title: Valproic acid treatment attenuates caspase-3 activation and improves survival after lethal burn injury in a rodent model.
abstract: Burn injury may result in multiple organ dysfunction partially because of apoptotic cell death. The authors have previously shown that valproic acid (VPA) improves survival in a dog burn model. The aim of this study is to examine whether a VPA improves survival in a rodent burn model and whether this was because of inhibition of cell apoptosis. Rats were subjected to third-degree 55% TBSA burns and randomized to treatment with a VPA (300 mg/kg) or normal saline. One group of animals was monitored for 12 hours for survival analysis; another group was killed at 6 hours after injury, and brains, hearts, and blood samples were harvested for examination. Plasma creatine kinase (CK)-MB activities and neuron-specific enolase (NSE) levels were measured to evaluate the cardiac and brain damages. The effects of a VPA on acetylation of histone H3 and caspase-3 activation were also evaluated. Major burn injury resulted in a significant decrease in the acetylation of histone H3, and there was an increase in plasma CK-MB activities, NSE concentrations, and tissue levels of activated caspase-3. A VPA treatment significantly increased the acetylation of histone H3 and survival of the animals after major burn injury. In addition, a VPA treatment significantly attenuated the plasma CK-MB activities, an NSE concentrations, and inhibited caspase-3 activation after major burn injury. These results indicate that a VPA can attenuate cardiac and brain injury, and can improve survival in a rodent model of lethal burn injury. These protective effects may be mediated in part through the inhibition of caspase-3 activation.
authors.affiliation: From the *Laboratory of Shock and Organ Dysfunction and †Department of Clinical Laboratory, Burns Institute, The First Hospital Affiliated to the People's Liberation Army General Hospital, Beijing, China.
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Luo
authors.forename: Sen
authors.initials: S
authors.lastname: Hu
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Bai
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Wang
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Du
authors.forename: Zhi-Long
authors.initials: ZL
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Sheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002056:Burns / Q000188:drug therapy* / Q000201:enzymology*; D053148:Caspase 3 / Q000097:blood*; D003402:Creatine Kinase / Q000097:blood; D006657:Histones / Q000097:blood; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D006657:Histones; D014635:Valproic Acid; D003402:Creatine Kinase; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase