Dasatinib Attenuates Inflammatory Outcomes of the Sepsis Induced Acute Lung Injury Through mTOR Pathway

Abstract

This study aimed to investigate the therapeutic potential of dasatinib, an FDA-approved drug for chronic myeloid leukemia, in sepsis-induced acute lung injury (ALI). In the in vitro part of the study, RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS), and the anti-inflammatory effects of dasatinib were assessed by measuring pro-inflammatory mediators and cytokines. In the in vivo part, ALI was induced in mice through intraperitoneal LPS injection. The researchers investigated alveolar-capillary permeability, the inflammatory response, and the therapeutic efficacy of dasatinib in ALI. Dasatinib administration was found to attenuate inflammation by inhibiting the mTOR pathway. In the in vivo experiments, dasatinib reduced the levels of pro-inflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF). It also decreased lung tissue permeability, as evidenced by a lower amount of Evans blue dye detected after ALI. Furthermore, dasatinib alleviated lung histological damage and reduced the lung injury grade, demonstrating its protective role in ALI. By inhibiting the mTOR pathway in macrophages, dasatinib exhibited a protective and anti-inflammatory effect on ALI. It reduced the intrapulmonary inflammatory response, prevented capillary disruption, and inhibited the accumulation of inflammatory cells. These findings suggest that dasatinib holds promise as a potential treatment option for protecting lung tissue in ALI.