The protective effect of valproic acid on myocardium in rats with lethal scald injury and its mechanism

Abstract

To investigate the protective effects of valproic acid (VPA) on myocardium in rats following lethal burn injury and its mechanism. Seventy-eight Sprague-Dawley (SD) rats were randomly assigned to four groups: sham-scald group (n=10), sham-scald + VPA group (n=10), scald group (n=29), and scald + VPA group (n=29). Rats in the latter two groups were subjected to 55% total body surface area (TBSA) third-degree burns by immersing the back of the trunk for 15 seconds, both lower extremities for 15 seconds, and the abdomen for 8 seconds in 80 centigrade water. Sham-scald rats were immersed in 37 centigrade water instead. Rats were then subcutaneously injected with VPA (300 mg/kg) or normal saline as control. Blood of 5 rats in each group was with drawn from the abdominal aorta at 6 hours after injury for measurement of plasma creatine kinase-MB (CK-MB) activities; then the rats were sacrificed and heart tissues were harvested for the measurement of acetylated histone H3 and activated caspase-3 by Western Blot. The remaining rats were used for 12-hour survival analysis. Compared with sham-scald group, there was a significant increase in plasma CK-MB activities (5 438.0 ± 413.6 U/L vs. 2 881.0 ± 324.8 U/L, P<0.05) and activated caspase-3 protein levels in heart tissue (gray value: 1.75 ± 0.25 vs. 1.00 ± 0.18, P<0.05) and an significant decline in the acetylation levels of histone H3 (gray value: 0.55 ± 0.18 vs. 1.00 ± 0.20, P<0.05) after major burn injury. VPA treatment significantly reduced the plasma CK-MB activities [(4 018.0 ± 388.3) U/L], activated caspase-3 protein levels in heart tissue (gray value: 1.33 ± 0.20), and raised the acetylation levels of histone H3 (gray value: 2.20 ± 0.23, all P<0.05). Survival analysis by Kaplan-Meier curves showed that the survival was improved after VPA treatment, and the survival rate was increased from 0 to 50% at 12 hours (P<0.05). VPA can attenuate cardiac injury and improve survival in a rodent model of lethal burn injury. These protective effects may be due to its inhibitory effects on histone deacetylase and caspase-3 activation.