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We previously reported that intracerebroventricularly (ICV) injected arachidonic acid (AA) could produce pressor and bradycardic responses on the cardiovascular system and hyperventilation effect on the respiratory system by activating cyclooxygenase (COX). We also demonstrated that centrally injected AA-induced cardiovascular and respiratory responses were mediated by COX-metabolites, such as thromboxane A2 (TXA2), prostaglandin (PG) D, PGE, and PGF2α. Brain tissue is also able to express the lipoxygenase (LOX) enzyme and LOX-induced AA-metabolites. The current study was designed to investigate the possible mediation of the central LOX pathway in AA-induced cardiorespiratory effects in anesthetized rats. Central pretreatment with different doses of a non-selective LOX inhibitor, nordihydroguaiaretic acid (NDGA) (500 and 1000 μg; ICV) partially blocked the AA (0.5 μmol; ICV)-evoked pressor and bradycardic cardiovascular responses in male anesthetized Sprague Dawley rats. Pretreatment with different doses of NDGA (500 and 1000 μg; ICV) also reduced AA-induced hyperventilation responses, with an increase in tidal volume, respiratory rate and minute ventilation, in the rats. Moreover, AA-induced increasing pO2 and decreasing pCO2 responses were diminished by central NDGA pretreatment. In summary, our findings show that the central LOX pathway might mediate, at least in part, centrally administered AA-evoked cardiorespiratory and blood gases responses.

Arachidonic acid (AA), which is released from synaptic membrane phospholipid by neuroreceptor-initiated activation of phospholipase A(2), is abundant in the brain and works as a neurotransmitter and/or neuromodulator in the central nervous system. Recently we reported that centrally injected AA generated pressor and hyperventilation effects by activating thromboxane A(2) (TXA(2)) signaling pathway. The present study was designed to investigate the mediation of other metabolites of AA such as prostaglandin (PG) D, PGE and PGF(2 alpha), alongside TXA(2) in the AA-evoked cardiorespiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA caused pressor, bradycardic and hyperventilation responses by increasing pO(2) and decreasing pCO(2) in adult male anaesthetized Sprague Dawley rats. Pretreatment (i.c.v) with different doses of DP/EP prostanoid receptor antagonist, AH6809 or FP prostanoid receptor antagonist, PGF(2 alpha), dimethylamine partially blocked the cardiorespiratory and blood gas changes induced by AA. In conclusion, these data plainly report that central PGD, PGE or PGF(2 alpha) might mediate, at least partly, centrally administered AA-evoked cardiorespiratory and blood gas responses.

Arachidonic acid (AA), which is released from synaptic membrane phospholipid by neuroreceptor-initiated activation of phospholipase A

Objective: In the present study, we aimed to screen the cytotoxic, antimicrobial, anti-angiogenic and anti-tumorogenic activities of Anatolian Vipera ammodytes (Nose-horned Viper) crude venom. Material and methods: The cytotoxicity was screened against PC3, HeLa, CaCo-2, U-87MG, MCF-7 and Vero cells by using MTT assay. The antimicrobial activity on Escherichia coli ATCC 25922, E. coli 0157: H7, Enterococcus faecalis 29212, Enterococcus faecium DSM 13590, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Salmonella typhimirium CCM 5445, Proteus vulgaris ATCC 6957, Bacillus cereus ATCC 7064 and Candida albicans ATCC 10239 was assayed by determining the minimum inhibitory concentration using the broth dilution method. Anti-angiogenic and anti-tumorogenic activity was assessed by using chick chorioallantoic membrane (CAM) assay. Results: The IC50 value of V. ammodytes venom on cultured cells varied from 1.8 to 7.0 mu g/mL after 48 h treatment. Venom showed antimicrobial activity on P. vulgaris, S. aureus, S. epidermidis, E. faecium and C. albicans (the highest activity). The venom exhibited dose-dependent anti-angiogenic activity on CAM model at 2 and 10 mu g/mL doses with scores of 1.1 and 2.0, respectively. Conclusion: The results of the present study contributed to the knowledge of the biological activities of Anatolian V. ammodytes venom and showed its potential for further bioactivity guided characterization studies. Amaç: Bu çalışmada, Vipera ammodytes (Burunlu Engerek) ham zehrinin sitotoksik, antimikrobiyal, anti-anjiyojenik ve anti-tümör aktivitelerinin taranmasını amaçlanmıştır. Metod: PC3, HeLa, CaCo-2, U-87MG ve MCF-7 kanser hücre hatları ve bir normal hücre hattı (Vero) kullanılarak MTT testi ile sitotoksite taraması yapılmıştır. Antimikrobiyal aktivite broth seyreltme metodu kullanılarak hesaplanan minimum inhibitör konsantrasyon ile değerlendirilmiştir. Escherichia coli ATCC 25922, E. coli 0157:H7, Enterococcus faecalis 29212, Enterococcus faecium DSM 13590, Staphy- lococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Salmonella typhimirium CCM 5445, Proteus vulgaris ATCC 6957, Bacillus cereus ATCC 7064 ve Candida albicans ATCC 10239 türleri kullanılmıştır. Anti-anjiyoge- nik anti-tümör aktivite civciv koryoallantoik membran (CAM) modeli ile değerlendirilmiştir. Bulgular: V. ammodytes zehrinin 48 saat sonunda hüc- reler üzerindeki IC 50 değeri, 1.8 ve 7.0 μg/mL arasında değişmiştir. Zehir P. vulgaris, S. aureus, S. epidermidis ve C. albicans (en yüksek etki) üzerinde antimikrobiyal etki göstermiştir. CAM deney modelinde 2 ve 10 μg/mL zehir dozlarında (sırasıyla 1.1 ve 2.0 skorları ile) anjiyogenezde doza bağlı baskılanma görülmüştür. Sonuç: Bu çalışmanın sonuçları Anadolu'da bulunan V. ammodytes zehrinin sahip olduğu biyolojik aktiviteleri ortaya koymuş ve ileride yapılacak biyoaktivite rehberli karakterizasyon çalışmaları için sahip olduğu potansiyeli göstermiştir.

The purpose of the current study is to investigate the functional connections between the central histaminergic and cholinergic systems at NTS level in hypotensive condition. Experiments were carried out in male Wistar Albino rats. The hypotension was achieved by withdrawing a total volume of 1.5 ml blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in NTS area to measure extracellular ACh and Ch levels. The hemorrhage produced a severe and long-lasting decrease in mean arterial blood pressure (MAP) and increase in extracellular ACh and Ch levels in NTS. Administration of histamine intracerebroventricularly (i.c.v.) or into the NTS reversed the hemorrhagic hypotension by increasing MAP and heart rate. I.c.v. injection of histamine also caused the additional increase in extracellular ACh and Ch levels. Moreover, central histamine injection augmented intracytoplasmic AChE immunoreactivity in NTS. These changes were completely blocked by histaminergic H1 receptor antagonist chlorpheniramine, but histaminergic H2 receptor blocker ranitidine and histaminergic H3/H4 receptor antagonist thioperamide failed to produce these effects. In conclusion, these findings are interpreted that brain histaminergic H1 receptor activation by central histamine injection may promote cholinergic stimulation in the NTS and subsequently reverses the hypotension.

Amaç: Bu çalışmada, Vipera ammodytes (Burunlu Engerek) ham zehrinin sitotoksik, antimikrobiyal, anti-anjiyojenik ve anti-tümör aktivitelerinin taranmasını amaçlanmıştır.Metod: PC3, HeLa, CaCo-2, U-87MG ve MCF-7 kanser hücre hatları ve bir normal hücre hattı (Vero) kullanılarak MTT testi ile sitotoksite taraması yapılmıştır. Antimikrobiyal aktivite broth seyreltme metodu kullanılarak hesaplanan minimum inhibitör konsantrasyon ile değerlendirilmiştir. Escherichia coli ATCC 25922, E. coli 0157:H7, Enterococcus faecalis 29212, Enterococcus faecium DSM 13590, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Salmonella typhimirium CCM 5445, Proteus vulgaris ATCC 6957, Bacillus cereus ATCC 7064 ve Candida albicans ATCC 10239 türleri kullanılmıştır. Anti-anjiyogenik anti-tümör aktivite civciv koryoallantoik membran (CAM) modeli ile değerlendirilmiştir.Bulgular: V. ammodytes zehrinin 48 saat sonunda hücreler üzerindeki IC50 değeri, 1.8 ve 7.0 ?g/mL arasında değişmiştir. Zehir P. vulgaris, S. aureus, S. epidermidis ve C. albicans (en yüksek etki) üzerinde antimikrobiyal etki göstermiştir. CAM deney modelinde 2 ve 10 ?g/mL zehir dozlarında (sırasıyla 1.1 ve 2.0 skorları ile) anjiyogenezde doza bağlı baskılanma görülmüştür.Sonuç: Bu çalışmanın sonuçları Anadolu'da bulunan V. ammodytes zehrinin sahip olduğu biyolojik aktiviteleri ortaya koymuş ve ileride yapılacak biyoaktivite rehberli karakterizasyon çalışmaları için sahip olduğu potansiyeli göstermiştir., Objective: In the present study, we aimed to screen the cytotoxic, antimicrobial, anti-angiogenic and anti-tumorogenic activities of Anatolian Vipera ammodytes (Nosehorned Viper) crude venom.Material and methods: The cytotoxicity was screened against PC3, HeLa, CaCo-2, U-87MG, MCF-7 and Vero cells by using MTT assay. The antimicrobial activity on Escherichia coli ATCC 25922, E. coli 0157:H7, Enterococcus faecalis 29212, Enterococcus faecium DSM 13590, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228, Salmonella typhimirium CCM 5445, Proteus vulgaris ATCC 6957, Bacillus cereus ATCC 7064 and Candida albicans ATCC 10239 was assayed by determining the minimum inhibitory concentration using the broth dilu-tion method. Anti-angiogenic and anti-tumorogenic activ-ity was assessed by using chick chorioallantoic membrane (CAM) assay.Results: The IC50 value of V. ammodytes venom on cul-tured cells varied from 1.8 to 7.0 ?g/mL after 48 h treat-ment. Venom showed antimicrobial activity on P. vulgaris, S. aureus, S. epidermidis, E. faecium and C. albicans (the highest activity). The venom exhibited dose-dependent anti-angiogenic activity on CAM model at 2 and 10 ?g/mL doses with scores of 1.1 and 2.0, respectively.Conclusion: The results of the present study contributed to the knowledge of the biological activities of Anatolian V. ammodytes venom and showed its potential for further bioactivity guided characterization studies.

Arachidonic acid (AA) is a polyunsaturated fatty acid that is present in the phospholipids of the cell membranes of the body and is abundant in the brain. Exogenously administered AA has been shown to affect brain metabolism and to exhibit cardiovascular and neuroendocrine actions. However, little is known regarding its respiratory actions and/or central mechanism of its respiratory effects. Therefore, the present study was designed to investigate the possible effects of centrally injected AA on respiratory system and the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway on AA-induced respiratory effects in anaesthetized rats. Intracerebroventricular (i.c.v.) administration of AA induced dose- and time-dependent increase in tidal volume, respiratory rates and respiratory minute ventilation and also caused an increase in partial oxygen pressure (pO2) and decrease in partial carbon dioxide pressure (pCO2) in male anaesthetized Sprague Dawley rats. I.c.v. pretreatment with ibuprofen, a non-selective COX inhibitor, completely blocked the hyperventilation and blood gases changes induced by AA. In addition, central pretreatment with different doses of furegrelate, a TXA2 synthesis inhibitor, also partially prevented AA-evoked hyperventilation and blood gases effects. These data explicitly show that centrally administered AA induces hyperventilation with increasing pO2 and decreasing pCO2 levels which are mediated by the activation of central COX to TXA(2) signaling pathway. (C) 2016 Elsevier B.V. All rights reserved.

This study investigated the cardiovascular effects of nesfatin-1 in normotensive rats and animals subjected to hypotensive hemorrhage. Hemorrhagic hypotension was induced by withdrawal 2 mL blood/100 g body weight over a period of 10 min. Acute hemorrhage led to a severe and long-lasting decrease in mean arterial pressure (MAP) and heart rate (HR). Intracerebroventricularly (i.c.v.) administered nesfatin-1 (100 pmol) increased MAP in both normotensive and hemorrhaged rats. Nesfatin-1 also caused bradycardia in normotensive and tachycardia in hemorrhaged rats. Centrally injected nesfatin-1 (100 pmol, i.c.v.) also increased plasma catecholamine, vasopressin and renin concentrations in control animals and potentiated the rise in all three cardiovascular mediators produced by hemorrhage. These findings indicate that centrally administered nesfatin-1 causes a pressor response in conscious normotensive and hemorrhaged rats and suggest that enhanced sympathetic activity and elevated vasopressin and renin concentrations mediate the cardiovascular effects of the peptide.

Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investi- gated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL-temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/ FITC and TUNEL assays, and the effect of FCL on inva- sion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progres- sion, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergisti- cally increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract.