Magnesium valproate ameliorates type 1 diabetes and cardiomyopathy in diabetic rats through estrogen receptors

Abstract

Estrogen is known to exhibit cardioprotective and antihyperlipidemic action. Valproic acid has been shown to upregulate estrogen receptors (ERs) in breast and prostate cancer tissues. No pharmacological evaluations for magnesium valproate (MgV) so far have been done for diabetic cadio-lipidemic complications. Based on the above context, current study was undertaken to evaluate the therapeutic effectiveness of MgV in cardiac complications associated with type-1 diabetes mellitus in rats wherein diabetes was induced by single tail vein injection of streptozotocin (STZ, 45 mg/kg, IV) in female Sprague Dawley rats and treatment of MgV (210 mg/ kg, PO) was given for eight weeks to diabetic animals, after which, various biochemical and cardiac biomarkers, hypertrophic, hemodynamic and histological parameters along with immunohistochemistry of ERs in the left ventricle (LV) were estimated. MgV treatment significantly controlled hyperglycemia and dyslipidemia, reduced elevated cardiac biomarkers and C-reactive protein(CRP), significantly improved hemodynamic functions and increased the rate of pressure development and decay. MgV also significantly reduced left ventricular hypertrophy index and cardiac hypertrophy index, LV wall thickness, LV collagen, cardiomyocyte diameter and prevented the oxidative stress with significant increase in Na+-K+-ATPase activity in LV. Moreover, MgV reversed STZ-induced histological alterations and decreased glycogen content in LV and increased the ERβ expressions in LV as evidenced by immunohistochemistry. The result indicated that MgV prevented disease progression in the early stage of diabetic cardiomyopathy which seems to be mediated by upregulation of estrogen receptors in LV tissue.