Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy

Clin Exp Hypertens. 2016;38(1):10-22. doi: 10.3109/10641963.2015.1047947. Epub 2015 Jul 24.

Abstract

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25 mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia ((§§§)p < 0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.

Keywords: Cardiomyopathy; diabetes; levosimendan; mitochondrial damage; oxidative damage; streptozotocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • C-Reactive Protein / analysis
  • Cardiotonic Agents / pharmacology
  • Caspase 3 / metabolism
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetic Cardiomyopathies* / metabolism
  • Diabetic Cardiomyopathies* / physiopathology
  • Diabetic Cardiomyopathies* / prevention & control
  • Glutathione Peroxidase / metabolism
  • Hydrazones / pharmacology*
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin / pharmacology
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects*
  • Pyridazines / pharmacology*
  • Ramipril / pharmacology*
  • Rats
  • Rats, Wistar
  • Simendan
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cardiotonic Agents
  • Hydrazones
  • Hypoglycemic Agents
  • Insulin
  • Pyridazines
  • Tumor Necrosis Factor-alpha
  • Simendan
  • Malondialdehyde
  • C-Reactive Protein
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Caspase 3
  • Ramipril