Targeting apoptosis in the heart of streptozotocin-induced diabetic rats.
OBJECTIVE
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.
Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. mnhbaraka@yahoo.com
Azza
A
Baraka
Hala
H
AbdelGawad
D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D048909:Diabetes Complications / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D011345:Fenofibrate / Q000494:pharmacology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D051381:Rats; D000077154:Rosiglitazone; D013311:Streptozocin; D045162:Thiazolidinediones / Q000494:pharmacology
D000960:Hypolipidemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013311:Streptozocin; D011345:Fenofibrate