Thymoquinone-PLGA-PVA Nanoparticles Ameliorate Bleomycin-Induced Pulmonary Fibrosis in Rats via Regulation of Inflammatory Cytokines and iNOS Signaling

SIMPLE SUMMARY: In this study, we evaluated the role of thymoquinone-PLGA-PVA nanoparticles (TQ-PLGA-PVA-NPs) in the amelioration of lung fibrosis induced experimentally in rats. Evaluation was performed via estimation of inflammatory cytokines in addition to the histopathological, immunohistochemical, and ultrastructural examination of lung tissues. Results illustrated the promising ameliorative role of TQ-PLGA-PVA-NPs. ABSTRACT: Pulmonary fibrosis is considered one of the most chronic interstitial illnesses which are not easily treated. thymoquinone’s (TQ) benefits are still partly problematic due to poor water solubility; therefore, it was loaded onto PLGA-PVA carriers. This study aimed to evaluate the potential effect of TQ-PLGA-PVA nanoparticles (TQ-PLGA-PVA-NPs) on pulmonary fibrosis induced by bleomycin in albino rats. Forty male rats were randomized into four groups. The first group served as the control group; the second and the third groups received bleomycin intratracheally, whereas the third group received TQ-PLGA-PVA-NPs after 4 weeks from bleomycin administration. The fourth group was administrated TQ-PLGA-PVA-NPs alone. The designed nanoparticles appeared around 20 nm size (10–30 nm), had a spherical shape, and had 80% encapsulation efficiency. The histological examination of rats simultaneously treated with TQ-PLGA-PVA-NPs and bleomycin revealed reduction in the thickness of the alveolar septa and improvement of the other lung structures, with the presence of lymphocytes admixed with exfoliated epithelium in a few lumina remaining. Ultrastructural findings revealed marked collagenolysis and the release of nanoparticles from ruptured pneumocytes within the alveolar septa after 14 days from TQ-PLGA-PVA-NPs administration. Very active pneumocyte types II were seen in the TQ-PLGA-PVANP group. Additionally, immunohistochemical expression of inducible nitric oxide (iNOS) and estimation of inflammatory cytokines in lung tissues including interleukin 10 (IL 10) and transforming growth factor-beta (TGF-β1) confirmed the antioxidant and anti-inflammatory effects of TQ-PLGA-PVANPs. The study concluded that TQ-PLGA-PVA-NPs could attenuate the bleomycin-induced pulmonary fibrosis, through the inhibition of lung inflammation and the suppression of bleomycin- induced oxidative stress.