Abstract / Summary
Abstract Acute lung injury (ALI) is a life-threatening condition marked by pulmonary inflammation and edema, with limited therapeutic options. SIRT1 protect against ALI, upon activation using SRT1720 and resveratrol, but exhibits limited bioavailability and specificity. We investigated the effectiveness of SIRT1 activation using tripeptide CWR in a lipopolysaccharide (LPS)-induced murine model of ALI. Pulmonary edema was determined by wet-to-dry lungs ratio. Hematoxylin and eosin (H&E) staining used to assess histopathological changes, while oxidative stress and mitochondrial integrity was quantified using respective biochemical assays for catalase, superoxide dismutase (SOD), lipid peroxidation and citrate synthase. Additionally, qPCR was performed to determine the expression levels of key pro-inflammatory cytokines and neutrophils infiltration was assessed by immunostaining. We observed that LPS administration resulted in more than 3 folds increase in the pulmonary damage and fluid accumulation, which was attenuated upon CWR treatment. LPS mediated neutrophils infiltration, release of inflammatory cytokines such as TNFα, IL-6, CCL3, CCL10 and mitochondrial impairment was alleviated through CWR administration. The study for the first time reported the protective effect of CWR in the murine model of ALI and lays the foundation for the future preclinical and clinical studies to explore its therapeutic potential.