Valproic acid prevents hemorrhage-associated lethality and affects the acetylation pattern of cardiac histones

摘要: Pharmacological inhibitors of histone deacetylases (HDAC) demonstrate cytoprotective effects both in vitro and vivo. In this study, we investigated whether valproic acid (VPA), a known mood stabilizer anticonvulsant with HDAC-inhibiting activity, improves survival following otherwise lethal hemorrhage rats. We found that preinsult injection VPA (300 mg/kg, twice) prolonged the severely hypotensive animals up to 5 times. treatment increased acetylation nonhistone proteins rat heart. The pattern modifications individual histones revealed hyperacetylation H2A, H3, H4, indicating presence active genes. Expression HSP70 superoxide dismutase, implicated modulation vitality, was by VPA. Our results reveal offers considerable protection hemorrhagic shock model suggest role for HDAC inhibition mediating actions.