title: Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress.
abstract: BACKGROUND
  Animal studies suggest that reactive oxygen species (ROS) play an important role in the development of diabetic cardiomyopathy.
  
  
  OBJECTIVE
  Matrix metalloproteinase-2 (MMP-2) is activated by ROS and contributes to the acute loss of myocardial contractile function by targeting and cleaving susceptible proteins including troponin I (TnI) and alpha-actinin.
  
  
  METHODS
  Using the streptozotocin-induced diabetic rat model, we evaluated the effect of daily in vivo administration of sodium selenate (0.3 mg/kg; DMS group), or a pure omega-3 fish oil with antioxidant vitamin E (omega-3E; 50 mg/kg; DMFA group), which has antioxidant-like effects, for 4 weeks on heart function and on several biochemical parameters related to oxidant stress and MMP-2.
  
  
  RESULTS
  Although both treatments prevented the diabetes-induced depression in left ventricular developed pressure (LVDP) as well as the rates of changes in developed pressure (+/-dP/dt) (P<.001), the improvement in LVDP of the DMS group was greater compared to that of the DMFA group (P<.001). Moreover, these treatments reduced the diabetes-induced increase in myocardial oxidized protein sulfhydryl and nitrite concentrations (P<.001). Gelatin zymography and Western blot data indicated that the diabetes-induced changes in myocardial levels of MMP-2 and tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) and the reduction in TnI and alpha-actinin protein levels were improved in both the DMS and DMFA groups (P<.001).
  
  
  CONCLUSIONS
  These results suggest that diabetes-induced alterations in MMP-2 and TIMP-4 contribute to myocardial contractile dysfunction by targeting TnI and alpha-actinin and that sodium selenate or omega-3E could have therapeutic benefits in diabetic cardiomyopathy.
authors: Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey.
authors: Aslihan
authors: A
authors: Aydemir-Koksoy
authors: Ayca
authors: A
authors: Bilginoglu
authors: Meltem
authors: M
authors: Sariahmetoglu
authors: Richard
authors: R
authors: Schulz
authors: Belma
authors: B
authors: Turan
mesh_terms: D000185:Actinin / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D064586:Selenic Acid; D018036:Selenium Compounds / Q000627:therapeutic use; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D019210:Troponin I / Q000187:drug effects / Q000378:metabolism*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D000185:Actinin; D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D020778:Matrix Metalloproteinase 2; D017382:Reactive Oxygen Species; D064586:Selenic Acid; D018036:Selenium Compounds; D019714:Tissue Inhibitor of Metalloproteinases; D019210:Troponin I; D000097792:Tissue Inhibitor of Metalloproteinase-4