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    Efficacy of Sunitinib, Sunitinib-Hesperetin, and Sunitinib-Doxycycline Combinations on Experimentally-Induced Corneal Neovascularization
    (Taylor & Francis Inc, 2019) Ekim, Yeliz; Kara, Selcuk; Gencer, Baran; Karaca, Turan
    Purpose: To investigate the preventive effects of topical sunitinib, sunitinib-hesperetin and sunitinib-doxycycline combinations on corneal neovascularization (CNV), apoptosis and fibrosis in a corneal alkali burn model.Materials and Methods: The corneas of 32 Wistar albino rats were cauterized with silver nitrate to induce CNV. Four groups were created receiving artificial tears (sham), sunitinib (0.5 mg/ml), sunitinib-hesperetin (0.5 mg/ml-0.2 mg/ml), and sunitinib-doxycycline (0.5 mg/ml-20 mg/ml) treatments. Corneal photographs were taken on days 0, 7 and 15. Photographs of the cornea were digitally analyzed to measure the size of the neovascularization area in comparison to the total corneal surface area. On the 15th day, the animals were euthanized, and the eyes were enucleated for immunohistochemical staining to investigate neovascularization, apoptosis, and fibrosis.Results: CNV areas on the 7th day in the sunitinib (4.8%0.07%) and sunitinib-hesperetin (1.1%+/- 0.03%) groups were smaller than those in the sham group (33.9%+/- 0.12%) (p=0.001 and, p <0.001 respectively). On the 15th day, the CNV area in the sunitinib-hesperetin (20.8%+/- 0.37%) group was significantly smaller than that of the sham group (74.6%+/- 0.32%) (p=0.039). The combination groups had lower levels of VEGF, TUNEL and -SMA positivity than the sunitinib monotherapy group. TUNEL positivity was lowest in the sunitinib-hesperetin and sunitinib-doxycycline groups, and -SMA positivity was lowest in the sunitinib-hesperetin group.Conclusion: Topical sunitinib-hesperetin was more effective than sunitinib alone and the sunitinib-doxycycline combination in the treatment of CNV. The combination of sunitinib and hesperetin seems to be a promising treatment for preventing corneal fibrosis and apoptosis.
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    Protective Effect of Hesperetin and Naringenin against Apoptosis in Ischemia/Reperfusion-Induced Retinal Injury in Rats
    (Hindawi Ltd, 2014) Kara, Selcuk; Gencer, Baran; Karaca, Turan; Tufan, Hasan Ali; Arikan, Sedat; Ersan, Ismail; Karaboga, Ihsan
    Purpose. Hesperetin and naringenin are naturally common flavonoids reported to have antioxidative effects. This study was performed to investigate whether either hesperetin or naringenin has a protective effect against apoptosis on retinal ischemia/reperfusion (I/R) injury. Methods. Retinal I/R was induced by increasing the intraocular pressure to 150 mm Hg for 60 minutes. Thirty-three male Wistar albino rats were randomised into 5 groups named control, I/R + sham, I/R + solvent (DMSO), I/R + hesperetin, and I/R + naringenin. Animals were given either hesperetin, naringenin, or the solvent intraperitoneally immediately following reperfusion. Thickness of retinal layers and retinal cell apoptosis were detected by histological analysis, tunel assay, and immunohistochemistry assay. Results. Hesperetin and naringenin attenuated the I/R-induced apoptosis of retinal cells in the inner and outer nuclear cells of the rat retina. Retinal layer thickness of the naringenin treatment group was significantly thicker than that of the hesperetin, sham, and solvent groups (P < 0.05). Conclusions. Hesperetin and naringenin can prevent harmful effects induced by I/R injury in the rat retina by inhibiting apoptosis of retinal cells, which suggests that those flavanones have a therapeutic potential for the protection of ocular ischemic diseases.
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    The protective effects of dexmedetomidine against apoptosis in retinal ischemia/reperfusion injury in rats
    (Taylor & Francis Ltd, 2014) Gencer, Baran; Karaca, Turan; Tufan, Hasan Ali; Kara, Selcuk; Arikan, Sedat; Toman, Huseyin; Karaboga, Ihsan
    Objective: Dexmedetomidine is an alpha 2 adrenoceptor agonist and can be used for postoperative sedation, analgesia and anesthesia-sparing properties. Furthermore, the neuroprotective effects against ischemia/reperfusion (I/R) injury in the central nervous system have been shown in experimental studies. This study aimed to investigate the protective effects of dexmedetomidine against apoptosis in retinal I/R injury in the rat. Materials and methods: Retinal I/R injury was induced by transient elevation of intraocular pressure. Eighteen animals were divided into three groups (n = 6): sham, I/R and treatment. The I/R injury and protective effects of the dexmedetomidine were evaluated by retinal thickness determined by histological sections, terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) and immunohistochemistry of caspases 3. Results: A decrease in the retinal thickness and an increase in the apoptotic cells were found to be statistically significant in I/R and treatment groups when compared with the control group. However, in comparison with the I/R group we realized that the administration of dexmedetomidine reduced the thinning of retinal thickness and also decreased the number of caspases 3 and TUNEL-positive cells. Conclusion: Dexmedetomidine is protective against apoptosis in retinal I/R injury in rats.
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    Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model
    (Consel Brasil Oftalmologia, 2015) Arikan, Sedat; Ersan, Ismail; Karaca, Turan; Kara, Selcuk; Gencer, Baran; Karaboga, Ihsan; Tufan, Hasan Ali
    Purpose: This study aimed to investigate the effect of quercetin on apoptotic cell death induced by ischemia-reperfusion (I/R) injury in the rat retina. Methods: Twenty-four rats were divided into four equal groups: control, ischemic, solvent, and quercetin. I/R injury was achieved by elevating the intraocular pressure above the perfusion pressure. Intraperitoneal injections of 20 mg/kg of quercetin and dimethyl sulfoxide (DMSO) were performed in the quercetin and solvent groups, respectively, immediately prior to I/R injury, and the researchers allowed for the retinas to be reperfused. Forty-eight hours after injury, the thicknesses of the retinal ganglion cell layer (RGCL), inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL), and outer nuclear layer (ONL) were measured in all groups. Moreover, the numbers of terminal deoxynucleotidyl transferase dUTP nick-end-labeled [TUNEL (+)] cells and caspase-3 (+) cells in both INL and ONL were evaluated in all groups. Results: The administration of quercetin was found to reduce the thinning of all retinal layers. The mean thickness of INL in the quercetin and ischemic groups was 21 +/- 5.6 mu m and 16 +/- 6.4 mu m, respectively (P<0.05). Similarly, the mean thickness of ONL in the quercetin and ischemic groups was 50 +/- 12.8 mu m and 40 +/- 8.7 mu m, respectively (P<0.05). The antiapoptotic effect of quercetin in terms of reducing the numbers of both TUNEL (+) cells and caspase-3 (+) cells was significant in INL. The mean number of TUNEL (+) cells in INL in the ischemic and quercetin groups was 476.8 +/- 45.6/mm(2) and 238.72 +/- 251/mm(2), respectively (P<0.005). The mean number of caspase-3 (+) cells in INL of ischemic and quercetin groups was 633.6 +/- 38.7/mm(2) and 342.4 +/- 36.1/mm(2), respectively (P<0.001). Conclusion: The use of quercetin may be beneficial in the treatment of retinal I/R injury because of its antiapoptotic effect on the retinal layers, particularly in INL.