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Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of
Aslihan Aydemir-Koksoy1, Ayca Bilginoglu, Meltem Sariahmetoglu
1Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey.
Background:
Animal studies suggest that reactive oxygen species (ROS) play an important role in the development of diabetic cardiomyopathy.
Hypothesis:
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.
Insights
Sodium selenate and omega-3 fish oil with vitamin E show therapeutic potential for diabetic cardiomyopathy by improving heart function and reducing oxidative stress. Both treatments helped preserve key proteins targeted by matrix metalloproteinase-2 (MMP-2).
Area of Science:
- Cardiovascular Research
- Biochemistry
- Pharmacology
Background:
- Diabetic cardiomyopathy is linked to reactive oxygen species (ROS).
- ROS activate matrix metalloproteinase-2 (MMP-2), impairing heart function by degrading proteins like troponin I (TnI) and alpha-actinin.
Purpose of the Study:
- To investigate the therapeutic effects of sodium selenate and an omega-3 fish oil with vitamin E (omega-3E) on diabetic cardiomyopathy in a rat model.
- To assess the impact of these treatments on cardiac function, oxidative stress, and MMP-2 activity.
Main Methods:
- Streptozotocin-induced diabetic rats were treated daily for 4 weeks with sodium selenate (DMS group) or omega-3E (DMFA group).
- Cardiac function (left ventricular developed pressure, +/-dP/dt), myocardial oxidative stress markers, and MMP-2 levels were evaluated.
Main Results:
- Both sodium selenate and omega-3E improved cardiac function and reduced oxidative stress markers in diabetic rats.
- Sodium selenate showed a greater improvement in left ventricular developed pressure compared to omega-3E.
- Both treatments normalized myocardial MMP-2 levels and restored TnI and alpha-actinin protein levels.
Conclusions:
- Diabetes-induced alterations in MMP-2 and TIMP-4 contribute to myocardial contractile dysfunction.
- Sodium selenate and omega-3E demonstrate therapeutic potential for managing diabetic cardiomyopathy by mitigating oxidative stress and protecting cardiac proteins.
