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Targeting apoptosis in the heart of streptozotocin-induced diabetic rats
1Clinical Pharmacology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt. mnhbaraka@yahoo.com
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.
Insights
Diabetic cardiomyopathy involves cardiomyocyte apoptosis. PPAR agonists, fenofibrate and rosiglitazone, show protective effects by reducing apoptosis and improving heart function in diabetic rats.
Area of Science:
- Cardiovascular Research
- Metabolic Diseases
- Pharmacology
Background:
- Diabetic cardiomyopathy is a complex condition linked to diabetes mellitus.
- Cardiomyocyte apoptosis is a potential contributing factor to diabetic cardiomyopathy's development.
- Peroxisome proliferator-activated receptors (PPARs) are implicated in metabolic regulation and inflammation.
Purpose of the Study:
- To investigate the role of cardiomyocyte apoptosis in diabetic cardiomyopathy.
- To evaluate the efficacy of PPAR-alpha (fenofibrate) and PPAR-gamma (rosiglitazone) agonists in suppressing apoptosis and ameliorating diabetic cardiomyopathy.
Main Methods:
- The study utilized a rat model of streptozotocin-induced diabetes.
- Diabetic rats were treated with either fenofibrate (PPAR-alpha agonist) or rosiglitazone (PPAR-gamma agonist) for 12 weeks.
- Control groups included normal rats and untreated diabetic rats.
Main Results:
- Both PPAR-alpha and PPAR-gamma agonists significantly reduced left ventricular to body weight ratio.
- Treatment with agonists decreased markers of apoptosis (caspase-3), inflammation (tumor necrosis factor-alpha), fibrosis (hydroxyproline), and lipid accumulation (FFAs, TGs).
- Oxidative stress parameters were improved, and left ventricular developed tension was enhanced in treated groups.
Conclusions:
- Apoptosis plays a significant role in the pathophysiology of diabetic cardiomyopathy.
- PPAR-alpha and PPAR-gamma agonists demonstrate a protective effect against diabetic cardiomyopathy.
- Fenofibrate and rosiglitazone represent potential therapeutic strategies for managing diabetic cardiomyopathy.
