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

被引:12
作者
Akhtar, Md Sayeed [1 ]
Pillai, Krishna Kolappa [1 ]
Hassan, Quamrul [1 ]
Ansari, Shahid Husain [2 ]
Ali, Javed [3 ]
Akhtar, Mohammed [1 ]
Najmi, Abul Kalam [1 ]
机构
[1] Jamia Hamdard, Fac Pharm, Dept Pharmacol, New Delhi 110062, India
[2] Jamia Hamdard, Fac Pharm, Dept Pharmacognosy, New Delhi 110062, India
[3] Jamia Hamdard, Fac Pharm, Dept Pharmaceut, New Delhi 110062, India
关键词
Cardiomyopathy; diabetes; levosimendan; mitochondrial damage; oxidative damage; streptozotocin; LOW-DOSE STREPTOZOTOCIN; HEART-FAILURE; RAT; STRESS; CA2+; SYSTEM; ATP;
D O I
10.3109/10641963.2015.1047947
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 ( xxxp<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.
引用
收藏
页码:10 / 22
页数:13
相关论文
共 46 条
[31]  
Nicklas JM, 1999, J CARD FAIL, V5, P18
[32]   Effect of Levosimendan on the Short-Term Clinical Course of Patients With Acutely Decompensated Heart Failure [J].
Packer, Milton ;
Colucci, Wilson ;
Fisher, Lloyd ;
Massie, Barry M. ;
Teerlink, John R. ;
Young, James ;
Padley, Robert J. ;
Thakkar, Roopal ;
Delgado-Herrera, Leticia ;
Salon, Jeffrey ;
Garratt, Chris ;
Huang, Bidan ;
Sarapohja, Toni .
JACC-HEART FAILURE, 2013, 1 (02) :103-111
[33]   NEW TYPE OF CARDIOMYOPATHY ASSOCIATED WITH DIABETIC GLOMERULOSCLEROSIS [J].
RUBLER, S ;
YUCEOGLU, YZ ;
KUMRAL, T ;
GRISHMAN, A ;
BRANWOOD, AW ;
DLUGASH, J .
AMERICAN JOURNAL OF CARDIOLOGY, 1972, 30 (06) :595-&
[34]   ESTIMATION OF TOTAL PROTEIN-BOUND AND NONPROTEIN SULFHYDRYL GROUPS IN TISSUE WITH ELLMANS REAGENT [J].
SEDLAK, J ;
LINDSAY, RH .
ANALYTICAL BIOCHEMISTRY, 1968, 25 (1-3) :192-&
[35]   Triple verses glimepiride plus metformin therapy on cardiovascular risk biomarkers and diabetic cardiornyopathy in insulin resistance type 2 diabetes mellitus rats [J].
Sharma, Ashish Kumar ;
Srinivasan, B. P. .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2009, 38 (05) :433-444
[36]  
Sotnikova R, 2006, GEN PHYSIOL BIOPHYS, V25, P289
[37]  
Tasal A, 2014, MED SCI MONITOR, V20, DOI 10.12659/MSM.889767
[38]   Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study [J].
Thent, Zar Chi ;
Lin, Teoh Seong ;
Das, Srijit ;
Zakaria, Zaiton .
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2012, 2012
[39]  
Trinder P., 1969, ANN CLIN BIOCHEM, V6, P24
[40]   Overexpression of the sarcoplasmic reticulum Ca2+-ATPase improves myocardial contractility in diabetic cardiomyopathy [J].
Trost, SU ;
Belke, DD ;
Bluhm, WF ;
Meyer, M ;
Swanson, E ;
Dillmann, WH .
DIABETES, 2002, 51 (04) :1166-1171