Fig. 3.
In vivo inhibition of histone acetylation by garcinol improves survival and reduces injury in acute liver failure. (A) Kaplan-Meier survival curves of mice receiving 20 mg/kg/day of garcinol (n = 8) or saline (n = 5) for 5 days prior to the injection of the CD95-Ab. Means ± SDs are shown. Long-rank test p = 0.0473. (B) Western blotting for histone H3 (H3) and acetylated histone H3 (H3K9) on livers harvested 6 h after the administrations of CD95-Ab. β-actin was used as a loading control. (C) Densitometric quantifications of H3K9 over H3 from the Western blotting shown in B; t test; *p <0.05. (D) Representative TUNEL (upper panels) and H&E (lower panels) staining of livers harvested 6 h after the administrations of CD95-Ab or saline. (E) Quantifications of TUNEL-positive cells and (F) Necrotic areas on livers of at least three sections from each mouse (at least n = 4 mice per group). Means ± SDs are shown. Likelihood ratio test for generalized linear model: *p = 2.2 × 10−16. ANOVA plus Tukey’s post hoc test; for necrotic area: *p = 2.45 × 10−8. Enzyme activities of PDHC (G) and LDH (H) in nuclear fractions (nPDHC and nLDH) of livers harvested 6 h after CD95-Ab injections in mice treated with garcinol (n = 5) or saline (n = 4). Means ± SDs are shown. ANOVA plus Tukey’s post hoc test: p = 0.11 for nPDHC; p = 0.1 for nLDH. Ab, antibody; A.U., arbitrary units; nLDH, nuclear lactate dehydrogenase; nPDHC, nuclear pyruvate dehydrogenase complex; NS, not statistically significant; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling. (This figure appears in colour on the web.)