoneally with NAC (200 mg/kg) twice per week before the administration of an intratracheal dose of Nano-ITO (6 mg/kg). Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and biochemical investigations. A 6 mg/kg dose of Nano-ITO markedly altered the levels of some oxidative stress biomarkers. The histological examination of Nano-ITO-exposed rats demonstrated diffused alveolar damage that involved PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. The immunohistochemical results of Nano-ITO-exposed rats revealed strongly positive NF-kappa B p65 and inhibitory kappa B kinase (IKK)-beta and weakly positive inhibitor of kappa-B subunit alpha (I kappa B-alpha) staining reactivity in the nuclei of cells lining the epithelium of the bronchioles and alveoli. Moreover, Nano-ITO activated the NF-kappa B pathway. However, pre-treatment with NAC significantly attenuated Nano-ITO-evoked alterations in the previously mentioned parameters, highlighting their antioxidant, anti-inflammatory, and anti-apoptotic potential. The results indicated that the degree of pul-monary fibrosis and proteinosis in the NAC-treated group was improved compared with that in the Nano-ITO-induced PAP model group. The level of malondialdehyde was also decreased overall in the NAC-treated group compared with that in the Nano-ITO-induced model group, indicating that the pulmonary fibrosis degree and oxidation levels were decreased. The present study also demonstrated that NAC increased the activity of anti-oxidant enzyme superoxide dismutase and total antioxidant capacity, indicating that it could alleviate oxidative stress in the lung tissue of Nano-ITO-exposed rats. In addition, NAC reduced the production of pro-inflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, and increased the levels of anti-in-flammatory factor IL-10. The current study demonstrated that NAC can effectively attenuate Nano-ITO-induced lung injury by reducing oxidative damage and the inflammatory response.

Automated summary

The study demonstrates that NAC can effectively attenuate lung injury induced by Nano-ITO by reducing oxidative damage and the inflammatory response.