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Öğe Effect of Topically Applied Azithromycin on Corneal Epithelial and Endothelial Apoptosis in a Rat Model of Corneal Alkali Burn(Lippincott Williams & Wilkins, 2016) Arikan, Sedat; Karaca, Turan; Ertekin, Yusuf Haydar; Comez, Arzu Taskiran; Ersan, Ismail; Demirtas, Selim; Elmas, SaitPurpose: To investigate the antiapoptotic effect of topically administered azithromycin (AZM) on corneal epithelial and endothelial cells in a rat model of corneal alkali burn. Methods: Twenty-four Wistar albino rats were divided into 4 equal groups as pseudovehicle (group 1), control (group 2), alkali burned (group 3), and treatment (group 4) groups. Alkali injury was induced only in the right corneas of rats belonging to groups 3 and 4 using 1N NaOH. The rats in group 3 and the rats in group 4 were respectively treated either with an artificial tear gel or with 1.5% AZM eye drops for 5 days. At the fifth day of the experiment, the apoptosis in the corneal epithelium and endothelium of all rats was assessed using a terminal dUTP nick-end labeling (TUNEL) assay. In addition, tumor necrosis factor-alpha (TNF-alpha) density in the corneal epithelium was measured in all rats. Results: The mean numbers of TUNEL+ cells in the corneal epithelium and endothelium of rats in group 3 were 117.1 +/- 23.8 and 34.6.+/- 11.3, respectively, whereas in group 4, they were 75.8 +/- 15.7 and 14.7 +/- 3.5, respectively. Also the mean TNF-alpha densities in the corneal epithelium in group 3 and group 4 were 2.65 +/- 1.3 and 1.65 +/- 1.1, respectively. There was a significant decrease in the mean number of TUNEL+ cells in the corneal epithelium and endothelium and in the mean TNF-alpha density in the corneal epithelium of rats in group 4, when compared with group 3. Conclusions: Topically applied AZM can decrease TNF-alpha-induced apoptosis in corneal alkali burn.Öğe Evaluation of the protective effects of hesperetin against cisplatin-induced ototoxicity in a rat animal model(Elsevier Ireland Ltd, 2016) Kara, Medine; Turkon, Hakan; Karaca, Turan; Guclu, Oguz; Uysal, Sema; Turkyilmaz, Mehmet; Demirtas, SelimObjectives: We aimed to investigate the effects of hesperetin as a flavanon both histopathologically and immunohistochemically on cochlear apoptosis in a rat model of cisplatin-induced ototoxicity (CIO). The evaluation of the effects of hesperetin on cisplatin-induced hearing loss was performed using distortion product otoacoustic emission (DPOAE). Methods: Twenty-eight wistar albino rats were used in the current study. The rats were randomly divided into four groups with seven rats in each group. Group C was exposed to a single dose of cisplatin (12 mg/kg) by intraperitoneal injection. Group CH received intraperitoneally cisplatin (12 mg/kg) and hesperetin (20 mg/kg). Group H was exposed to hesperetin (20 mg/kg) intraperitoneally. The sham group (group S) received normal saline (6 cc) intraperitoneally. The measurements of DPOAE and signal-noise ratios (SNR) were performed before the treatment and again on the first and 6 days after administration of the drugs. Rats were sacrificed and cochleae were dissected 10 days after drug administration. The cochlear tissue was assessed in all groups by histopathologic, immunohistochemical and TUNEL assay. In addition, serum oxidative stress markers and antioxidant parameters were analyzed. Results: There was a significant difference between the basal value and the sixth day at frequencies 8.4, 9.6 and 9.96 for group C. We also found a significant difference between the first and sixth day at frequencies 7.2, 8.4, 9.6 and 9.96. On the 6th day, there were significant differences between C and S groups at all frequencies except 2.4. We showed a significant difference between C and H groups at frequencies 4.8, 6.0, 8.4, 9.6 and 9.96. There was also a significant difference between C and CH groups at frequencies 2.4, and 3.6. We found lower levels of oxidants and higher levels of antioxidants in CH group as compared to C group. C group had a significantly greater number of TUNEL-positive cells than did S, H and CH groups. The number of TUNEL-positive cells in CH group was higher than in S and H groups. There was a significant difference between the positive PCNA cells of CH group compared to S and H groups in spiral ganglion and stria vascularis. In addition, there were no positive PCNA cells in C group. Conclusions: Hesperetin may prevent ototoxicity by increased antioxidant enzymes and reduced oxidant parameters and protected against apoptosis resulting from a proliferation of cochlear cells in CIO. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Öğe 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, IhsanPurpose. 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.Öğe 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 AliPurpose: 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.Öğe The effect of hesperetin on ischemia-reperfusion injury in rat ovary(Springer Heidelberg, 2014) Gungor, Ayse Nur Cakir; Gencer, Meryem; Karaca, Turan; Hacivelioglu, Servet; Uysal, Ahmet; Korkmaz, Fatma; Demirtas, SelimHesperidin (HES), a citrus fruit extract, has beneficial effects on various ischemia/reperfusion (I/R) models. We aimed to evaluate the possible positive effects of hesperetin (HPT), an active metabolite of HES, on a rat ovarian I/R model. We divided 24 Wistar Albino rats into four groups. Group I (n = 6) was sham operated, Group II (n = 6) was the I/R group, Group III (n = 6) was the I/R + solvent group and Group IV (n = 6) was the I/R + HPT group. Three hours of ischemia and 3 h of reperfusion were performed on each rat in Groups II, III, and IV. Dimethyl sulfoxide (DMSO) was given intraperitoneally to the rats in the III. Group, and 50 mg/kg of HPT dissolved in DMSO was given intraperitoneally to the rats in the IV. Group 30 min before reperfusion. After 3 h of reperfusion, the ipsilateral ovaries of the rats were examined immunohistochemically to detect apoptosis. Hematoxylin and eosin (H and E) staining demonstrated less edema and hemorrhage in the group where HPT was applied. Caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining showed significantly lower apoptosis in the group where HPT was used when compared to either the I/R or solvent group. To the best of our knowledge, this is the first study that shows the beneficial effects of HPT in an ovarian I/R injury. HPT improved tissue damage and apoptosis caused by I/R injury. To identify the possible positive effects of HPT in ovarian torsion of humans and use in clinical practice, more studies must be performed.Öğe The effects of apomorphine on paracetamol-induced hepatotoxicity in rats(C M B Assoc, 2017) Sehitoglu, Muserref Hilal; Yayla, Muhammet; Kiraz, Asli; Oztopuz, Rahime Ozlem; Bayir, Yasin; Karaca, Turan; Khalid, SumbulIt is becoming progressively more understandable that overdose of paracetamol in both humans and animals causes severe hepatotoxicity. Apomorphine is known as a neuroprotective agent. Due to the protective effect, apomorphine had been tested in experimental studies on different models. Findings obtained through series of expriments suggested that apomorphine may also be useful in liver toxicity. The aim of this study is to investigate the relationship among the hepatoprotective mechanism of apomorphine and to determine the possible role of apomorphine on paracetamol-induced hepatotoxicity in rats. 30 Sprague Dawley rats (adult male) were distributed into 5 groups. Group 1 was the control group and did not receive any medication. Group 2 received only paracetamol 2 g/kg by intragastric gavage to induce hepatotoxicity. Groups 3 and 4 were given apomorphine 1 mg/kg and 2 mg/kg by intraperitoneal injection, respectively. Groups 3 and 4 were given 2g/kg of Paracetamol. In Group 5, rats were treated with 2 mg/kg of apomorphine. Drug-treated rats were given food for the next 24 h until they were sacrified. Moreover, we also performed AST, ALT measurements in serum, MDA and SOD levels in liver tissues and histopathological analysis of the liver in all groups. Apomorphine had positive effects on both liver enzymes, oxidative stress markers and histopathological results in paracetamol-induced hepatotoxicity. Additionally, apomorphine at 2 mg/kg dose was significantly more protective as compared to 1 mg/kg as evidenced by the histopathological examination results. It was thought that apomorphine was found hepatoprotective on paracetamol-induced hepatotoxicity, especially at higher doses such as 2 mg/kg.Öğe The protective effect of quercetin on IMA levels and apoptosis in experimental ovarian ischemia-reperfusion injury(Elsevier Science Bv, 2014) Gencer, Meryem; Karaca, Turan; Gungor, Ayse N. C.; Hacivehoglu, Servet O.; Demirtas, Selim; Turkon, Hakan; Uysal, AhmetObjective: To investigate the protective effect of quercetin (QE), an anti-inflammatory and anti-oxidant agent, on torsion-detorsion induced histopathological changes and blood IMA levels in experimental ovarian ischemia-reperfusion (IR) injury. Study design: Twenty-four female Wistar rats were randomly divided into four groups in this study (n = 6). Group I, (sham operation); Group II, torsion-detorsion plus saline (IR); Group III, torsiondetorsion plus solvent (dimethylsulfoxide: DMSO, IR + DMSO); Group IV, torsion-detorsion plus 15 mg/kg/bw quercetin (IR + QE) injected intraperitoneally 30 min prior to detorsion. After 3 h of reperfusion, the right ovaries were removed surgically. The ovary tissue samples were fixed in 10% formalin solution for histopathological and immunohistochemical examination. Blood samples were obtained at the end of the procedures for each group of animals. Results: Ovarian sections in Groups II and III showed higher follicular cell degeneration, hemorrhage, vascular congestion and edema when compared with Group I. Administration of quercetin in rats significantly prevented degenerative changes in the ovary. Significantly less histopathological changes were found in Group IV compared with Groups II and III. Caspase-3 and TUNEL positive cells were detected in the ovarian surface, follicle epithelium, and stromal cells in all experimental groups, and there was a significant increase in Groups II and III compared with Group I (P < 0.05). Treatment with quercetin decreased the number of caspase-3 and TUNEL positive cells. IR increased the ischemia modified albumin (IMA) levels in comparison to the sham group (1.06 +/- 0.10 ABSU and 0.92 +/- 0.08 ABSU, P < 0.05). Quercetin administration before IR reduced the levels of IMA (0.93 + 0.08 ABSU, P < 0.05). Conclusion: Administration of quercetin is effective in preventing tissue damage induced by IR injury in ovaries. (C) 2014 Elsevier Ireland Ltd. All rights reserved.Öğe 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, IhsanObjective: 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.
