FIG. 9.

In vivo administration of the NFκB inhibitor BAY 11-7082 protected from APAP-mediated acute hepatotoxicity. Overnight fasted wild-type mice were i.p. injected physiological saline (vehicle) or 300 mg/kg APAP or BAY 11-7082 (5 mg/kg) 1 h prior APAP intoxication. Mice were sacrificed after 6 h and livers and serum were collected. (A) Nuclear p65-NFκB and Lamin B as loading control. Blots were quantified and results are expressed as fold change relative to vehicle (saline)-treated mice. Values are mean ± SEM. Statistical analysis was performed by one-way ANOVA followed by Newman–Keuls test. *p < 0.05 versus control (vehicle)-treated mice, ^#p < 0.05 versus APAP-treated mice. n = 5 mice per group. (B) Representative images of hematoxylin and eosin staining (upper panels) or anti-SIRT1 immunostaining (lower panels) in liver sections from wild-type mice treated with APAP or injected BAY 11-7082 1 h prior APAP intoxication. Scale bars = 100 μm. (C) Plasma ALT levels measured in the same experimental conditions. Values are mean ± SEM. Statistical analysis was performed by one-way ANOVA followed by Bonferroni post hoc test. **p < 0.01 versus control (vehicle)-treated mice, ^##p < 0.01 versus APAP-treated mice. n = 5 mice per group. (D) SIRT1 protein levels detected in liver extracts. Blots were quantified and results are expressed as fold change relative to control (vehicle)-treated mice. Values are mean ± SEM. Statistical analysis was performed by one-way ANOVA followed by Bonferroni post hoc test. *p < 0.05 versus control (vehicle)-treated mice, ^##p < 0.01 versus APAP-treated mice. n = 5 mice per group. (E) Overnight fasted wild-type mice were i.p. injected physiological saline (vehicle) or 300 mg/kg APAP or BAY 11-7082 (5 mg/kg) 1 h after APAP intoxication. Mice were sacrificed after 6 h and livers and serum were collected. Representative images of hematoxylin and eosin staining (upper panels) or anti-SIRT1 immunostaining (lower panels) in liver sections. Scale bars = 100 μm. (F) Plasma ALT levels measured in the same experimental conditions. Values are mean ± SEM. Statistical analysis was performed by one-way ANOVA followed by Bonferroni post hoc test. *p < 0.05 versus control (vehicle)-treated mice, ^#p < 0.05 versus APAP-treated mice. n = 5 mice per group. (G) SIRT1 protein levels detected in liver extracts. Blots were quantified and results are expressed as fold change relative to APAP-treated mice. Values are mean ± SEM. *p < 0.05 versus control (vehicle)-treated mice, ^##p < 0.01 versus APAP-treated mice. n = 5 mice per group. H&E, hematoxylin and eosin. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars