Fig. 7: Blocking purine biosynthesis prevents liver damage by ethanol administration-induced reductive stress.
From: Identification of purine biosynthesis as an NADH-sensing pathway to mediate energy stress
a Schematic diagram illustrating the acute ethanol gavage model (top) and lentivirus-mediated LbNOX expression in liver tissue (bottom). 6-MP (100 mg/kg) and PTrexol (10 mg/kg) were pre-injected into the tail vein for 1 h and lentivirus (3*108 PFU) were pre-injected into the tail vein for 3 days. Mice were sacrificed after ethanol (6 g/kg) gavage for 9 h. b Effects of acute ethanol gavage on the ratio of NADH/NAD+ and NADPH/NADP+. From left to right: **P = 0.00012, **P = 8.67e-06, **P = 0.00012, **P = 0.00026. c Effects of acute ethanol gavage on liver tissue IMP, AMP, and GMP levels detected by LC/MS. From left to right: for IMP, **P = 0.00029, **P = 0.00020, **P = 0.00103, **P = 1.29e-05; for AMP, **P = 8.41e-05, *P = 0.01049, **P = 0.00064, **P = 0.00023; for GMP, **P = 8.11e-06, **P = 0.00165, **P = 0.00021, **P = 2.15e-05. d Effects of acute ethanol gavage on liver tissue ATP levels. From left to right: **P = 3.58e-06, **P = 0.00011, **P = 8.46e-08, **P = 0.00027. e Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in ethanol gavage groups versus control groups. From left to right: for ALT, **P = 4.03e-05, **P = 0.00055, **P = 0.00062, **P = 5.78e-05; for AST, **P = 0.00111, *P = 0.00277, **P = 0.00248, **P = 0.00042. f, g Imaging f and quantitation g of liver cell death detected by TUNEL staining after acute ethanol gavage for 9 h. Scale bar, 25 µm. From left to right: **P = 2.56e-05, **P = 1.22e-05, **P = 2.41e-06, **P = 6.21e-07. H2O group (n = 4 biologically independent animals) and ethanol group (n = 6 biologically independent animals). c–e, g Boxes represent minima to maxima (line at median) with whiskers at 1.5*IQR. *P < 0.05, **P < 0.01; Two-tailed Student’s t-tests. Source data are provided as a Source Data file.
