Syringic Acid ameliorates Bleomycin induced Pulmonary Inflammation and Fibrosis in rats via maintenance of endogenous anti-oxidants and downregulation of pro-inflammatory markers

Abstract

Background: Chronic administration of bleomycin (BLM), a chemotherapeutic drug, has been linked to idiopathic pulmonary fibrosis (IPF). It has been observed that syringic acid, a phenolic compound, has antiapoptotic, anti-inflammatory, and antioxidant properties. To assess syringic acid's therapeutic potential against lung fibrosis caused by BLM and determine a potential mechanism of action. Methods: Sprague-Dawley rats were inducted into IPF after receiving 7.5 IU/kg of BLM intratracheally. Syringic acid (50 mg/kg, i.p.) was administered to rats for 14 days, after which different parameters in the lung and bronchoalveolar lavage fluid (BALF) were measured. Results: Altered BALF differential cell counts, elevated lung index, hydroxyproline, NO, and MDA plasma levels, and reduction in GSH, GPx, SOD, and CAT in group receiving BLM were evidence of pulmonary toxicity. Administering 50 mg/kg of syringic acid significantly reduced (p < 0.001) the changes brought about by BLM. The expression of TNF-α was greatly reduced by syringic acid when it was stimulated by BLM. The BLM-treated group's histological analysis revealed significant lung damage with alveolar septal thickening, interstitial infiltration, collapsing alveolar gaps, and an elevated Ashcroft and Szapiel score. Syringic acid was used to lessen these effects. The syringic acid group (p<0.01) markedly reduced Szapiel score, collagen deposition, lung edema, and fibrotic alterations. It also inhibited the infiltration of myofibroblasts and inflammatory cells, primarily macrophages and lymphocytes. By inhibiting the TGF-β1/NF-κB pathways, syringic acid mitigates BLM-induced IPF. This, in turn, improves the control of oxidant and pro-inflammatory markers (TNF-α) to decrease collagen deposition during pulmonary fibrosis. Conclusion: Finally, it is concluded that Syringic acid can protect the lung against BLM-induced pulmonary oxidative stress, inflammation and fibrosis.