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. 2023 Jun 20;14:3648. doi: 10.1038/s41467-023-39412-6

Fig. 7. Alleviating APAP-induced injury and mortality by inhibiting USP25.

Fig. 7

a Schematic of the experiment. Male C57BL/6 mice were fasted for 14 h, given APAP (300 mg/kg body weight), and CT1113 6 h later, for a total of 3 times (every 8 h). CT1113 was given through i.p. at half of the oral dose to achieve fast absorption and action. The animals were sacrificed at 24 h after APAP administration. b Serum ALT and AST levels. n = 6 mice per group. c Hematoxylin and eosin staining of the liver sections from mice in (a). Necrotic areas were encircled and quantified. n = 6 mice per group. Scale bar, 200 μm. d Schematic of the experiment. Male C57BL/6 mice were pretreated with CT1113 or vehicle (9 mice per treatment) 48 h before being fasted for 14 h, given high dose APAP (750 mg/kg body weight). The animals were observed continuously for up to 100 h after APAP administration. CT1113 treatment were continued for the rest of time until death or the end of the experiment. e Kaplan-Meier plot of the survival of the mice in (d). Error bars denote SEM. f Schematic illustration of the role of USP25 and its inhibitor in regulating the KEAP1-NRF2 signaling pathway to oppose APAP-induced liver injury. Error bars denote SEM. Two-tailed student’s t tests analysis (c), non-parametric tests with blue colored (b). Source data are provided as a Source Data file.