An in vitro study of hepatotoxicity induced by valproic acid and its metabolites / 药学实践杂志

ABSTRACT

Objective To confirm the hepatotoxicity of valproic acid (VPA ) and its metabolites (2-propyl-4-pentenoic acid ,3-hydroxy valproic acid ,5-hydroxy valproic acid) on human liver cells .Methods Cells were divided into control group and VPA-treated group .The control group was conventionally cultured while the VPA-treated group was treated with valproic acid and its metabolites . The rate of cell proliferation was assayed by CCK 8 protocol . The mRNA levels of CYP1A1 , CYP1A2 ,PCNA ,Bax and Bcl-2 were measured by real time PCR .The correlated protein levels were measured by Western Blotting .The activity of LDH ,AST and ALT were also detected .Results Compared to the control group ,with the increases of concentrations and reaction time of VPA and its metabolites ,the proliferation rate of L02-cell was reduced ,the mRNA and protein levels of CYP1A1 ,CYP1A2 ,and Bax was increased ,the mRNA and protein level of PCNA and Bcl-2 was decreased , AST ,ALT ,and LDH were also elevated in the treated group .Conclusion Valproic acid and its metabolites were positively re-lated to hepatotoxicity .