Fig. 8: The treatment of the Sirt6 activator prevented and treated APAP-induced hepatotoxicity.

A–E normal C57BL/6J mice were subjected to 3 days (once a day) pretreatment with vehicle or MDL-800 (100 mg/kg) and followed with the treatment with APAP (500 mg/kg) for 8 h. A Schematic of the experimental design. B Representative images showed the appearance of mouse livers. C H&E staining of liver sections from mice treated with vehicle or MDL-800. 10×, scale bar corresponds to 200 µm. Quantification of necrotic areas by ImageJ software. Results were presented as mean ± SEM (n = 6), ^**P < 0.01. D Serum ALT (left) and AST (right) activity in vehicle and MDL-800 treated mice. Each dot or triangle symbol represents a different mouse sample. Results were presented as mean ± SEM (n = 6), ^**P < 0.01. E JNK activation analyzed by Western blotting in WT mice treated with vehicle or MDL-800 (100 mg/kg). Results were presented as mean ± SEM (n = 3), ^**P < 0.01. F–I Normal C57BL/6J mice were treated with APAP (500 mg/kg) for 1 h then subjected intraperitoneal injected with MDL-800 (100 mg/kg), NAC (100 mg/kg) or vehicle separately and followed for 7 days to score the liver injury. F Schematic of the experimental design. G Representative images showed the appearance of mouse livers. H H&E staining of liver sections from mice treated with MDL-800 (100 mg/kg), NAC (100 mg/kg), or vehicle. 10×, scale bar corresponds to 200 µm. I Survival rate of mice. Normal C57BL/6J mice were treated with APAP (750 mg/kg) for 1 h, then subjected intraperitoneal injected with MDL-800 (100 mg/kg), NAC (100 mg/kg), or vehicle separately and followed for 66 h to score the survival rate (n = 10), ^**P < 0.01. Statistical analysis was performed by unpaired Student’s t test (C, D, E), and log-rank test (I).