Potential of Sodium Valproate to Mitigate Cardiac Damage in Severe Burn Injury: Insights into Apoptosis and HIF-1α Inhibition

Abstract

Severe burn injuries often lead to significant cardiac damage, manifesting in impaired cardiac function, myocardial injury, and subsequent long-term complications. This study investigates the potential of sodium valproate (VPA) as a therapeutic agent to mitigate cardiac damage in a rat model of severe burn injury. The primary objectives were to assess the effects of VPA on cardiac function, apoptosis, hypoxia-inducible factor 1-alpha (HIF-1α) expression, and inflammatory and oxidative stress responses. Rats were divided into five groups: control (distilled water), and four treatment groups receiving different concentrations of sodium valproate (1%, 2%, 5%, and 10%) after burn injury. Cardiac function was evaluated through echocardiographic parameters, including left ventricular ejection fraction (LVEF), stroke volume (SV), and cardiac output (CO). Histopathological analysis, TUNEL assay for apoptosis, and Western blot for HIF-1α expression were conducted to assess myocardial injury and molecular responses. Inflammatory and oxidative stress markers, including TNF-α, IL-6, MDA, and SOD, were also measured. Results showed that sodium valproate significantly improved cardiac function, reduced myocardial injury, and decreased apoptosis, especially in the 10% VPA treatment group. VPA also inhibited the upregulation of HIF-1α and reduced inflammation and oxidative stress, as evidenced by lower levels of TNF-α, IL-6, MDA, and higher SOD activity. These findings suggest that sodium valproate has cardioprotective effects following severe burn injury, likely through its ability to modulate apoptosis, HIF-1α expression, and inflammatory and oxidative stress responses. Sodium valproate presents a promising therapeutic approach for mitigating burn-induced cardiac damage, warranting further clinical investigation to determine its potential role in burn care management.