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    Effects of intrathecai verapamil on cerebral vasospasm in experimental rat study
    (Elsevier Science Inc, 2019) Akkaya, Enes; Evran, Sevket; Calis, Fatih; Çevik, Serdar; Hanimoglu, Hakan; Seyithanoglu, Mehmet Hakan; Katar, Salim; Karatas, Ersin; Kocyigit, Abdurrahim; Saglam, Mustafa Yasin; Hatiboglu, Mustafa Aziz; Kaynar, Mehmet Yasar
    BACKGROUND: Verapamil a calcinarn channel blacker, has shown promising results on cerebral vasospasm. However, it has not yet been accepted for treatment or prevention purposes because of the associated side effects, Although the effective results of nimodipine and nicardipine's intrathecal administration are well known, intrathecal verapamil has not been considered earlier. We used an experimental subarachnoid hemorrhage induced vasospasm model for the evaluation of vasodilator and neuroprotective effects of intrathecal verapamil, METHODS: A total of 24 Sprague-Davvley rats were randomly divided into the following 3 groups: group 1 (sham), group 2 (subarachnoid hemorrhage), and group 3 {verapamil). A double hemorrhage method was used. Group 2 did not receive any treatment. Verapamil (Eporon, Hem Ilac, Turkey) at a dose of 1000 mu g/kg was given intrathecally to group 3 rats. The animals were euthanized on day 7 of the procedure. Arterial wall thickness and lumen diameter in the basilar arterial cross-sectional areas, endothelin-1 serum level, oxidative stress index, and apoptosis were measured in all groups. RESULTS: In the verapamil group, wall thickness, endothelin-1 level, oxidative stress index, and apoptosis were found to be significantly lower than the subarachnoid hemorrhage group, but the lumen diameter was found to be greater, Intrathecal verapamil was found to decrease vasospasm parameters and apoptosis and increase the antioxidant and antiapoptotic pathways. CONCLUSIONS: Our findings suggest that intrathecal verapamil can prevent vasospasnt oxidative stress, and apoptosis after experimental subarachnoid hemorrhage.
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    Induction of Apoptosis through Oxidative Stress Caused by Rubus tereticaulis Leaves Extracts in A549 Cells
    (İstanbul Üniversitesi Yayınevi, 01.11.2024) Nur, Öter Gamze; Durmus, Ezgi; Sen, Ali; Kocyigit, Abdurrahim
    Objective:Plants have been used for medicinal purposes since the beginning of human history and form the basis of modern medicine, and they are also the source of most chemotherapeutic drugs for cancer treatment. This study aims to investigate for the first time the cytotoxic and apoptotic effects of the active ethanol (RTE) and chloroform (RTC) extracts of Rubus tereticaulis leaves in the A549 non-small-cell lung cancer cell line. Materials and Methods:A549 cells were treated with RTE and RTC individually. The MTT assay was used to quantitatively detect RTE and RTC’s cytotoxic effects. The fluorescent signal indicator H2DCF-DA was used to detect cellular reactive oxygen species (ROS) production. Apoptosis was evaluated by fluorescence microscope after acridine orange/ethidium bromide fluorescent staining, annexin V-FITC and immunoblotting analyses, immunofluorescence, and imaging. Results:Both RTE and RTC induced cytotoxicity in A549 cells in a dose-dependently, which was accompanied with induced ROS accumulation. Both early and late apoptotic cells detected by flow cytometry were increased in the RTE- and RTC-treated cells. In addition, the results show RTC to have higher cytotoxic and apoptotic effects and increased ROS-generation capacity than RTE. Therefore, the polarity of the solvent used to exert the anticancer effect of R. tereticaulis leaves is crucial. Conclusion:This is the first anti-cancer activity study on R. tereticaulis. The results suggest R. tereticaulis leaves to have an anti-cancer effect on lung cancer cells through ROS-mediated apoptosis and RTC to be an effective therapeutic/adjuvant strategy in cancer treatment.
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    Investigation of irisin?s role in pubertal onset physiology in female rats
    (Elsevier Science Inc, 2023) Kutlu, Esra; Ozgen, Lker Tolga; Bulut, Huri; Kocyigit, Abdurrahim; Ustunova, Savas; Huseyinbas, Onder; Torun, Emel
    Objective: The timing of pubertal development is closely related to metabolic status and energy reserves. It is thought that irisin, which is involved in the regulation of energy metabolism and is shown to be present in the hypothalamo-pituitary-gonadal (HPG) axis, may play a role in this process. In our study, we aimed to investigate the effect of irisin administration on pubertal development and HPG axis in rats. Design-methods: 36 female rats were included in the study were divided into 3 groups: 100 ng/kg/day irisin treatment group (irisin-100), 50 ng/kg/day irisin treatment group (irisin-50), and control group. On the 38th day, serum samples were taken to determine levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol and irisin. Brain hypothalamus samples were taken to determine levels of pulsatile gonadotropin-releasing hormone (GnRH), kisspeptin, neurokinin-B, dynorphin (Dyn), and makorin ring finger protein-3 (MKRN3).Results: Vaginal opening and estrus were seen firstly in the irisin-100 group. At the end of the study, the highest rate of vaginal patency was found in the irisin-100 group. Hypothalamic protein expression levels of GnRH, NKB and Kiss1 in homogenates; serum FSH, LH, and estradiol levels were the highest in the irisin-100 group, followed by the irisin-50 and control groups, respectively. Ovarian sizes were significantly greater in the irisin-100 group compared to the other groups. The hypothalamic protein expression levels of MKRN3 and Dyn were the lowest in the irisin-100 group.Conclusions: In this experimental study, irisin triggered the onset of puberty in a dose-dependent manner. Irisin administration caused the excitatory system to dominate in the hypothalamic GnRH pulse generator.