ABSTRACT. Resveratrol (RSV) has a beneficial role in the prevention of diabetes and alleviates some diabetic complications, such as cardiomyopathy. We investigated cyclooxygenase-1 (COX-1), COX-2, nuclear factor κB (NF-κB), matrix metalloproteinase-9 (MMP-9), and sirtuin 1 (SIRT1) mRNA expression levels in heart tissue after RSV treatment in streptozotocin (STZ)-induced diabetic rats. After induction of chronic diabetes with STZ, 10 mg RSV/kg per day was administered to DM and DM+RSV groups for four weeks. At the end of the experiment, all rats were sacrificed and heart tissues were stored at -80°C; mRNA expression levels of COX-1, COX-2, NF-κB, MMP-9, and SIRT1 genes were analyzed with quantitative real-time PCR. We did not find any significant effect of RSV on Effects of resveratrol on diabetic cardiomyopathy MMP-9, COX-1, COX-2, or NF-κB mRNA levels among the groups. However, SIRT1 mRNA levels decreased in the DM group compared to controls and increased in the DM+RSV group when compared to the DM group. SIRT1 is activated by RSV treatment in diabetic heart tissue. Activation of SIRT1 by RSV may lead to a new therapeutic approach for diabetic heart tissue. We conclude that RSV treatment can alleviate heart dysfunction by inhibiton of inflammatory gene expression such as SIRT1.

The loss of cartilage tissue due to trauma, tumour surgery or congenital defects, such as microtia and anotia, is one of the major concerns in head and neck surgery. Recently tissue‐engineering approaches, including gene delivery, have been proposed for the regeneration of cartilage tissue. In this study, primary chondrocytes were genetically modified with plasmid‐encoding bone morphogenetic protein‐7 (BMP‐7) via the commercially available non‐viral Turbofect vector, with the aim of bringing ex vivo transfected chondrocytes to resynthesize BMP‐7 in vitro as they would in vivo. Genetically modified cells were implanted into gelatin–oxidized dextran scaffolds and cartilage tissue formation was investigated in 15 × 15 mm auricular cartilage defects in vivo in 48 New Zealand (NZ) white rabbits for 4 months. The results were evaluated via histology and early gene expression. Early gene expression results indicated a strong effect of exogenous BMP‐7 on matrix synthesis and chondrocyte growth. In addition, histological analysis results exhibited significantly better cartilage healing with BMP‐7‐modified (transfected) cells than in the non‐modified (non‐transfected) group and as well as the control. Copyright © 2012 John Wiley & Sons, Ltd.

Changes in vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), matrix metalloproteinase (MMP)-9, and endothelial nitric oxide synthase (eNOS) mRNA expression profiles and oxidative stress in the eye tissue microenviroment may have important roles in ocular neovascularization and permeability in proliferative diabetic retinopathy. The present study investigated the effects of resveratrol (RSV) treatment on the mRNA expression profile of VEGF, ACE, MMP-9, and eNOS, which are associated with vascular neovascularization, and glutathione, protein carbonyl, and nitrite-nitrate levels, which are markers of oxidative stress in eyes of diabetic rats. Twenty-four Wistar albino male rats were divided into four groups. After diabetes induction with streptozotocin (10 mg/kg/day) RSV was administered to the RSV and diabetes mellitus (DM) + RSV groups for 4 weeks. The mRNA levels were measured by quantitative real-time polymerase chain reaction assay, and biochemical estimations were determined with spectrophotometric assays in eye homogenates. The mRNA expression levels of VEGF, ACE, and MMP-9 were increased in the DM group compared with the control group, and RSV treatment decreased their mRNA levels. Expression of eNOS mRNA was increased in the RSV and DM groups and decreased in the DM + RSV group. Nitrite-nitrate levels and protein carbonyl content were increased and glutathione levels were decreased in the DM group compared with controls. Consequently, these data suggest that RSV suppressed the expression of eNOS, which is actively involved in the inflammation and healing process in chronic diabetes. Although oxidative stress was increased in eye tissue from diabetic rats, mRNA levels of VEGF, MMP-9, and ACE genes associated with vascular remodeling did not change in diabetic eyes.

Cyclooxygenase (COX), which have the isoforms of COX-1 and COX-2, is the key enzyme of prostaglandins biosynthesis. Especially, COX-2 is induced in inflammatory disease such as Diabetes Mellitus (DM). Resveratrol (RSV), a natural antioxidant, has a beneficial role in prevention of inflammatory disease. We investigated the changes of COX-1 and COX-2 mRNA expression and protein level in diabetic rat kidney after RSV treatment. Three months-old, 44 Wistar albino male rats, which were divided into six groups such as control group, sodium citrate buffer (sham control) group, diabetic group (DM), Dimethyl Sulfoxide induced control group, RSV treated sham control group (RSV) and RSV treated diabetic group (DM + RSV) were used for the study. Experimental diabetes was induced by intraperitoneal injection of 55 mg/kg Streptozotocin. After the induction of chronic diabetes 10 mg/kg per day RSV was administered intraperitoneally for 4 weeks. In this study. RSV has no significant effect on COX-1 mRNA expression in diabetic rat kidney (P > 0.05). Immunohistochemical study showed that COX-1 expression was slightly inhibited in RSV group and was not significantly supressed in DM + RSV group. When comparing control and treated groups, there were no significant differences in COX-2 mRNA or protein levels (P > 0.05). In conclusion, our results indicate that resveratrol do not significantly affect COX gene and protein expression. Therefore, different therapy strategies such as combination with other antidiabetic drugs may tried in STZ induced animal model for reducing diabetic symptoms and altering COX-1 and COX-2 mRNA or protein levels.

In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term.