Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress.
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.
Aydemir-Koksoy
Aslihan
A
Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey.
Bilginoglu
Ayca
A
Sariahmetoglu
Meltem
M
Schulz
Richard
R
Turan
Belma
B
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
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