Is the effect of melatonin on vascular endothelial growth factor receptor-2 associated with angiogenesis in the rat ovary?

OBJECTIVES: Vascular endothelial growth factor (VEGF) and its receptors play important roles in angiogenesis. Melatonin plays an important role in gonadal development; thus, its effect on the reproductive system is evident. We investigated the influence of melatonin on the expression of VEGF, vascular endothelial growth factor receptor-1 (VEGFR1) and vascular endothelial growth factor receptor-2 (VEGFR2), as well as on changes in oxidative stress markers and follicle numbers in rat ovaries. METHODS: For this purpose, 45 Wistar rats were separated into the following groups: Group 1, control; Group 2, vehicle; and Group 3, melatonin. Rats in Group 3 were treated with melatonin at 50 mg/kg/day for 30 days. The effects of melatonin on the expression of VEGF, VEGFR1 and VEGFR2 were established by immunohistochemistry analysis. The effects of melatonin on antioxidant enzyme activities were demonstrated by spectrophotometric analysis. RESULTS: Based on immunohistochemistry analysis, VEGFR2 was predominantly localized to theca cells in the ovary. Our data indicate that melatonin treatment can significantly increase VEGF and VEGFR1 expression in the ovary ( p <0.05). Additionally, the number of degenerated follicles significantly decreased with melatonin treatment ( p <0.05). Melatonin administration also led to significant increases in antioxidant enzyme levels in the ovary. CONCLUSION: Melatonin treatment exerts protective effects on follicles against increased lipid peroxidation through modulating tissue antioxidant enzyme levels. These effects may be related to angiogenesis and antioxidant activities.

Melatonin protects against streptozotocin-induced diabetic cardiomyopathy through the mammalian target of rapamycin (mTOR) signaling pathway.

BACKGROUND: Several studies demonstrated that the overexpression of mammalian target of rapamycin (mTOR) signaling protein is associated with cardiomyopathy. However, the effect of mTOR on the heart in hyperglycemic condition is still controversial. OBJECTIVES: We aimed to investigate the expression of mTOR and antioxidant enzyme activity in cardiac hypertrophy in rats with streptozotocin-induced diabetes mellitus (DM), and the effects of the melatonin on diabetic cardiomyopathy (DCM). MATERIAL AND METHODS: Forty male Wistar rats were used as the experimental animals. The rats were divided into 4 groups (10 animals in each): group 1 (control group), group 2 (ethanol vehicle group), group 3 (iatrogenically DM-induced group), and group 4 (group given melatonin after iatrogenical DM induction). Streptozotocin was injected intraperitoneally to group 3 and 4 to induce experimental type 1 DM. Melatonin was injected intraperitoneally at a dose of 50 mg/kg/day for 56 days to group 4. We investigated expression of mTOR levels in heart muscle fibers of all groups. Laboratory analysis and transthoracic echocardiography were performed. RESULTS: Melatonin increased the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), which were reduced due to hyperglycemia. The mTOR expression levels were significantly higher in group 3 (DM group) compared with controls, whereas melatonin treatment significantly decreased the levels of mTOR expression in group 4 (melatonin + DM group). Diabetic rats developed myocardial hypertrophy with preserved cardiac function. CONCLUSIONS: Cardioprotective effect of melatonin may reduce damages caused by DM in the heart muscle fibers through the mTOR signaling pathway.

Is the effect of melatonin on vascular endothelial growth factor receptor-2 associated with angiogenesis in the rat ovary?

OBJECTIVES Vascular endothelial growth factor (VEGF) and its receptors play important roles in angiogenesis. Melatonin plays an important role in gonadal development; thus, its effect on the reproductive system is evident. We investigated the influence of melatonin on the expression of VEGF, vascular endothelial growth factor receptor-1 (VEGFR1) and vascular endothelial growth factor receptor-2 (VEGFR2), as well as on changes in oxidative stress markers and follicle numbers in rat ovaries. METHODS For this purpose, 45 Wistar rats were separated into the following groups: Group 1, control; Group 2, vehicle; and Group 3, melatonin. Rats in Group 3 were treated with melatonin at 50 mg/kg/day for 30 days. The effects of melatonin on the expression of VEGF, VEGFR1 and VEGFR2 were established by immunohistochemistry analysis. The effects of melatonin on antioxidant enzyme activities were demonstrated by spectrophotometric analysis. RESULTS Based on immunohistochemistry analysis, VEGFR2 was predominantly localized to theca cells in the ovary. Our data indicate that melatonin treatment can significantly increase VEGF and VEGFR1 expression in the ovary ( p <0.05). Additionally, the number of degenerated follicles significantly decreased with melatonin treatment ( p <0.05). Melatonin administration also led to significant increases in antioxidant enzyme levels in the ovary. CONCLUSION Melatonin treatment exerts protective effects on follicles against increased lipid peroxidation through modulating tissue antioxidant enzyme levels. These effects may be related to angiogenesis and antioxidant activities.

Effect of Melatonin on the Expression of VEGF-A and on the Degeneration of Follicle Reserve in Rat Ovary.

OBJECTIVE: To analyze the effects of melatonin on vascular endothelial growth factor A (VEGF-A) expression and follicle reserve in rat ovary. MATERIALS AND METHODS: A total of 45 female Wistar rats were used in the present study. Rats were divided into three groups: group 1 (control), group 2 (vehicle), and group 3 (melatonin). Rats in the melatonin group were treated with an intraperitoneal injection of melatonin at a dose of 50 mg/kg/day for 56 days. We investigated VEGF-A expression in rat ovary in all the groups using Western blot and reverse transcription-polymerase chain reaction. Histopathological parameters were evaluated using light microscopy. RESULTS: The number of atretic follicles was significantly lower in the melatonin treatment rats than in the control rats (p<0.05); however, the number of antral follicles was significantly higher in the former (p<0.05). Additionally, we observed a weak immunoblot stain in the melatonin group for VEGF-A protein. Interestingly, melatonin treatment induced a significant decrease in VEGF-A expression in the ovary of group 3 rats (p<0.05), whereas no such difference was observed between group 1 and group 2 rats (p>0.05). CONCLUSION: The present study demonstrates that the protective effect of melatonin on the degeneration of follicles in rat ovary is reduced by decreasing the VEGF-A expression. These results suggest that melatonin is effective against follicular atresia and preserves antral follicles, thus, offering a therapeutic advantage in clinical use.

Compliance With Dyslipidemia Guidelines in Daily Practice: How Effective Is Cardiovascular Risk Prevention?

PURPOSE: Cardiovascular disease (CVD) due to atherosclerosis is the leading cause of early mortality and morbidity. The current European guidelines on CVD prevention in clinical practice recommend the use of the Systematic Coronary Risk Estimation (SCORE) system. The current American Heart Association guidelines recommend the use of the new pooled cohort risk assessment equations to estimate the 10-year atherosclerotic CVD risk. The purpose of this article was to investigate the compliance of dyslipidemia guidelines in daily practice in patients with dyslipidemia or who have risk factors for CVD. METHODS: The study group consisted of 500 outpatients who had dyslipidemia or risk factors for CVD. The risk level was computed according to the European and American Heart Association guidelines. Therapeutic LDL-C targets were identified based on the calculated risk level. Therapeutic target levels were compared based on the dosage of statins used and achievement of the LDL-C goal in daily practice according to the risk levels. FINDINGS: According to the European dyslipidemia guidelines, 231 patients were in the very-high/high-risk group, and 106 patients (45.9%) achieved the LDL-C target (<100 mg/dL); 210 patients were in the moderate-risk group, and 156 (74.3%) patients achieved the LDL-C target (<115 mg/dL); and 59 patients were in the low-risk group, and 55 (93.2%) patients achieved the LDL-C target (<155 mg/dL). Univariate and multivariate logistic regression analyses revealed that the LDL-C level and presence of coronary artery disease were significantly reverse associated with achievement of the LDL-C goal (both, P < 0.001). IMPLICATIONS: Our results showed that the majority of patients were in the very-high/high-risk group in daily practice. Although the European dyslipidemia guidelines are more likely to be used in daily practice, achievement of the guidelines-recommended treatment goals was low.

Development of massive pulmonary embolism during echocardiographic imaging: A case report.

RATIONALE: Pulmonary embolism (PE) is a common diagnostic consideration for patients who present to the emergency department (ED) with chest pain, dyspnea, or both. In addition, PE has a very high mortality in patients who are hemodynamically unstable. An electrocardiography, bedside transthoracic echocardiogram, and computed tomography pulmonary angiogram are usually performed to confirm the diagnosis. PATIENT CONCERNS: A 53-year-old man was admitted to the cardiology clinic with complaints of dyspnea, chest pain, and general weakness after walking. He had a history of hypertension and smoking. DIAGNOSIS: During synchronous recording of echocardiographic images, a large mobile thrombus detached from the right atrium, and first embolized to the right ventricle and then to the main pulmonary artery from the right heart chambers. Soon after, shortness of breath developed which clinically worsened the patient. Transthoracic echocardiogram which demonstrated the thrombus in the pulmonary artery or right heart chambers was suspected of causing acute massive PE. INTERVENTIONS: The patient was transferred to Critical Care Unit for monitoring; 100 mg of alteplase was initiated immediately and alleviated the hemodynamic instability within 2 hours of intravenous administration. OUTCOMES: To the best of our knowledge, this is the first synchronous echocardiographic recording showing the embolization of a thrombus from the right atrium, first to the right ventricle and then to the main pulmonary artery. LESSONS: Transthoracic echocardiography provides a safe, rapid, and noninvasive diagnostic tool for evaluation of suspected massive PE. Thrombolytic therapy is useful for treating acute massive PE that leads to hemodynamic instability.