FIG. 1.

SIRT1 levels are decreased in the liver of humans and mice on acute APAP treatment. (A) Representative anti-SIRT1 immunostaining in human liver sections from five individuals with severe APAP intoxication that required liver transplantation and from a healthy individual as control. Scale bars = 100 μm. (B) SIRT1 protein levels in liver extracts from wild-type mice i.p. injected 300 mg/kg APAP or saline for 3 or 6 h. Graph depicts SIRT1 densitometric quantification. After quantification of all blots, results are expressed as fold change relative to the saline-injected condition and are mean ± SEM. Statistical analysis was performed by one-way ANOVA followed by Bonferroni post hoc test. *p < 0.05 versus saline-injected mice. n = 5–6 mice per group. (C) Overnight fasted mice were i.p. injected physiological saline (vehicle) or 300 mg/kg APAP. After 6 h, mice were sacrificed. Liver sections were stained against SIRT1 protein. Scale bars = 100 μm. ANOVA, analysis of variance; APAP, acetaminophen; i.p., intraperitoneal; SEM, standard error of the mean; SIRT1, sirtuin 1. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars