Suat Tekin

The effects of intracerebroventricular infusion of apelin-13 on reproductive function in male rats

Apelin is a novel bioactive peptide as the endogenous ligand for APJ. Apelin and APJ have also been identified in the testis, hypothalamic nuclei such as arcuate, supraoptic and paraventricular nuclei, implicating roles in the control of reproduction. Therefore, the present study was designed to investigate the effects of chronic central infusion of apelin-13 on LH, FSH and testosterone levels and testis morphology. 21 Wistar-Albino male rats received continuous intracerebroventricular infusion via Alzet osmotic mini pumps filled artificial cerebrospinal fluid (vehicle) or apelin-13 at concentrations of 1 or 10 nmol (10 μl/h) for seven days. At the last 90 min of the infusion period, the blood samples were collected at 15 min intervals (0-90 min) for LH and FSH analyses. At the last sampling point, the blood samples were analyzed for testosterone levels. Infusion of high dose apelin-13 significantly suppressed LH release compared with the vehicle values at 30, 60 and 75 min (p<0.05). However, FSH levels did not significantly differ among the groups. Serum testosterone levels in high dose apelin-13 group were statistically lower than the control group (p<0.05). In addition, histological examination showed that infusion of high dose apelin-13 significantly decreased the number of Leydig cells compared with the control and lower dose apelin-13 groups (p<0.05, p<0.01). Our results suggest that apelin-13 may play a role in the central regulation and decreases testosterone release by suppressing LH secretion. Thus, antagonists of the apelin receptor may, therefore, be useful for pharmaceuticals in the treatment of infertility.

Effects of central irisin administration on the uncoupling proteins in rat brain

Irisin is a thermogenic peptide that enables the development of brown adipose tissue from white adipose tissue by activating the UCP1. This study has been designed to determine the effects of the irisin on UCPs. Sprague Dawley female rats were used in the study. 1, 3 and 10μM concentrations of irisin were injected intracerebroventricularly to the rats, and the control group was received only vehicle. The animals were killed at the 16, 24, and 48h time intervals and their brains were taken out. The hypothalamus, pituitary gland, hippocampus, cerebellum, striatum and cortex areas were separated and the UCP2, UCP3, UCP4 and UCP5 mRNA levels were determined. Just before the animals were killed, their body temperatures were recorded. It was observed that after application of the high dose irisin, UCP5 mRNA level in the all brain areas increased (p<0.05); it was also observed that the three doses decreased the UCP4 expression in all brain areas (except the pituitary gland; p<0.05). The UCP2 and UCP3 mRNA expressions showed significantly increase in cerebellum and striatum (p<0.05). The UCP2 mRNA expression decreased in hypothalamus, pituitary gland, hippocampus and cortex areas (p<0.05). It was also observed that the body temperatures of the rats increased depending on the irisin injection and this increase was the most considerable at the 24h (p<0.05). The results of this study suggest that the UCP2-5 is expressed in different areas of the brain, and the irisin affects this expression, and may have effective roles in some brain functions.

Effects of Perineural Administration of Dexmedetomidine in Combination with Levobupivacaine in a Rat Sciatic Nerve Block

Objective The aim of this study was to assess if perineural administration of dexmedetomidine combined with levobupivacaine increases the duration of the sensory and motor blockade of a sciatic peripheral nerve block in rats. Methods Forty male Sprague–Dawley rats were randomly divided into 5 experimental groups: Group 1, sham; Group 2, perineural levobupivacaine (0.2 mL of a 0.5% solution) and subcutaneous saline; Group 3, perineural levobupivacaine (0.2 mL of a 0.5% solution) plus dexmedetomidine (20 µg/kg dexmedetomidine) and subcutaneous saline; Group 4, perineural saline and subcutaneous dexmedetomidine; and Group 5, perineural saline and subcutaneous saline. Pain reflexes in response to a thermal stimulus were measured at 0 and 240 minutes after drug administration by using a hot-plate and tail-flick tests. Neurobehavioral status, including sensory and motor functions, was assessed by an investigator who was blinded to the experimental groups every 30 minutes until normal functioning resumed. Results The sensory and motor blockades of the rats did not increase in the treatment with dexmedetomidine plus levobupivacaine when compared with the treatment with levobupivacaine alone at all the time points (P > 0.05). Compared with rats in Group 2, those in Group 3 showed significantly higher latency times at 30 and 60 minutes in the hot plate test (P < 0.01). At 30 and 60 minutes, the latency times of the rats in Group 3 were longer than those in Group 2 in the tail-flick test (P < 0.01). Furthermore, the durations of the complete sensory and motor blockade were similar when treatment with levobupivacaine plus dexmedetomidine was compared with treatment with levobupivacaine alone. Conclusions A 20µg/kg dose of dexmedetomidine added to levobupivacaine did not increase the duration of the sensory and motor blockades in rats. However, treatment with dexmedetomidine plus levobupivacaine increased the quality of analgesia in rats.

The effects of intracerebroventricular infusion of irisin on feeding behaviour in rats

Irisin, a novel exercise-induced myokine, has attracted attention with its effects on energy metabolism. This study was conducted to determine the possible effects of irisin on nutritional behaviour. In this study, 40 male Wistar Albino rats were separated into 4 groups (n=10 for each group). Osmotic mini-pumps were connected to metal cannulas implanted to lateral ventricle; and artificial cerebrospinal fluid (vehicle), and 10 and 100nM of irisin was infused for 7days. The daily food and water consumptions and body weights of rats were followed up. After the infusion, the animals were killed, and the hypothalamus and blood samples were collected. NPY, POMC, and UCP2 mRNA levels in the hypothalamus were examined by RT-PCR. In serum, leptin and ghrelin levels as well as the levels of metabolic parameters were measured by using ELISA. It was determined that irisin administration increased the daily food consumption (p<0.05), without causing significant changes in water consumption and body weight. Irisin also caused increases in ghrelin level in circulation and NPY and UCP2 mRNA levels in the hypothalamus, whereas it decreased the leptin level in circulation and POMC mRNA levels in the hypothalamus (p<0.05). Otherwise, irisin caused decrease in LDL, triglycerides and cholesterol levels, while increasing HDL and glucose levels (p<0.05). Results indicates that long-term irisin treatment increases food intake without increasing body weight associated with increased ghrelin, NPY and UCP2 mRNAs, and decreased leptin and POMC mRNA in the hypothalamus.

Effects of apelin on reproductive functions: relationship with feeding behavior and energy metabolism

Abstract Apelin is an adipose tissue derived peptidergic hormone. In this study, 40 male Sprague–Dawley rats were used (four groups; n = 10). Apelin-13 at three different dosages (1, 5 and 50 μg/kg) was given intraperitoneally while the control group received vehicle the same route for a period of 14 days. In results, apelin-13 caused significant decreases in serum testosterone, luteinizing hormone and follicle-stimulating hormone levels (p < 0.05). Administration of apelin-13 significantly increased body weights, food intake, serum low-density lipoprotein and total cholesterol levels (p < 0.05), but caused significant decreases in high-density lipoprotein levels (p < 0.05). Serum glucose and triglyceride levels were not significantly altered by apelin-13 administration. Significant decreases in both uncoupling protein (UCP)-1 levels in the white and brown adipose tissues and UCP-3 levels in the biceps muscle (p < 0.05) were noted. The findings of the study suggest that apelin-13 may not only lead to obesity by increasing body weight but also cause infertility by suppressing reproductive hormones.

Synthesis, Characterization, and Anticancer Activity of New Benzofuran Substituted Chalcones

Benzofuran derivatives are of great interest in medicinal chemistry and have drawn considerable attention due to their diverse pharmacological profiles including anticancer activity. Similarly, chalcones, which are common substructures of numerous natural products belonging to the flavonoid class, feature strong anticancer properties. A novel series of chalcones, 3-aryl-1-(5-bromo-1-benzofuran-2-yl)-2-propanones propenones (3a–f), were designed, synthesized, and characterized. In vitro antitumor activities of the newly synthesized (3a–f) and previously synthesized (3g–j) chalcone compounds were determined by using human breast (MCF-7) and prostate (PC-3) cancer cell lines. Antitumor properties of all compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell viability assay for the tested chalcone compounds was performed and the values of the compounds were calculated after 24-hour treatment. Our results indicate that the tested chalcone compounds show antitumor activity against MCF-7 and PC-3 cell lines ().

New platinum (II) and palladium (II) complexes of coumarin-thiazole Schiff base with a fluorescent chemosensor properties: Synthesis, spectroscopic characterization, X-ray structure determination, in vitro anticancer activity on various human carcinoma cell lines and computational studies

A new coumarin-thiazole based Schiff base (Ligand, L) and its Pd(II), Pt(II) complexes; ([Pd(L)2] and [Pt(L)2]), were synthesized and characterized using spectrophotometric techniques (NMR, IR, UV-vis, LC-MS), magnetic moment, and conductivity measurements. A single crystal X-ray analysis for only L was done. The crystals of L have monoclinic crystal system and P21/c space group. To gain insight into the structure of L and its complexes, we used density functional theory (DFT) method to optimize the molecules. The photophysical properties changes were observed after deprotonation of L with CN- via intermolecular charge transfer (ICT). Additionally, as the sensor is a colorimetric and fluorimetric cyanide probe containing active sites such as coumarin-thiazole and imine (CH=N), it showed fast color change from yellow to deep red in the visible region, and yellow fluorescence after CN- addition to the imine bond, in DMSO. The reaction mechanisms of L with CN-, F- and AcO- ions were evaluated using 1H NMR shifts. The results showed that, the reaction of L with CN- ion was due to the deprotonation and addition mechanisms at the same time. The anti-cancer activity of L and its Pd(II) and Pt(II) complexes were evaluated in vitro using MTT assay on the human cancer lines MCF-7 (human breast adenocarcinoma), LS174T (human colon carcinoma), and LNCAP (human prostate adenocarcinoma). The anti-cancer effects of L and its complexes, on human cells, were determined by comparing the half maximal inhibitory concentration (IC50) values. The activity results showed that, the Pd(II) complex of L has higher anti-tumor effect than L and its Pt(II) complex against the tested human breast adenocarcinoma (MCF-7), human prostate adenocarcinoma (LNCAP), and human colon carcinoma (LS174T) cell lines.

ACA, an inhibitor phospholipases A2 and transient receptor potential melastatin-2 channels, attenuates okadaic acid induced neurodegeneration in rats

Aim: In recent studies, it has been shown that the Transient Receptor Potential Melastatin‐2 Channels (TRPM2) and Phospholipases A2 (PLA2) inhibitors may have a protective effect on neurons. This study was aimed to investigate the protective effect of TRPM2 and PLA2 inhibitor N‐(p‐amylcinnamoyl) Anthranilic Acid (ACA) in a neurodegenerative model induced by Okadaic Acid (OKA). Main methods: OKA (200 ng/10 &mgr;l) was administered bilateral intracerebroventricularly as a single injection. Key findings: OKA‐treated rats showed significant impairments of spatial memory in Morris Water Maze Test. OKA‐induced memory‐impaired rats showed increased numbers of degenerated neurons and Caspase‐3, tau phosphorylated ser396, &bgr;‐amyloid positive cells in the hippocampus and cerebral cortex. Furthermore, OKA‐treated rats exhibited significantly increased MDA, TNF‐&agr; levels, and decreased SOD, GSH‐PX enzyme activates and GSH levels of the tissues. ACA administration ameliorated OKA‐induced memory impairment in rats. The ACA treatment also increased SOD and GSH‐PX enzyme activation and GSH levels, and conversely decreased the levels of MDA, TNF‐&agr;. It was found that the numbers of the degenerated neurons and Caspase‐3 positive cells of cortex and hippocampus regions were significantly reduced. Significance: ACA administration attenuates the oxidative stress and neuroinflammation of OKA‐induced neurodegeneration; and ameliorates the cognitive decline and neurodegeneration.

Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism.

Synthesis, structural and thermal characterizations and in vitro cytotoxic activities of new cyclotriphosphazene derivatives

GRAPHICAL ABSTRACT ABSTRACT We investigated the cytotoxic effects of the newly synthesized cyclotriphosphazene derivatives on A2780 (ovarian), PC-3 and LNCaP (prostate) cancer cell lines. 4′-hydroxy-substituted-chalcone compounds (2–8) were reacted with diphenyl-cyclotriphosphazene (DPP) in the presence of acetone/K2CO3 in order to obtain novel cyclotriphosphazene compounds (DPP 2–8). The structures of DPP 2–8 were characterized by MALDI-TOF mass spectrometry, FT-IR, elemental analysis, 1H, 13C-APT, and 31P NMR measurements. The thermal properties of all phosphazene compounds have been studied after synthesis and characterization procedure. The cytotoxic effects of DPP 2–8 were examined primarily by applying the MTT method based on the measurement of mitochondrial activity. In this regard, several phosphazene compounds have shown high chemotherapeutic effect at low dose (p < 0.05). When the cytotoxic effects of DPP 2–8 at doses of 1, 5, 25, 50 and 100 µM on A2780 cells were examined, it was observed that DPP-3, DPP-4, DPP-5 and DPP-7 were more effective than other derivatives suggested by their high Log IC50 values (p < 0.05). The compounds DPP 2–8 possess cytotoxic activity against PC-3 and LNCaP cells (especially compounds DPP-4 and DPP-5, p < 0.05).