Evaluation of the Protective Effects of Alpha-Lipoic Acid Against Zinc Oxide Nanoparticle-Induced Pulmonary Injury in Rats

Abstract

Background: Zinc oxide nanoparticles (ZnO-NPs) are widely utilized due to their biocompatibility and broad applications. However, their toxicity, including hepatotoxicity, pulmonary toxicity, and neurotoxicity, has been reported in a concentration-dependent manner. Aim of the work: This study aimed to evaluate protective effects of alpha-lipoic acid (ALA) against zinc oxide nanoparticles (ZnO-NP)- induced pulmonary damage in rats. Material and methods: A total of 28 rats were divided equally into four groups: negative control, ALA-treated (200 mg/kg of ALA orally for three weeks), ZnO-NPs-treated (single intraperitoneal injection of 1000 mg/kg) and ZnO-NPs + ALA groups. Lung tissue homogenates were analyzed for oxidative stress markers (SOD, MDA, GPX1), inflammatory cytokines (TNF-α, IL-6), and gene expression of fibrosis and immune response markers (Ncr3, SMAD2, SMAD3, SMAD7, MMP9, Col 1A1, Fibronectin, MCP-1, TGF-β1, IL-10). Histopathological analysis was conducted using light, electron, and immunohistochemical techniques for CD68 and NF-κB. Results: The results showed that the ZnO-NPs + ALA group exhibited significantly higher SOD and GPX1 and lower MDA, TNF-α, and IL-6 levels compared to the ZnO-NPs group. Gene expression analysis demonstrated reduced expression of TGF-β1, Ncr3, SMAD2, SMAD3, MMP9, Col 1A1, Fibronectin, and MCP-1 in the ZnO-NPs + ALA group, whereas SMAD7 and IL-10 expression were elevated. Conclusion: Our findings demonstrated that ALA co-treatment improved the histological and ultrastructural changes in the lungs. Histomorphometric measurements showed that ALA significantly reduced the expression of the CD68 and NF-κB immunological proteins. By lowering oxidative stress, inflammation, and fibrosis-related gene expression, ALA successfully lessens ZnO-NP-induced pulmonary injury, demonstrating its promise as a preventive agent against lung damage by nanoparticles.