ABSTRACT
Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ) combined with high fat diet (HFD) in rats. Methods: Male Wistar rats (150-200 g) were injected with low-dose STZ (45 mg/kg, i.v., single dose) and orally fed with a HFD (20 g/day/rat) for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o.) for a period of 21 days (from 8th day to 28th day). On 29th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH) levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI) and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC) and triglycerides (TGs), apoliproprotein-B glycosylated haemoglobin (HbA1c) levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C) and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.
ABSTRACT
Nitric oxide (NO), a potencially toxic radical, is generally regarded as a multi-potent molecule to be implicated in a wide range of biological function. The presence of nitric oxide synthase(NOS) in the retina, the constitutive isoform in photoreceptor outer segments and and the inducible form in retinal pigment epithelial (RPE) cells, has been demonstrated. The effect of NO in retina has been studying mainly as neurotransmitter. Present study was undertaken to find the role of NO in cultured bovine retinal pigment epithelial cells. Cultured bovine retinal pigment epithelial cells were treated with various concentrations of NO generator, S-nitroso-N-acetyl-D, L-penicillamine (SNAP). The survival fractions were measured by MTT assay. The morphologic changes were observed with inverted phase contrast microscope and electron microscope. To evaluate the characteristics of cell death, cells were lysed for DNA extraction, and the agarose gel electrophoresis was done. NO brought a decrease in the survival fraction of cultured bovine retinal pigment epithelial cells as concentrations increased. At high concentrations, cells became sparse. Electron microscopic study showed destruction of nuclear membrane and chromatin condensation in 1 mM SNAP treated group. These findings were compatible with apoptotic cell death that was supported with DNA laddering pattern in agarose gel electrophoresis. NO can induce damage to retinal pigment epithelial cells, and damaged cells are destined to apoptotic cell death.