Sodium Butyrate Controls Cardiac Hypertrophy in Experimental Models of Rats

The aim of the present research was to study the effect of sodium butyrate (SB) on partial abdominal aorta constriction (PAAC)-induced cardiac hypertrophy and determine its mechanism of action. Healthy Wistar rats were exposed to PAAC for eight weeks. After eight weeks, we carried out hypertrophic and hemodynamic evaluation and measured oxidative stress parameters and mitochondrial DNA concentration. PAAC control animals exhibited cardiac hypertrophy, decreased hemodynamic functions and oxidative stress. Treatment with SB reduced hypertrophic indices, LV wall thickness, LV collagen levels, cardiomyocyte diameter, serum lipid levels and serum cardiac biomarkers. Treatment with SB also improved hemodynamic functions, prevented oxidative stress and increased mitochondrial DNA concentration. Improvement in hypertrophy due to HDAC inhibition was further confirmed by HDAC mRNA expression studies which revealed that SB decreases expression of prohypertrophic HDAC, i.e., HDAC2, without altering the expression of anti-hypertrophic HDAC5. Sodium butyrate produces beneficial effect on cardiac hypertrophy as is evident, specifically from reduction in hypertrophic parameters including collagen levels, improvement in mitochondrial DNA concentration and preservation of LV systolic and diastolic dysfunction. This beneficial effect of sodium butyrate is mediated through downregulation of class I HDACs, specifically HDAC2 without any effect on class II HDAC, i.e., HDAC5. Thus, selective class I HDAC inhibition is required for controlling cardiac hypertrophy. Newer HDAC inhibitors which are class I inhibitor and class II promoter can be designed to obtain a 'pan' or 'dual' natural HDAC 'regulators.'