Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 386, Issue 12, pp 1071–1080 | Cite as

Tempol ameliorates cardiac fibrosis in streptozotocin-induced diabetic rats: role of oxidative stress in diabetic cardiomyopathy

  • Ashraf TayeEmail author
  • Mekky M. Abouzied
  • Omar M. M. Mohafez
Original Article


Long-standing diabetes is associated with increased oxidative stress and cardiac fibrosis. This, in turn, contributes to the progression of cardiomyopathy. The present study was sought to investigate whether the free radical scavenger, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) can protect against diabetic cardiomyopathy and to explore the specific underlying mechanism(s) in this setting. Diabetes was induced in rats by a single intraperitoneal injection dose of streptozotocin (50 mg/kg). These animals were treated with tempol (18 mg kg−1 day−1, orally) for 8 weeks. Our results showed significant increases in collagen IV and fibronectin protein levels and a marked decrease in matrix metalloproteinase-2 (MMP-2) activity measured by gelatin-gel zymography alongside elevated cardiac transforming growth factor (TGF)-β level determined using ELISA or immunohistochemistry in cardiac tissues of diabetic rats compared with control. This was accompanied by an increased in the oxidative stress as evidenced by increased reactive oxygen species (ROS) production and decreased antioxidant enzyme capacity along with elevated lactate dehydrogenase (LDH) and creatine kinase (CK-MB) serum levels as compared with the control. Tempol treatment significantly corrected the changes in the cardiac extracellular matrix, TGF-β, ROS or serum LDH, CK-MB levels, and normalized MMP-2 activity along with preservation of cardiac tissues integrity of diabetic rats against damaging responses. Moreover, tempol normalized the elevated systolic blood pressure and improved some cardiac functions in diabetic rats. Collectively, our data suggest a potential protective role of tempol against diabetes-associated cardiac fibrosis in rats via reducing oxidative stress and extracellular matrix remodeling.


Diabetes Cardiac fibrosis Extracelluar matrix TGF-β Streptozotocin 



The authors are grateful to Prof. Adel M. Bakeer, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University for his kind help in performing histopathological studies and interpretation of the results.

Conflict of interest



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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ashraf Taye
    • 1
    Email author
  • Mekky M. Abouzied
    • 2
  • Omar M. M. Mohafez
    • 3
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyMinia UniversityMinyaEgypt
  2. 2.Department of Biochemistry, Faculty of PharmacyMinia UniversityMinyaEgypt
  3. 3.Departments of Biochemistry, Faculty of PharmacyAl-Azhar University, Assiut BranchAssiutEgypt

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