Mustafa Birincioglu

Effect of estrogen therapy on adipocytokines in ovariectomized-aged rats

Aim:  Obesity is a chronic disease that is characterized by excessive accumulation of body fat. The physiological changes associated with estrogen deprivation in menopause have a significant impact on total body fat and adipose tissue distribution. Adipocytokines, such as adiponectin and leptin are related to adipose tissue, and their levels are affected by estrogen. The aim of the present study was to investigate the alteration of adipocytokine levels with estrogen therapy.

Protective effect of vitamin B5 (dexpanthenol) on cardiovascular damage induced by streptozocin in rats

OBJECTIVES This study investigated whether Dexpanthenol (DEX) improves diabetic cardiovascular function and cardiac performance by regulating total oxidant and antioxidant status. METHODS Diabetes was induced by a single intraperitoneal injection of Streptozocin (50 mg/kg in 1 ml of saline) and treatment groups received DEX (300 mg/kg/day) for 6 weeks. Endothelium (in)dependent relaxation responses were assessed in thoracic aortic rings and coronary vasculature together with alpha receptor and voltage dependant contractile responses of aorta. Myocardial contractility has been recorded by an intra ventricular latex balloon. Total oxidant and antioxidant status were measured from the serum samples. RESULTS Induction of diabetes resulted in an apparent body weight loss, high blood glucose, endothelial dysfunction and increased serum oxidant status. DEX supplementation restored the endothelial dysfunction, antioxidant status and body weight whereas decreasing blood glucose level. CONCLUSION Along with the standard therapy of diabetes, DEX can be used as a safe and economical way of adjuvant therapy to diminish the burden of the disease (Tab. 3, Fig. 3, Ref. 30).

Antidepressant-like effects of the xanthine oxidase enzyme inhibitor allopurinol in rats. A comparison with fluoxetine

Allopurinol is a xanthine oxidase enzyme inhibitor that is widely used for the treatment of hyperuricemia and gout. The activity of tryptophan 2,3-dioxygenase, which metabolizes tryptophan (TRP), is decreased by xanthine oxidase inhibitors, causing TRP levels in the body to be increased. Increases in TRP levels in the brain might have antidepressant effects. The purpose of this study is to evaluate the antidepressant effects of allopurinol compared to those of fluoxetine, which is a proven antidepressant. Thirty-two Wistar albino male rats were divided into four groups (control, 10mg/kg fluoxetine, 50mg/kg allopurinol, 50mg/kg allopurinol+10 mg/kg fluoxetine; n=8 per group), and forced swimming tests were performed before and after 14days of drug administration. Serotonin, 5-hydroxyindolacetic acid and uric acid levels were measured in blood samples after the final treatment. When allopurinol and fluoxetine were administered separately, a decrease in the duration of immobility and an increased duration of swimming were observed in the forced swimming test. The results showed similar antidepressant efficacies between allopurinol and fluoxetine. However, we found no statistically significant difference in the antidepressant effect of the combined therapy versus single drug therapy.

Effects of angiotensin converting enzyme inhibition on adiponectin levels and lipid profile in the ovariectomized-aged rats

Objective: To investigate the relationship between angiotensin converting enzyme (ACE) and adiponectin and lipid profile in the ovariectomized-aged rats. Materials and Methods: Wistar albino rats were first divided into two groups; control (C) and ovariectomized (OVX). Bilateral ovariectomy were carried out on rats (n = 30) except control group (n = 10). After 6 weeks from ovariectomy, ovariectomized rats were subdivided into three groups; one group received no treatment (OVX), two groups received low dose (OVX + Cap5; 5 mg/kg/day) and high dose (OVX + Cap20; 20 mg/kg/day) captopril (Cap). Body weights were monitored weekly. Adiponectin, triglyceride, cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels were measured at the end of the 6 weeks. Results: In the OVX group, body weights increased (P < 0.001). In the OVX + Cap20 group, body weights significantly decreased compared with the OVX group during weeks 5 and 6 (P < 0.05). While adiponectin levels increased in the OVX + Cap5 group (P = 0.014), triglyceride and cholesterol levels decreased in the OVX + Cap20 group (P = 0.016 and P < 0.001, respectively) compared to the OVX group. HDL-C and VLDL-C levels decreased only in OVX + Cap20 group (P < 0.005). Conclusions: ACE inhibitors may be decreasing the ovariectomy-induced weight gain by increasing adiponectin levels, and by affecting lipid profiles. The adipose tissue renin-angiotensin system (RAS) may be playing an important role in the development of adiposity.

Silymarin improves vascular function of aged ovariectomized rats.

Both aging and estrogen depletion lead to endothelial dysfunction, which is the main reason of many cardiovascular diseases. Previous reports have shown that cell protective effect of silymarin (SM) depends on its antioxidant and phytoestrogenic properties. We investigated the effect of SM on vascular stiffness of aged menopausal rats and the involvement of estrogenic activity in this effect. Isolated rat aortas were obtained from 22‐month‐old rats, after 18 months of ovariectomy (OVX) follow‐up. Each ring was incubated in tissue bath either with SM (50 mg/L) and 17β‐estradiol (10 μM, E2) or in the presence of SM/fulvestrant (50 mg/L, 10 μM). Endothelium‐intact rings were precontracted with phenylephrine (0.001–30 μM) or high potassium (40 mM); endothelium‐dependent/independent relaxant responses were obtained using acetylcholine (0.001–30 μM) and sodium nitroprusside (0.0001–3 μM), respectively. While phenylephrine sensitivity was significantly increased in OVX rats, relaxations were significantly less in aged OVX rats compared with young rats. In spite of the presence of estrogen antagonist, immediate SM treatment restored the endothelial function and vascular tone better than estrogen replacement. Additionally, as a complementary and alternative medicine, it does not cause estrogenic side effects when taken acutely. Copyright

Treated effect of silymarin on vascular function of aged rats: Dependant on nitric oxide pathway

Abstract Context: Aging leads to endothelial dysfunction and vascular stiffness which are the main causes of many cardiovascular diseases. Previous reports have shown that the cell protective effect of silymarin (SM) is dependent on its antioxidant properties. Objectives: We investigated the effect of SM on vascular functions of aged rats and the involvement of nitric oxide or cyclooxygenase (COX) activity in this effect. Materials and methods: Isolated rat aortas were obtained from 22-month old rats. Each ring was incubated with SM (50 mg/L), SM/l-nitro-arginine methyl ester (100 μM, l-NAME) or SM/indomethacin (10 μM, INDO) in tissue bath. Three- to four-month-old rats were used as young controls. Endothelium-intact rings were precontracted with α-receptor agonist phenylephrine (0.001–30 µM) or voltage-dependent high potassium (40 mM), endothelium dependent/independent relaxant responses were obtained using acetylcholine (0.001–30 µM) and sodium nitroprusside (0.0001–3 µM), respectively. Results: Aging increased phenylephrine sensitivity (6.45 ± 0.08; 6.88 ± 0.09) and decreased KCl contraction (882 ± 118.4; 499 ± 80.4). SM treatment decreased the Emax of both agents (548 ± 109; 223 ± 48.9). Aging deteriorated acetylcholine relaxation (93.9 ± 2.09; 72.0 ± 2.56) and SM improved the response (86.3 ± 1.90). l-NAME prevented the SM effect whereas INDO was ineffective. Discussion and Conclusion: Immediate SM treatment partially restored endothelial dysfunction and vascular tone in aging. The possible mechanism might not be mediated by prostacyclin or the COX pathway in acute administration; the nitric oxide pathway and calcium antagonistic features of SM relate to its action on the vessel.

Effects of a PPAR-gamma receptor agonist and an angiotensin receptor antagonist on aortic contractile responses to alpha receptor agonists in diabetic and/or hypertensive rats.

Summary Aim The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. Methods Male Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hypertensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose–response curves to phenylephrine (Phe) (10-9–10-5 M) and clonidine (Clo) (10-9–10-5 M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 μM) and/or losartan (10 μM). Results Pioglitazone and losartan caused a shift to the right in contractile response to phenylephrine in all groups. The sensitivity of the aortic rings to phenylephrine was decreased in the presence of pioglitazone and/or losartan in all groups. The contractile response of clonidine decreased in the presence of pioglitazone and/or losartan in the control, HT and DM groups. Conclusion The sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. Concomitant use of PPAR-gamma agonists, thiazolidinediones, and angiotensin receptor blockers may be effective treatment for diabetes and hypertension.

The effect of Hypericum perforatum on isolated rat aorta

Context: Different Hypericum species such as Hypericum perforatum (HP) L. and Hypericum triquetrifolium Turra are well known and widely used traditional medicine in Turkey. Objectives: We investigated the effect of standardized HP extract on endothelium and vascular function. Materials and methods: After suspending the aortas with endothelium in organ baths containing Krebs solution, contractile and relaxant responses were assessed in the absence and presence of HP (0.05 mg/ml). Results: Although there were significant reductions in the contractile responses to phenylephrine (1113.73 ± 164.11; 477.40 ± 39.94; p < 0.05) and potassium chloride (745.58 ± 66.73; 112.58 ± 26.58; p < 0.05), no differences in the relaxant responses to acetylcholine (94.61 ± 2.65; 87.79 ± 9.40) and sodium nitroprusside (108.82 ± 5.06; 106.43 ± 7.45) were observed. Discussion and conclusion: These data suggest that even the high dose of HP intervention does not bring any harmful effect on endothelium and smooth muscle function; meanwhile it might be beneficial on some of diseases accompanied with increased vascular contraction.

Drug exposure in early pregnancy might be related to the effects of increased maternal progesterone in implantation period

Abstract Aim: This short communication aims to evaluate the relation in between drug exposure time and early pregnancy regarding gestational weeks. Methods: The study covers the referrals made to the Department of Pharmacology for a teratogenic consultation in a 3-year period. From the recordings of pregnant women, the last menstrual period and the starting date of medication were used to determine the time of prescription with regard to gestational weeks. Results: In all of the three years, potentially teratogenic medication was prescribed more frequently in the 3rd, 4th and 5th gestational weeks (in between 15–35 days of pregnancy). Approximately 75% of the pregnant women in the study were prescribed with drugs, most frequently with analgesics, antibiotics, gastrointestinal drugs and antidepressants, in these gestational weeks. Conclusions: The timing of prescriptions in early pregnancy frequently coincides with the increased levels of maternal progesterone in implantation period. Progesterone may lead to negative mood symptoms of an increased pain perception, anxiety, irritability and aggression in some of the pregnant women and therefore causes an increased stress condition which in turn may result in pain, infection and inflammation in the individual. Taking the frequently used medications into consideration, the reason for prescriptions in this period might be related to the symptoms originating from the effects of progesterone. Future studies are needed to better demonstrate this association of drug exposure and effects of maternal progesterone in early pregnancy.