title: Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy.
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.
authors.affiliation: a Department of Pharmacology .
authors.forename: Md Sayeed
authors.initials: MS
authors.lastname: Akhtar
authors.affiliation: a Department of Pharmacology .
authors.forename: Krishna Kolappa
authors.initials: KK
authors.lastname: Pillai
authors.affiliation: a Department of Pharmacology .
authors.forename: Quamrul
authors.initials: Q
authors.lastname: Hassan
authors.affiliation: b Department of Pharmacognosy , and.
authors.forename: Shahid Husain
authors.initials: SH
authors.lastname: Ansari
authors.affiliation: c Department of Pharmaceutics, Faculty of Pharmacy , Jamia Hamdard , New Delhi , India.
authors.forename: Javed
authors.initials: J
authors.lastname: Ali
authors.affiliation: a Department of Pharmacology .
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akhtar
authors.affiliation: a Department of Pharmacology .
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002097:C-Reactive Protein / Q000032:analysis; D002316:Cardiotonic Agents / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D058065:Diabetic Cardiomyopathies / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D005979:Glutathione Peroxidase / Q000378:metabolism; D006835:Hydrazones / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D007004:Hypoglycemic Agents; D007328:Insulin; D011724:Pyridazines; D014409:Tumor Necrosis Factor-alpha; D000077464:Simendan; D008315:Malondialdehyde; D002097:C-Reactive Protein; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; D017257:Ramipril
keywords: Cardiomyopathy; diabetes; levosimendan; mitochondrial damage; oxidative damage; streptozotocin