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    Low level laser application reduces the effect of 5 fluorouracil/leucovorin combination on human breast cancer cells
    (2020) Güler, Yılmaz; Övey, İshak Suat; Samur, Dilara Nemutlu; Karabulut, Bayhan
    Aim : 5-fluorouracil has been widely used in breast cancer treatment. Low level laser therapy (LLLT) has been shown to modulate biological processes and used in cancer treatment. It has been reported that apoptosis is induced by stimulation of transient receptor potential protein channels in numerous cancer cells, including breast cancer. We aimed to reveal the effects of 5-fluorouracil / Leucovorin (5-FU/LV) and . low level laser on apoptosis via transient receptor protein ancyrin 1 (TRPA1) channels. Material and Methods: Breast cancer cells (MCF-7) were cultured and cells were divided into seven main groups. Cells were incubated with 5-FU/LV and LLLT exposure separately and together performed on MCF-7 cell cultures. Cell cultures incubated with TRPV1 channel antagonist capsazepin and stimulator capsaicin. The effects of 5-FU and LLLT were investigated on all molecular pathways of apoptosis. Results: It was found that the levels of apoptosis in 5-FU/LV group were significantly increased in cancer cells compared to control group .TRPA1 channel stimulator administration resulted in significantly increased apoptosis levels compared to the control group, in 5-FU/LV + low level laser group the apoptosis level significantly reduced compared to 5-FU/LV-only group. (p<0.001) Conclusion: It has been shown that 5-FU/LV significantly increases apoptosis in breast cancer cells, however low level laser administration decreases apoptosis and suppressed apopitotic effect of 5-FU/LV significantly on breast cancer cells.
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    The effects of metamizole on hematopoietic progenitor cells: Suppression of hematopoiesis stimulation in vitro
    (2023) Maytalman, Erkan; Samur, Dilara Nemutlu; Günizi, Özlem Ceren; Kozanoğlu, lknur
    BACKGRAUND: There is evidence that the adverse effects of metamizole occur due to the effect of the drug on the hematopoietic stem/progenitor cells, and therefore, the disruption of hematopoiesis. Therefore, our study aimed to evaluate the effects of metamizole on hematopoietic stem/progenitor cells using cell culture techniques. MATERIAL AND METHODS: In our study, samples were taken from stem cell products of healthy allogeneic stem cell transplant donors. The colony-forming unit (CFU) assay was used for the cells obtained from these samples. In addition, the drug effects on cell proliferation were evaluated with the MTT. Furthermore, the cell colonies were labelled with immunofl uorescent antibodies and the effects of metamizole on cell types formed in culture were evaluated. RESULTS: We determined that metamizole negatively affects the proliferation of cells, especially starting from 10 ?M. As a result of the evaluation of colonization, we saw that the number of colonies decreased with increasing concentrations. Granulocyte-macrophage colonies were more affected at increasing concentrations than other colonies. As a result of the evaluations of our in vitro study, it was also shown as an important fi nding that the individual effects of the drug were highly variable. CONCLUSION: CFU method can be used as a suitable method to investigate the effects of drugs and toxic substances on hematopoiesis. We also think it may be suitable for pre-analysing hematopoietic side effects in new drug research. In addition, using stem cell samples in studies may contribute more easily to the in vitro simulation of hematopoietic differentiations (Fig. 7, Ref. 29)
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    The possible mechanisms of protocatechuic acid-induced central analgesia
    (Elsevier Science Bv, 2018) Arslan, Rana; Aydın, Şule; Samur, Dilara Nemutlu; Bektaş, Nurcan
    It is aimed to investigate the central antinociceptive effect of protocatechuic acid and the involvement of stimulation of opioidergic, serotonin 5-HT2A/2C. alpha 2-adrenergic and muscarinic receptors in protocatechuic acid-induced central analgesia in mice. Time-dependent antinociceptive effects of protocatechuic acid at the oral doses of 75,150 and 300 mg/kg were tested in hot-plate (integrated supraspinal response) and tail-immersion (spinal reflex) tests in mice. To investigate the mechanisms of action; the mice administered 300 mg/kg protocatechuic acid (p.o.) were pre-treated with non-specific opioid antagonist naloxone (5 mg/kg, i.p.), serotonin 5-HT2A/(2c) receptor antagonist ketanserin (1 mg/kg, i.p.), alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, l.p.) and non-specific muscarinic antagonist atropine (5 mg/kg, l.p.), respectively. The antinociceptive effect of protocatechuic acid was observed at the doses of 75, 150 and 300 mg/kg in tail-immersion test, at the doses of 150 and 300 mg/kg in hot-plate test at different time interval. The enhancement in the latency of protocatechuic acid-induced response to thermal stimuli was antagonized by yohimbine, naloxone and atropine in tail-immersion test, while it was antagonized only by yohimbine and naloxone pretreatments in hot-plate test. These results indicated that protocatechuic acid has the central antinociceptive action that is probably organized by spinal mediated cholinergic and opiodiergic, also spinal and supraspinal mediated noradrenergic modulation. However, further studies are required to understand how protocatechuic acid organizes the interactions of these modulatory systems. As a whole, these findings reinforce that protocatechuic acid is a potential agent that might be used for pain relief. Additionally, the clarification of the effect and mechanisms of action of protocatechuic acid will contribute to new therapeutic approaches and provide guidance for new drug development studies. (C) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.
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    Valnoctamide: The effect on relieving of neuropathic pain and possible mechanisms
    (Elsevier Science Bv, 2018) Samur, Dilara Nemutlu; Arslan, Rana; Aydın, Şule; Bektaş, Nurcan
    The purpose of this study is to assess the possible anti-allodynic and antihyperalgesic effect of valnoctamide, an amide derivative of valproic acid, at the doses of 40, 70 and 100 mg/kg (i.p.) in neuropathic pain model induced by chronic constriction injury in rats, by using dynamic plantar test and plantar test (Hargreaves method), and to evaluate that the possible role of certain serotonin, noradrenergic, opioid and GABAergic receptors by pretreatment with 1 mg/kg (i.p.) ketanserin, yohimbine, naloxone and 0.5 mg/kg (i.p.) bicuculline, respectively. 70 and 100 mg/kg valnoctamide significantly increased the mechanical and thermal thresholds decreasing with the development of neuropathy and demonstrated anti-allodynic and antihyperalgesic activity. Limited contribution of serotonin 5-HT2A/2C receptors and alpha 2-adrenoceptors, and significant contribution of GABA(A) and opioid receptors to the anti-allodynic activity have been identified whereas remarkable contribution of opioid receptors and significant contribution of serotonin 5-HT2A/2C receptors, alpha 2-adrenoceptors, GABA(A) receptors to the antihyperalgesic activity have been identified. Based upon these findings and considering that valnoctamide has safer side-effect profile, it is possible to say that valnoctamide is a potential agent that might be used alone or in combination with the other effective therapies in the alleviating of neuropathic pain.