Abstract
Aims: This study aimed to explore the potential protective effect of alpha-lipoic acid on busulfan-induced pulmonary fibrosis in rats.
Main methods: Eighteen adult male rats were divided into 3 groups; control, busulfan, and busulfan plus alpha-lipoic acid groups. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to the histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of alpha-smooth muscle actin (alpha-SMA), TNF-alpha, and Caspase 3 were determined immunohistochemically.The pulmonary expression of COX-2 and NOX-4 mRNA was assessed using qRT-PCR.
Key findings: Administration of ALA significantly protect the lung against BUS-induced pulmonary fibrosis, besides the up regulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition that associated with a decreased expression of alpha-SMA, TNF-alpha, and Caspase 3 in the lung tissues.Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.
Significance: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.