Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

Figure 2 Inhibition of the p53/glutathione peroxidase 4/gasdermin D signaling pathway attenuates acute liver failure in vivo. A: Macroscopic examinations of mouse livers and microscopic examinations of liver sections stained with hematoxylin and eosin (100 ×); B: Administration of pifithrin-α and liproxstatin-1 and gasdermin D (GSDMD) knockout improved the median survival in mice treated with D-galactosamine/lipopolysaccharide; C: Detection of interleukin (IL)-1β, tumour necrosis factor alpha, IL-6, IL-2, and C-C motif ligand 2 in mouse serum with multi-factor kit. Data are presented as the mean ± SD of five independent experiments; D: Western blot analyses of p53, glutathione peroxidase 4 (GPX4), solute carrier family 7a member 11, Acyl-CoA synthetase long-chain family member 4 (ACSL4), and GSDMD proteins (n = 3 in each group). Data are presented as the mean ± SD of three independent experiments; E: Western blot analyses of GSDMD protein expression (n = 3 in each group). Data are presented as the mean ± SD of three independent experiments; F: IIron detection with an iron kit. Data are presented as the mean ± SD of five independent experiments; G: Quantitative real-time polymerase chain reaction analyses of p53, GPX4, SLC7A11, ACSL4, and GSDMD mRNA expression (n = 3 in each group). Data are presented as the mean ± SD of three independent experiments. ^aP < 0.05, ^bP < 0.01. ALF: Acute liver failure; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; IL: Interleukin; GPX4: Glutathione peroxidase 4; SLC7A11: Solute carrier family 7a member 11; ACSL4: Acyl-CoA synthetase long-chain family member 4; GSDMD: Gasdermin D; SIRT1: Silent information regulator sirtuin 1; LPS: Lipopolysaccharide; D-GalN: D-galactosamine.