Resveratrol Protects and Restores Endothelium-Dependent Relaxation in Hypercholesterolemic Rabbit Corpus Cavernosum.

INTRODUCTION: Oxidative stress dependent-decrease in nitric oxide (NO) bioavailability plays an integral role in hypercholesterolemia-induced erectile dysfunction (ED). Resveratrol has been demonstrated to exert beneficial effects against oxidative stress and improve NO bioavailability. AIM: The protective and restorative potentials of resveratrol on endothelium-dependent relaxations were evaluated in hypercholesterolemic rabbit corpus cavernosum (CC). METHODS: Hypercholesterolemia was induced by administering 2% cholesterol diet (CD) (w/w) to the rabbits for 6 weeks. Two different protocols were applied to test the effects of resveratrol on hypercholesterolemia-induced ED. In Protocol-1 (P1), resveratrol was administrated to the rabbits simultaneously with CD in order to evaluate the protective effect, and for Protocol-2 (P2), resveratrol was administrated for 6 weeks after termination of CD in order to evaluate the restorative effect. MAIN OUTCOME MEASURES: Endothelium-dependent relaxations of CC were evaluated by using organ bath studies. In order to elucidate the possible molecular mechanisms, we measured endothelial NO synthase (eNOS) and phosphovasodilator-stimulated phosphoprotein (VASP) expressions and activations, NADPH oxidase, superoxide dismutase (SOD), and catalase (CAT) and glutathione peroxidase (GPx) activity in cavernosal tissues obtained at the end of the study. RESULTS: Resveratrol showed an improvement in the endothelium-dependent relaxation responses in vitro. We demonstrated significantly increased activatory-phosphorylation (p[S1177]-eNOS) and activated phosphovasodilator-stimulated phosphoprotein (phospho-VASP) levels, but reduced phosphorylation (p[T495]-eNOS) of eNOS and NADPH oxidase activity in the resveratrol-administered HC animals compared with hypercholesterolemic control rabbits in the P1. In the P2, resveratrol exhibited an improvement in endothelium-dependent relaxation responses and more pronounced effects on eNOS activation. CONCLUSION: Resveratrol administration, either simultaneously with HC diet or after HC, caused an improvement in the endothelium-dependent relaxation responses in the CC, suggesting its potential in both protective and restorative purposes in hypercholesterolemic rabbit CC.

A study on the protective activity of kefir against gastric ulcer.

BACKGROUND/AIMS: The effect of kefir on peptic ulcer disease was evaluated in an experimental model, with non-steroid anti-inflammatory drugs, together with the determination of gastric mucus secretion by quantitative digital histochemistry. MATERIALS AND METHODS: The experimental group included 28 male albino Wistar rats. After a diet with standard rat bait for 7 days, 14 rats were fed with kefir for 7 days while the others were kept on the same diet. At the 14th day, indomethacin was injected to 7 of the rats fed on kefir and to 7 of the rats on standard rat bait. All the rats were sacrificed after 4 hours. Gastric erosion and ulceration were scored histopathologically. Mucosal mucus was quantified by image analysis, and periodic acid-Schiff stained area percentage was determined. RESULTS: Erosion and ulceration were identified only in cases that received indomethacin. In the cases on kefir, erosion was identified in 6 cases (86%) and ulceration in 1 case. Rats fed on standard diet had erosion in 4 cases (57%) and ulceration in 3 (43%), but the difference was statistically insignificant (Mann-Whitney test, p=0.25). The stained area percentage for gastric mucus was not different between the four groups (Kruskal-Wallis test, p=0.313). CONCLUSIONS: These findings suggest that kefir does not change gastric mucus secretion. Although statistically insignificant, as there were more cases with ulceration in cases on the rat diet, kefir might have a beneficial effect on peptic ulcer disease induced by non-steroid anti-inflammatory drug. This requires further evaluation in larger series.

The effects of non-selective and cyclooxygenase-2-selective non-steroidal anti-inflammatory drugs on heterotopic ossification in rats.

BACKGROUND: Review of the literature revealed several experimental studies on the effects of selective COX-2 inhibitors on fracture healing, but no reports were encountered regarding the effects of these compounds on experimental heterotopic bone formation, so the present study was conducted. MATERIAL/METHODS: Thirty adult male Wistar rats were divided into three groups of ten animals each. Tibial and femoral bones were collected from the rats, cleaned and demineralized, and diaphyseal parts were implanted in muscle pouches created in the right gluteal region, one into each rat. Group 1 received DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), a highly selective COX-2 inhibitor, at a dose of 1.1 mg/kg/day. Group 2 received 2 mg/kg/day of indomethacin. The drugs were administered by oral gavage with 0.5% methyl cellulose as a delivery vehicle for eleven days, beginning on the first postoperative day. Group 3 received only methyl cellulose. RESULTS: Thirty days after the implantation of the demineralized bone matrix, 6/10 of DFU-treated, 9/9 of the indomethacin-treated, and 8/9 of the control rats displayed new bone formation. CONCLUSIONS: The results of this study suggest that no form of non-steroidal anti-inflammatory drug has inhibitory effects on heterotopic bone formation in rats. In our opinion, bone formation is a quite complex process that requires several events and is regulated by several factors, so further investigations other than those using non-steroidal anti-inflammatory drugs are required.