Article / Tissue and Cell
Inhibition of pyroptosis by belnacasan: A potential strategy for mitigating acute lung injury and multiple organ dysfunction
Abstract
Acute lung injury (ALI) caused by infections and trauma poses a significant public health concern. The activation of caspase-1 triggers the expression of interleukin-1 beta (IL-1β), leading to pyroptosis. Targeting pyroptosis may offer therapeutic benefits in ALI. This study evaluates the therapeutic potential of belnacasan (Bel), a caspase-1 inhibitor, in reducing pyroptosis and mitigating multi-organ failure in a murine ALI model induced by lipopolysaccharide (LPS).
Methods
Thirty BALB/c mice were divided into five groups (n = 6): control, LPS, LPS+Bel, Bel, and DMSO. The LPS group received 5 mg/kg LPS, while the LPS+Bel group was treated with 50 mg/kg belnacasan one hour post-LPS. Histopathological, immunohistochemical, and ultrastructural analyses were conducted on lung tissues. Organ damage was assessed through histopathological evaluation and biochemical markers, including ALT/AST for livers and BUN/creatinine for kidneys. Inflammation was evaluated through C-reactive protein (CRP) levels. IL-1β levels in bronchoalveolar lavage fluid (BALF) were measured using ELISA, and alveolar macrophages were analysed via confocal microscopy.