Valproic acid suppresses SIRT1 inducing hepatotoxicity / 中国药理学通报

ABSTRACT

Aim To detect the role of sirtuin1 ( SIRT1 ) in hepatotoxity caused by valproic acid ( VPA) . Methods The changes of SIRT1 expression of HepG2 cells were detected by Western blot. And then SIRT1 plasmid or siRNA was transfected to con-struct SIRT1 overexpressed or knocked-down HepG2 cells. Furthermore, SRB assays were taken to observe the changes of viability of these cells exposed to VPA. Results VPA suppressed SIRT1 expression in a time and dose-dependent manner. SIRT1 overexpression showed a protective effect to the cytotoxicity caused by VPA, and the IC50 before and after transfection was (4. 025 ± 0. 47) and (10. 87 ± 1. 50) mmol·L-1 re-spectively. Moreover, transfection of SIRT1 siRNA sensitized HepG2 cells to VPA, and the IC50 before and after transfection was (1. 938 ± 0. 16) and (0. 663 ± 0. 05) mmol·L-1 respectively. Conclusion VPA suppressed SIRT1 expression in HepG2 cells and over-expression of SIRT1 could reduce cytotoxicity induced by VPA.