Cardioprotective effects of magnesium valproate in type 2 diabetes mellitus

Eur J Pharmacol. 2014 Apr 5:728:128-34. doi: 10.1016/j.ejphar.2014.01.063. Epub 2014 Feb 11.

Abstract

We have evaluated the effect of magnesium valproate (210 mg/kg/day, p.o.) in type 2 diabetes induced cardiovascular complications induced by streptozotocin (STZ, 90 mg/kg, i.p.) in neonatal wistar rats. Various biochemical, cardiovascular and hemodynamic parameters were measured at the end of 8 weeks of treatment. STZ produced significant hyperglycaemia, hypoinsulinemia and dyslipidemia, which was prevented by magnesium valproate treatment. STZ produced increase in Creatinine Kinase, C-reactive protein and lactate dehydrogenase levels and treatment with magnesium valproate produced reduction in these levels. STZ produced increase in cardiac and LV hypertrophy index, LV/RV ratio, LV collagen deposition and LV cardiomyocyte diameter which were decreased by magnesium valproate treatment. Magnesium valproate also prevented STZ induced hemodynamic alterations and oxidative stress. These results were further supported by histopathological studies in which magnesium valproate showed marked reduction in fibrosis and cardiac fiber disarray. In conclusion, our data suggests that magnesium valproate is beneficial as an anti-diabetic agent in type-2 diabetes mellitus and also prevents its cardiac complications.

Keywords: Cardiovascular complications; HDAC; Magnesium valproate; Type 2 diabetes mellitus.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / therapeutic use*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Fibrosis
  • Hemodynamics / drug effects
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Streptozocin
  • Valproic Acid / administration & dosage
  • Valproic Acid / therapeutic use*

Substances

  • Cardiotonic Agents
  • Streptozocin
  • Valproic Acid