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.
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.
Our research was supported by special foundation of the 11 5-year plan for Chinese Military Medical Project, No.06Z055; and the National Basic Research Program of China (973 Program, Grant 2012CB518101). The sponsors were not involved in the study design, in the collection, analysis, and interpretation of data; in the writing of the article; or the decision to submit the article for publication.
Address correspondence to Sen Hu, MD, Laboratory of Shock and Organ Dysfunction, Burns Institute, The First Hospital Affiliated to the People’s Liberation Army General Hospital, 51 Fu Cheng Road, Beijing 100048, China.