Person: KABASAKAL, LEVENT
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KABASAKAL
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LEVENT
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Publication Open Access Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats(BIOSCIENTIFICA LTD, 2006-05) VELİOĞLU ÖĞÜNÇ, AYLİZ; Sener, G.; Kabasakal, L.; Atasoy, B. M.; Erzik, C.; Velioglu-Ogunc, A.; Cetinel, S.; Contuk, G.; Gedik, N.; Yegen, B. C.The objective of this study was to examine the potential radioprotective properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative organ damage induced by irradiation. Sprague-Dawley rats were pre-treated with saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body irradiation (800 cGy). A group of rats were decapitated at 6 h after exposure to irradiation, while another group was followed for 72 h after irradiation, during which saline or PTU injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde (MDA; an index of lipid peroxidation) and glutathione (GSH, an antioxidant) levels, myeloperoxidase activity (MPO; an index of tissue neutrophil accumulation) and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH), an indicator of tissue damage, and turnout necrosis factor-alpha (TNF alpha) were assayed in serum samples. Irradiation caused a significant decrease in GSH level, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the tissues studied (P < 0.05-0.001). Similarly, serum TNFa and LDH were elevated in the irradiated rats as compared with the control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Our results suggested that PTU-induced hypothyroidism reduces oxidative damage in the lung, hepatic, renal and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.Publication Metadata only Mesna (2-mercaptoethane sulfonate) prevents ischemia/reperfusion induced renal oxidative damage in rats(PERGAMON-ELSEVIER SCIENCE LTD, 2004) ŞENER, GÖKSEL; Kabasakal, L; Sehirli, AO; Cetinel, S; Cikler, E; Gedik, N; Sener, GReoxygenation of the ischemic tissue promotes the generation of various reactive oxygen metabolites (ROM) which are known to have deleterious effects on various cellular functions. This study was designed to determine the possible protective effect of mesna (2-Mercaptoethane Sulfonate) on renal ischemia/reperfusion (I/R) injury. Wistar albino rats were unilaterally nephrectomized, and 15 days later they were subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Mesna (MESNA, 150 mg/kg, i.p.; an effective dose against I/R injury) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. Kidney samples were taken for histological examination or determination of the free radicals, renal malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Renal tissue collagen content, as a fibrosis marker was also determined. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. The results demonstrated that renal I/R caused nephrotoxicity, as evidenced by increases in blood urea and creatinine levels, which was reversed by MESNA treatment. Increased free radical levels, as assessed by nitroblue-tetrazolium test were reduced with MESNA. Moreover, the decrease in GSH and increases in MDA levels, and MPO activity induced by I/R indicated that renal injury involves free radical formation. Treatment of rats with MESNA restored the reduced GSH levels while it decreased MDA levels as well as MPO activity. Increased collagen contents of the kidney tissues by I/R were reversed back to the control levels by MESNA treatment. Since MESNA administration reversed these oxidant responses, improved renal function and microscopic damage, it seems likely that MESNA protects kidney tissue against I/R induced oxidative damage. (C) 2004 Elsevier Inc. All rights reserved.Publication Metadata only Chitosan/Short Hairpin RNA Complexes for Vascular Endothelial Growth Factor Suppression Invasive Breast Carcinoma(MARY ANN LIEBERT, INC, 2010) EREN, FATİH; Salva, Emine; Kabasakal, Levent; Eren, Fatih; Cakalagaoglu, Fulya; Ozkan, Naziye; Akburga, JuelideVascular endothelial growth factor (VEGF) plays a critical role in angiogenesis. The aim of this study was to use chitosan/short hairpin VEGF (shVEGF) [short hairpin RNA (shRNA)-expressing pDNA targeting VEGF-A] complexes in the treatment of rat breast cancer model. Therefore, chitosan/shVEGF complexes were prepared in (2/1) ratio and injected to the breast-tumor bearing Sprague-Dawley rats. Intratumoral and intraperitoneal injections were applied and compared. Tumor volumes were measured during the 36 days. To investigate the effect of complexes on the VEGF expression, VEGF were analyzed by immunohistochemistry and western blotting. The mRNA levels of VEGF were determined by real-time polymerase chain reaction. Tumor volume decreased at the end of experiments after shRNA treatment. The highest suppression in the tumor volume was observed after intratumoral complex injection to rats (96%). Compared with intratumoral and intraperitoneal injection, higher tumor inhibition was obtained with intratumoral injection. Free shRNA injection indicated lower tumor suppression. The immunohistochemistry and western blotting results correlated with the real-time polymerase chain reaction and tumor volume measurements. The data suggest that chitosan/shVEGF complexes can be used to inhibit tumor growth in breast carcinoma model of rats.Publication Metadata only Dapagliflozin attenuates depressive-like behavior of male rats in the forced swim(ELSEVIER, 2019) YAVUZ, AYŞE NUR; Cam, M. E.; Hazar-Yavuz, A. N.; Yildiz, S.; Keles, R.; Ertas, B.; Kabasakal, L.Publication Open Access A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches(ELSEVIER, 2020-10) YAVUZ, AYŞE NUR; Cam, Muhammet Emin; Hazar-Yavuz, Ayse Nur; Cesur, Sumeyye; Ozkan, Ozan; Alenezi, Hussain; Sasmazel, Hilal Turkoglu; Eroglu, Mehmet Sayip; Brako, Francis; Ahmed, Jubair; Kabasakal, Levent; Ren, Guogang; Gunduz, Oguzhan; Edirisinghe, MohanProgesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for infra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth.Publication Metadata only Local Delivery of Chitosan/VEGF siRNA Nanoplexes Reduces Angiogenesis and Growth of Breast Cancer In Vivo(MARY ANN LIEBERT, INC, 2012) EREN, FATİH; Salva, Emine; Kabasakal, Levent; Eren, Fatih; Ozkan, Naziye; Cakalagaoglu, Fulya; Akbuga, JulideVascular endothelial growth factor (VEGF) is the important angiogenic factor associated with tumor growth and metastasis in a wide variety of solid tumors. The aim of this study is to investigate the tumor suppressive effect of chitosan/small interfering RNA (siRNA)-VEGF nanoplexes in the rat breast cancer model. Chitosan/siRNA nanoplexes (siVEGF-A, siVEGFR-1, siVEGFR-2) and NRP-1 were prepared in a 15 to1 ratio and injected (intratumorally) into the breast-tumor-bearing Sprague-Dawley rats. Tumor volumes were measured during 21 days. To investigate the effect of chitosan/siRNA nanoplexes on VEGF expression in tumors, VEGF was analyzed with immunohistochemistry and western blotting. The mRNA levels of VEGF in tumor samples were determined with real-time PCR (RT-PCR). After siRNA treatment, a marked reduction in tumor volumes was measured in complex-injected rats (97%). Free siRNA injection showed lower tumor inhibition. Reduction of VEGF protein was also shown with western blotting and immunohistochemistry. Similar results were obtained with RT-PCR also. These results indicate that the chitosan/siRNA targeting to VEGF nanoplexes have a remarkably suppressive effect on VEGF expression and tumor volume in breast cancer model of rats.Publication Metadata only 2-mercaptoethane sulfonate (MESNA) protects against biliary obstruction-induced oxidative damage in rats(ELSEVIER IRELAND LTD, 2006) ERCAN, FERİHA; Sener, G; Kabasakal, L; Sehirli, O; Ercan, F; Gedik, NThe aim of this study was to assess the antioxidant and antifibrotic effects of chronic administration of 2-mercaptoethane sulfonate (MESNA) on oxidative liver damage and fibrosis induced by biliary obstruction in rats. Liver fibrosis was induced in male Wistar albino rats by bile duct ligation and scission (BDL). MESNA (150 mg/kg, i.p.) or saline was administered for 28 days. At the end of the experiment, rats were killed by decapitation. Serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were determined to assess liver function. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehidrogenase (LDH) were also assayed in serum samples. Liver tissues were taken for determination of the free radicals, hepatic malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Hepatic collagen content, as a fibrosis marker was also determined. Serum AST, ALT, LDH and TNF-alpha levels were elevated in the BDL group as compared to control group, while this increase was significantly decreased by MESNA treatment. BDL caused a significant (p < 0.05-0.001) decrease in GSH levels while MDA levels and MPO activity were increased in the liver tissue. These changes were reversed by MESNA treatment. Collagen contents of the liver tissue was increased by BDL (P < 0.001), and reversed back to the control levels with MESNA. Since MESNA administration alleviated the BDL-induced oxidative injury of the liver and improved the hepatic functions, it seems likely that MESNA with its antioxidant and antifibrotic properties, may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. (c) 2006 Published by Elsevier Ireland Ltd.Publication Metadata only Protective effects of resveratrol on hepatic ischemia reperfusion injury in streptozotocin-induced diabetic rats(SPRINGER, 2019) ELÇİOĞLU, HATİCE KÜBRA; Aktas, Hanife Serife; Ozel, Yahya; Ahmad, Sarfraz; Pence, Halime Hanim; Ayaz-Adakul, Betul; Kudas, Ilyas; Tetik, Sermin; Sekerler, Turgut; Canbey-Goret, Ceren; Kabasakal, Levent; Elcioglu, Hatice KubraResveratrol (RSV) is a natural polyphenolic compound having antioxidant effects. This study was designed to investigate the protective effects of resveratrol against oxidative stress in hepatic ischemia-reperfusion (I/R) injury in streptozotocin (STZ)-induced diabetic rats. STZ was injected intraperitonally (i.p.) to 18 Sprague-Dawley albino rats, which were divided into three groups, each having six rats. First group was non-treated diabetic group (D), second diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period (D + I/R), and third diabetic group was subjected to 30 min of hepatic ischemia followed by a 45-min reperfusion period and treated with 20 mg/kg/day oral RSV before 30 min I/R injury (D + I/R + RSV). At the end of the experimental period, animals were decapitated, and blood samples were collected to determine tissue tumor necrosis factor-alpha (TNF-alpha) levels. Liver and lung tissue samples were obtained for the evaluation of biochemical parameters including malondialdehyde (MDA) and glutathione (GSH) levels and histopathological examinations. Compared to control, I/R injury resulted in decreases in GSH levels and increases in MDA levels. Tissue TNF-alpha levels were also increased in the D + I/R group compared to D group. Treatment with RSV prevented the alterations on biochemical parameters and histopathological changes induced by I/R. We demonstrate that in diabetic rats, hepatic I/R injury is associated with an augmented inflammatory response and oxidative stress, while RSV pre-treatment significantly decreased these responses. Larger clinical studies are desirable to determine the exact role(s) of RSV on hepatic I/R injury among diabetic subjects.Publication Open Access BURDEN OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (MCRPC) IN TURKEY(ELSEVIER SCIENCE INC, 2016-11) KABASAKAL, LEVENT; Erdal, E.; Malhan, S.; Oksuz, E.; Benekli, M.; Cag, C.; Dane, F.; Kabasakal, L.; Kucuk, O.; Sozen, T. S.; Sar, C.; Kahveci, B.Publication Metadata only Burn-induced oxidative injury of the gut is ameliorated by the leukotriene receptor blocker montelukast(ELSEVIER SCI LTD, 2005) YEGEN, BERRAK; Kabasakal, L; Sener, G; Cetinel, S; Contuk, G; Gedik, N; Yegen, BCThere is increasing evidence that oxidative stress has an important role in the development of multiorgan failure after major burn injury. In the present study, we investigated whether the leukotriene receptor blocker montelukast is protective against burn-induced injury of the gut. Under brief ether anaesthesia, shaved dorsum of the rats was exposed to 90 degrees C (burn group) or 25 degrees C (control group) water bath for 10s. Montelukast (10mg/kg) or saline was administered intraperitoneally immediately after and at the 12th hour of the burn injury. Rats were decapitated 24 h after burn injury and the skin samples, as well as tissue samples from stomach, ileum and colon, were taken for the determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen contents. Tissues were also examined microscopically. Tumor necrosis factor-alpha (TNF-alpha) and lactate dehydrogenase (LDH) were assayed in serum samples. Severe skin scald injury (30% of total body surface area) caused a significant decrease in GSH level, which was accompanied with significant increases in MDA level, MPO activity and collagen content of tissues. Similarly, serum TNF-a and LDH were elevated in the burn group as compared to control group. On the other hand, montelukast treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by thermal trauma. Findings of the present study suggest that montelukast possesses an anti-inflammatory effect on burn-induced gastrointestinal damage and protects against oxidative injury by a neutrophil-dependent mechanism. (c) 2005 Elsevier Ltd. All rights reserved.