Key result
Treatment with PPAR-alpha and -gamma agonists decreased left ventricular to body weight ratio, apoptotic and inflammatory markers, and improved oxidative stress in diabetic rats.
Why the study?
Do PPAR-alpha or PPAR-gamma agonists reduce cardiomyocyte apoptosis and improve diabetic cardiomyopathy in streptozotocin-induced diabetic rats?
Do PPAR-alpha or PPAR-gamma agonists reduce cardiomyocyte apoptosis and improve diabetic cardiomyopathy in streptozotocin-induced diabetic rats?
PPAR-alpha and -gamma agonists may protect against diabetic cardiomyopathy by suppressing cardiomyocyte apoptosis.
Supports PPAR agonists in diabetic rat cardiomyopathy models; leaves open translation to human disease.
OBJECTIVES: The aim of the current study was to address the issue of cardiomyocyte apoptosis as a possible contributor in the development of diabetic cardiomyopathy and whether it would be possible to suppress this apoptosis by the use of a peroxisome proliferator-activated receptor (PPAR)-alpha agonist (fenofibrate) or a PPAR-gamma agonist (rosiglitazone). METHODS: Ten normal male albino rats (group I) were injected intraperitoneally (IP) by a single dose of saline and served as a control for group II. Thirty male albino rats were made diabetic by IP streptozotocin (STZ) injection and were divided into 3 groups: group II (nontreated diabetic rats), groups III and IV (diabetic rats treated with PPAR-gamma agonist (rosiglitazone), and PPAR-alpha agonist (fenofibrate) respectively, for 12 weeks starting 1 week following STZ injection. RESULTS: The studied drugs decreased left ventricular to body weight ratio and cardiac: caspase-3, tumor necrosis factor-alpha, hydroxyproline, free fatty acids (FFAs) as well as triglycerides (TGs) and improved oxidative stress parameters as well as left ventricular papillary muscle developed tension (DT). CONCLUSIONS: The results of the current study support the hypothesis that apoptosis plays a key role in the pathophysiology of diabetic cardiomyopathy and demonstrate that the use of PPAR-alpha and -gamma agonists might have a protective role against diabetic cardiomyopathy.
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Baraka et al. (2010) studied Diabetic cardiomyopathy (n=40). PPAR-gamma agonist (rosiglitazone) and PPAR-alpha agonist (fenofibrate) vs. Nontreated diabetic rats and normal rats was evaluated on Left ventricular to body weight ratio, cardiac caspase-3, TNF-alpha, hydroxyproline, FFAs, TGs, oxidative stress, and LV papillary muscle developed tension. Treatment with PPAR-alpha and -gamma agonists decreased left ventricular to body weight ratio, apoptotic and inflammatory markers, and improved oxidative stress in diabetic rats.
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