الفهرس 
contentsOnly 14 pages are availabe for public view
 |  | from | 36 |  |  |
| | | from | 36 | | |
Abstract
The prevalence of the diabetic heart has markedly increased in the past few years and is now considered the main cause of sickness and death among the diabetic and obese population. Diabetic cardiomyopathy is associated with increased oxidative stress that stimulates cellular injury and contributes to the development and progression of complications associated with diabetes.
To date, no studies regarding the effect of punicalagin on diabetic cardiac apoptosis and injury have been conducted. The present study hypothesized that punicalagin can counteract oxidative stress and, in turn, ameliorate cellular damage and reduce the development and progression of diabetic complications in the heart. Therefore, the current study was designed to investigate the potential beneficial effect of punicalagin against diabetes-induced cardiac injury and apoptosis in connection with its anti-lipid peroxidation and anti-hyperlipidemia actions include, serum glucose, insulin, and HOMA-IR; blood HbA1C, serum lipid profile. Heart function was estimated by measuring the levels of troponin T, CK-MB and LDH in serum. Oxidative stress was evaluated by estimating MDA and H2O2 contents as well as the levels of SOD, CAT and GSH in the heart. Pro-inflammatory parameters including IL-1β, IL-6 and TNF-α were determined in serum. The molecular parameters include apoptosis, CD95, Bcl-2, Bax, P53 and caspases,3,8, &9 were estimated in the heart. DNA damage in heart samples was assessed using the single-cell gel electrophoresis (comet assay) method. Histopathological examination was performed on the heart apex.
Results:The treatment with PU of diabetic rats for two weeks showed a significant maintenance and prevented loss of weight when compared with the diabetic group. The treatment of diabetic rats with PU led to a significant improvement and revealed a significant lower in the blood glucose levels and HbA-1c percent than the diabetic rats during the experimental period. Moreover, the treatment with PU of diabetic rats for two weeks significantly maintained insulin level within control values and demonstrated higher levels when compared with STZ-treated group. The treatment with PU every other day for 15 days after STZ injection showed a significant decrease in HOMA-IR values compared with that of the STZ-treated rats. The treatment with PU of diabetic animals significantly controlled the elevation in these lipid fractions after the induction of diabetes and demonstrated values comparable with the control group. In contrast, the high-density lipoprotein level of the STZ-treated rats was significantly lower than normal control, and the treatment with PU showed significantly higher level compared to diabetic group. The administration of PU after diabetic induction resulted in a significant decrease in the level of troponin T and the activities of CK-MB and LDH compared with diabetic rats and displayed insignificant changes compared with the normal control group.
The administration of PU in diabetic group caused a significant decrease in H2O2 and MDA levels compared to STZ-treated group. Moreover, H2O2 concentration in PU group is significantly lower than that in the normal control.The treatment of diabetic rats with PU produced a significant improvement and demonstrated increased levels of SOD, CAT and GSH in heart compared with diabetic group. GSH content is significantly higher in in the PU group than that in the normal group.The treatment with PU of diabetic rats caused in remarkable improvements and exhibited a significant decrease in IL-1β, IL-6 and TNF-α when compared with the diabetic rats group. The treatment of diabetic rats with PU significantly reduced the number of apoptotic and necrotic cells compared to the diabetic rats. Moreover, The administration of PU into the STZ-treated rats led to a marked increase in the live cells as compared to diabetic treated rat. The administration of PU considerably blunted the deviations in the expression of Bcl-2 and Bax. The administration of PU significantly controlled the diabetes-induced expression of caspases 3,8, &9. The treatment with PU for the diabetic group showed a significant improvement in the level of CD95 and demonstrated a decrease when compared with STZ treated group. The treatment with PU after diabetic induction showed a markedly improvement in the proportion of protein P53 and demonstrated a decrease compared to diabetic rats. The treatment of diabetic rats with PU significantly repressed the increase of comet parameters indicating the protective effects of PU on STZ-induced DNA damage. Punicalagin treatment of STZ-induced diabetic rats reduced these changes in the STZ-injected rat hearts and revealed markedly less disorganization of the architecture of most of the cardiac muscle fibers, with centrally located vesicular nuclei.In conclusion, this is the first study to demonstrate that punicalagin protects against STZ-induced diabetic cardiomyopathy in rats. The underlying mechanisms are pleiotropic and include anti-hyperglycemic, anti-hyperlipidemic, antioxidant and anti-inflammatory activities. This polyphenol phytocompound can play an important role in the modulation of inflammatory and apoptotic cell signaling in the diabetic heart.