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Updated: Jan 9, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Comparative Study of Histone Deacetylase Inhibitors for Radiation Protection Using Survival Outcomes in a Mouse Model
Yukiro Kurokawa1,2, Shinichi Watanabe2, Takaaki Yano1
1Division of Pharmacy, Ehime University Hospital, 454 Shitsukawa, Toon, Ehime 791-0295, Japan.
Abstract:
Histone deacetylases (HDACs) regulate chromatin structure and gene expression, and their inhibition has been proposed as a radioprotective strategy. However, few studies have compared multiple HDAC inhibitors (HDACis) under identical conditions. This study evaluated the efficacy of seven HDACis in a mouse total body irradiation (TBI) model. Male ICR mice received 7.5 Gy TBI followed by a single administration of valproic acid (VPA; 300 or 600 mg/kg), sodium butyrate (NaB; 500 or 1000 mg/kg), trichostatin A (TSA; 0.5 or 1.0 mg/kg), vorinostat (10 or 50 mg/kg), panobinostat (25 or 50 mg/kg), givinostat (5 or 10 mg/kg), or entinostat (25 or 50 mg/kg). Survival was monitored for 20 d. Only VPA at 600 mg/kg significantly improved survival compared with vehicle (overall p = 0.00241; p = 0.0039 vs. vehicle), while all other HDACis showed no significant benefit. VPA's efficacy may reflect a combination of effects on DNA repair, inflammation, and redox regulation rather than HDAC inhibition alone. These findings suggest VPA to be a promising candidate for radioprotection and emphasize the need for further studies to optimize dosing and explore underlying mechanisms.
Insights
Valproic acid (VPA) shows promise as a radioprotective agent, significantly improving survival after total body irradiation (TBI) in mice. Other HDAC inhibitors did not demonstrate similar benefits, highlighting VPA
Area of Science:
- Radiation oncology
- Molecular biology
- Pharmacology
Background:
- Histone deacetylases (HDACs) regulate gene expression and chromatin structure.
- HDAC inhibition is a potential radioprotective strategy.
- Limited comparative studies exist for different HDAC inhibitors (HDACis).
Purpose of the Study:
- To evaluate the efficacy of seven HDACis as radioprotective agents.
- To compare the effects of various HDACis under identical conditions.
- To identify promising HDACis for mitigating radiation damage.
Main Methods:
- A mouse model of total body irradiation (TBI) was used.
- Mice received 7.5 Gy TBI followed by administration of one of seven HDACis or vehicle.
- Survival was monitored for 20 days post-irradiation.
Main Results:
- Only valproic acid (VPA) at 600 mg/kg significantly improved survival.
- All other tested HDACis (NaB, TSA, vorinostat, panobinostat, givinostat, entinostat) showed no significant radioprotective benefit.
- VPA's efficacy may involve mechanisms beyond HDAC inhibition, such as DNA repair and redox regulation.
Conclusions:
- Valproic acid (VPA) demonstrates significant radioprotective potential in a mouse TBI model.
- The findings suggest VPA may offer benefits through multiple biological pathways.
- Further research is needed to optimize VPA dosing and elucidate its precise mechanisms for radioprotection.
