The effect of valproic acid on SLC5A8 expression in gonad-intact and gonadectomized rat thymocytes

• Published in: International journal of immunopathology and pharmacology Vol. 36; p. 20587384211051954
• Main Authors: Juknevičienė, Milda, Balnytė, Ingrida, Valančiūtė, Angelija, Stanevičiūtė, Jūratė, Sužiedėlis, Kęstutis, Stakišaitis, Donatas
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-01-2022; Sage Publications Ltd
• Subjects: Animals; Anticonvulsants - pharmacology; Antiviral agents; Chloride transport; Drinking water; Fatty acids; Female; Females; Gender differences; Gene expression; Gene Expression - drug effects; Histones; Immunomodulation; Inflammation; Male; Males; Metabolism; Mitochondria; Monocarboxylic Acid Transporters - genetics; Orchiectomy; Original; Ovariectomy; Ovary; Polymerase chain reaction; Rats; Rats, Wistar; Rodents; Sex Characteristics; Testis; Thymocytes; Thymocytes - drug effects; Thymocytes - metabolism; Valproic acid; Valproic Acid - pharmacology; SLC5A8; valproic acid; sex-related difference; thymocyte
• ISSN: 0394-6320; 2058-7384
• DOI: 10.1177/20587384211051954

Background
Valproic acid (VPA) pharmacological mechanisms are related to the anti-inflammatory and anti-viral effects. VPA is a histone deacetylases inhibitor and serves a role in its immunomodulatory impacts. VPA has complex effects on immune cell’s mitochondrial metabolism. The SLC5A8 transporter of short fatty acids has an active role in regulating mitochondrial metabolism. The study aimed to investigate whether SLC5A8 expresses the sex-related difference and how SLC5A8 expression depends on gonadal hormones, VPA treatment, and NKCC1 expression in rat thymocytes.
Methods
Control groups and VPA-treated gonad-intact and gonadectomized Wistar male and female rats were investigated (n = 6 in a group). The VPA 300 mg/kg/day in drinking water was given for 4 weeks. The SLC5A8 (Slc5a8 gene) and NKCC1 (Slc12a2 gene) RNA expressions were determined by the RT-PCR method.
Results
The higher Slc5a8 expression was found in the gonad-intact males than respective females (p = 0.004). VPA treatment decreased the Slc5a8 expression in gonad-intact and castrated males (p = 0.02 and p = 0.03, respectively), and increased in gonad-intact female rats compared to their control (p = 0.03). No significant difference in the Slc5a8 expression between the ovariectomized female control and VPA-treated females was determined (p > 0.05). VPA treatment alters the correlation between Slc5a8 and Slc12a2 gene expression in thymocytes of gonad-intact rats.
Conclusion
VPA effect on the Slc5a8 expression in rat thymocytes is gender- and gonadal hormone-dependent.