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Journal of Burn Care & Research:
doi: 10.1097/BCR.0b013e31828a8d32
Original Articles

Valproic Acid Treatment Attenuates Caspase-3 Activation and Improves Survival After Lethal Burn Injury in a Rodent Model

Luo, Hong-Min MD*; Hu, Sen MD*; Bai, Hui-Ying MD*; Wang, Hai-Bin MD; Du, Ming-Hua MD*; Lin, Zhi-Long MD*; Ma, Li MD*; Wang, Huan MD*; Lv, Yi MD*; Sheng, Zhi-Yong MD*

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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.

Copyright © 2013 by the American Burn Association

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