Gender-Related Effect of Sodium Dichloroacetate on the Number of Hassall’s Corpuscles and RNA NKCC1 Expression in Rat Thymus

Abstract

The aim was to investigate the effect of dichloroacetate (DCA) on thymus weight, Hassall’s corpuscle number (HCs), and NKCC1 RNA expression in Wistar rats aged 4–5 weeks. They were investigated in the controls and DCA-treated gonad-intact and castrated males and females. The treatment lasted 4 weeks with DCA 200 mg/kg/day. At the end of the experiment, rat thymus was weighted, and its lobe was taken for the expression of NKCC1 RNA determined by the PCR method and of Hassall’s corpuscles by immunohistochemistry. DCA caused a thymus weight decrease in DCA-treated gonad-intact rats of both genders as compared with their controls (p < 0.05), and no such impact was found in castrated DCA-treated males and females. DCA caused an increase of the HCs in gonad-intact males (p < 0.05), and no such increase in the DCA-treated gonad-intact females was found. There was gender-related difference in the HCs when comparing DCA-treated gonad-intact males and females: males showed significantly higher HCs (p < 0.05); no gender-related differences were found in the castrated DCA-treated groups. The Slc12a2 gene RNA expression level was found to be significantly decreased only in gonad-intact and in castrated DCA-treated males. The authors discuss the gender-related DCA effects on the thymus.

The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo

“…The gender-related DCA effect on differences in the NKCC1 gene ( Slc12a2 ) expression in rat thymus was reported: the NKCC1 RNA expression levels in DCA-treated gonad-intact and castrated males were significantly decreased, and no such effect was determined in the gonad-intact and castrated female DCA-treated rats [8,69]. Sodium dichloroacetate treatment caused thymus weight decrease in gonad-intact male and female rats, but no such treatment impact was determined in castrated DCA-treated males and females [69]. This could indicate a synergistic effect of DCA with gonad hormones on thymocyte proliferation [70].…”

“…Sodium dichloroacetate treatment caused a significant Hassall’s corpuscle (HC) number increase in the thymus of gonad-intact male rats, and no such effect was found in the gonad-intact females. However, no gender-related difference was found in the castrated rats of both genders [69]. Hassall’s corpuscles represent an indirect differentiation feature of thymus epithelial cells [85,86] and thymocytes apoptosis [87,88].…”

Preclinical Study in Mouse Thymus and Thymocytes: Effects of Treatment with a Combination of Sodium Dichloroacetate and Sodium Valproate on Infectious Inflammation Pathways

“…DCA–VPA treatment also did not affect thymus weight in mice (0.118 ± 0.011 g in the control and 0.118 ± 0.028 g in the treated group; p > 0.05). Previously, we reported that 4 weeks of monotherapy with DCA, at twice the dose of the DCA–VPA combination, caused a thymus weight decrease in DCA-treated gonad-intact male rats compared with their control, and no such impact was found in castrated DCA-treated males [ 54 ]. Also, VPA monotherapy at twice the dose of the DCA–VPA combination significantly reduced the thymus weight of castrated male Wistar rats after 4 weeks of treatment.…”

“…Mice were treated with a drinking aqueous solution of the DCA–VPA combination (DCA 100 mg/kg and VPA 150 mg/kg/day) for two weeks. Considering the synergistic mechanism of action of DCA and VPA, the doses of DCA and VPA were half the doses we previously reported administered to animals treated with monotherapy [ 54 , 55 ].…”

“…The thymus is responsible for generating T lymphocytes and is particularly vulnerable to infections [ 53 ]. Our previous research has shown that long-term monotherapy with DCA or VPA reduces the thymus weight of male Wistar rats [ 54 , 55 ].…”