Valproic Acid Inhibits NA-K-2CL Cotransporter RNA Expression in Male But Not in Female Rat Thymocytes

Abstract

Objective: The NKCC1 is a recognized tumorigenesis marker as it is important for tumor cell proliferation, differentiation, apoptosis, and tumor progression. The study aim was to investigate the effect of sodium valproate (VPA) on thymus NKCC1 RNA expression. Material and Methods: Wistar rats, age 4 to 5 weeks, were investigated in the control and VPA-treated male and female gonad-intact and castrated groups. The treatment duration with VPA 300 mg/kg/d was 4 weeks. Rat thymus was weighted; its lobe was taken for the expression of NKCC1 RNA determined by the real-time polymerase chain reaction method. Results: The RNA expression of the Slc12a2 gene was found to be significantly higher in the gonad-intact male control compared with the gonad-intact female control ( P = .04). There was a gender-related VPA treatment effect on NKCC1 RNA expression in thymus: The Slc12a2 gene RNA expression level was found to be decreased in VPA-treated gonad-intact males ( P = .015), and no significant VPA effects were found in the castrated males and in the gonad-intact and castrated females compared with the respective controls ( P > .05). Conclusions: The study showed a gender-related difference in the NKCC1 RNA expression in rat thymus. The VPA decreases the NKCC1 expression in the thymus only in gonad-intact male rats. The NKCC1 RNA expression downregulation by VPA could be important for further VPA pharmacological studies in oncology.