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ÜSTÜNOVA, SAVAŞ

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ÜSTÜNOVA
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    Effects of Angiotensin IV on Learning-Memory and Hippocampal Oxidative Stress in Diabetic Rats
    (2019-12-01T00:00:00Z) KILIÇ, Aysu; ÜSTÜNOVA, SAVAŞ; ELİBOL, BİRSEN; Bulut, Huri; MERAL, İSMAİL; Sahin, Emine Gulderen; KILIÇ, AYSU; ÜSTÜNOVA, SAVAŞ; ELİBOL, BİRSEN; BULUT, HURI; MERAL, İSMAİL
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    Hexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart
    (2013-07-01T00:00:00Z) Gurel, Ebru; Ustunova, SAVAŞ; Kapucu, Aysegul; Yilmazer, Nadim; EERBEEK, Otto; NEDERLOF, Rianne; HOLLMANN, Markus W.; Demirci-Tansel, Cihan; ZUURBIER, Coert J.; ÜSTÜNOVA, SAVAŞ
    Diabetes mellitus (DM) has been reported to alter the cardiac response to ischemia-reperfusion (IR). In addition, cardioprotection induced by ischemic preconditioning (IPC) is often impaired in diabetes. We have previously shown that the subcellular localisation of the glycolytic enzyme hexokinase (HK) is causally related to IR injury and IPC protective potential. Especially the binding of HK to mitochondria and prevention of HK solubilisation (HK detachment from mitochondria) during ischemia confers cardioprotection. It is unknown whether diabetes affects HK localisation during IR and IPC as compared to non-diabetes. In this study we hypothesize that DM alters cellular trafficking of hexokinase in response to IR and IPC, possibly explaining the altered response to IR and IPC in diabetic heart. Control (CON) and type I diabetic (DM) rat hearts (65 mg/kg streptozotocin, 4 weeks) were isolated and perfused in Langendorff-mode and subjected to 35 min I and 30 min R with or without IPC (3 times 5 min I). Cytosolic and mitochondrial fractions were obtained at (1) baseline, i.e. after IPC but before I, (2) 35 min I, (3) 5 min R and (4) 30 min R. DM improved rate-pressure product recovery (RPP; 71 +/- A 10 % baseline (DM) versus 9 +/- A 1 % baseline (CON) and decreased contracture (end-diastolic pressure: 24 +/- A 8 mmHg (DM) vs 77 +/- A 4 mmHg (CON)) after IR as compared to control, and was associated with prevention of HK solubilisation at 35 min I. IPC improved cardiac function in CON but not in DM hearts. IPC in CON prevented HK solubilisation at 35 min I and at 5 min R, with a trend for increased mitochondrial HK. In contrast, the non-effective IPC in DM was associated with solubilisation of HK and decreased mitochondrial HK at early reperfusion and a reciprocal behaviour at late reperfusion. We conclude that type I DM significantly altered cellular HK translocation patterns in the heart in response to IR and IPC, possibly explaining altered response to IR and IPC in diabetes.
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    PublicationOpen Access
    Effects of Cichorium Intybus on GABAA Receptors and Apoptosis in Pentyleneterazole-PTZ Kindling in Rats.
    (2021-08-01T00:00:00Z) Meral, İsmail; Eşrefoğlu, Mukaddes; Kara, Mehmet; Erkeç, Özlem Ergül; Tok, Olgu Enis; Armağan, Metin; MERAL, İSMAİL; EŞREFOĞLU, MUKADDES; ÜSTÜNOVA, SAVAŞ
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    PublicationOpen Access
    Hydrogen Sulphide and Nitric Oxide Cooperate in Cardioprotection Against Ischemia/Reperfusion Injury in Isolated Rat Heart
    (2020-09-01T00:00:00Z) ÜSTÜNOVA, SAVAŞ; TAKIR, SELÇUK; YILMAZER, NADİM; Bulut, Huri; ALTINDİREK, Didem; HATIRNAZ NG, Özden; Tansel, Cihan Demirci; Dogan, B. Sonmez Uydes; ÖZBEK, Uğur; ARMUTAK, Elif İlkay; Gurevin, Ebru Gurel; ÜSTÜNOVA, SAVAŞ
    Background/Aim: This study was designed to provide further evidence for the interactions between hydrogen sulfide (H2S) and nitric oxide (NO) in ischemia/reperfiision (I/R) injury. Materials and Methods: Rat hearts were studied with the Langendorff technique using the H2S donor sodium hydrosulfide (NaHS, 40 mu M) and the cystathionine gamma-lyase (CTH or CSE) inhibitor DL-propargylglycine (PAG, 1 mM). NO synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 30 mg/kg, 7 days) was administered before the isolation. The hearts were homogenized for biochemical and molecular analysis. Results: NaHS reversed I/R-induced cardiac performance impairment, increased tissue nitric oxide production and decreased tissue markers for cardiac injury, while L-NAME inhibited these effects. The expression of CTH was increased with PAG, which was suppressed by L-NAME. Conclusion: H2S and NO increase each other-s production suggesting their interaction and cooperation in cardioprotection against I/R injury.
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    Effects of Nigella sativa on apoptosis and GABA(A) receptor density in cerebral cortical and hippocampal neurons in pentylenetetrazol induced kindling in rats
    (2016-01-01) AYDIN, M. S.; USTUNOVA, SAVAŞ; ESREFOGLU, MUKADDES; MERAL, I.; Arifoglu, YASİN; DEMIRTAS, M.; MERAL, İSMAİL; EŞREFOĞLU, MUKADDES; ÜSTÜNOVA, SAVAŞ; ARİFOĞLU, YASİN
    We investigated the effects of Nigella sativa on apoptosis and gamma-aminobutyric acid (GABA(A)) receptor density in cerebral cortical and hippocampal neurons in a pentylenetetrazol (PTZ)-induced kindling model in rats. The PTZ kindling model was produced by injecting PTZ in subconvulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22 and 24 of the study into animals of PTZ treated (PTZ) and PTZ + N. sativa treated (PTZ + NS) groups. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the PTZ + NS group were treated also with a 10 mg/kg methanolic extract of N. sativa 2 h before each PTZ injection. Rats in the control group were treated with 4 ml/kg saline. The number of neurons that expressed GABA(A) receptors in the hippocampus and cerebral cortex of rats in the PTZ and PTZ + NS groups increased significantly. There was no significant difference in the number of GABA(A) receptors between the PTZ and PTZ + NS groups. GABA(A) receptor density of the neurons in the cerebral cortex, but not hippocampus, was increased in PTZ group compared to controls. We observed a significant increase in the number of apoptotic neurons in the cerebral cortex of rats of both the PTZ and PTZ + NS groups compared to controls. We observed a significant decrease in the number of the apoptotic neurons in the cerebral cortex of rats in the PTZ + NS group compared to the PTZ group. N. sativa treatment ameliorated the PTZ induced neurodegeneration in the cerebral cortex as reflected by neuronal apoptosis and neuronal GABA(A) receptor frequency.
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    Herbal Haemorrhoidal Cream for Haemorrhoids
    (2013-10-31T00:00:00Z) Gurel, Ebru; Ustunova, SAVAŞ; Ergin, Bulent; Tan, Nur; Caner, Metin; Tortum, Osman; Demirci-Tansel, Cihan; ÜSTÜNOVA, SAVAŞ
    Although hemorrhoids are one of the most common diseases in the world, the exact etiology underlying the development of hemorrhoids is not clear. Many different ointments are currently used to treat hemorrhoids; however, there is little evidence of the efficacy of these treatments to support their use. The aim of this study was to compare different herbal creams used for the treatment of hemorrhoids. Twenty-eight male Wistar albino rats, 6-8 weeks old and weighing 160-180 g, were used in this study as 1-control, 2-croton oil, 3-croton oil+fig leaves+artichoke leaves+walnut husks and 4-croton oil+fig leaves+artichoke leaves+walnut husks+horse chestnut fruit. After 3 days of croton oil application, rats were treated with 0.1 ml of cream or saline twice a day for 15 days by syringe. Tissue and blood samples were collected for histological, immunohistochemical and biochemical studies. Statistical significance was determined using one-way ANOVA followed by Tukey-s multiple comparison tests. Croton oil administration resulted in severe inflammation. The third group showed partial improvement in inflammation; however, the greatest degree of improvement was seen in the fourth group, and some recovered areas were observed. Myeloperoxidase immunoreactivity was found to be decreased in the third and fourth groups compared to the second group. Additionally, biochemical analyses (Myeloperoxidase, Malondyaldehyde, nitrate/nitrite and nitrotyrosine levels and Superoxide Dismutase activity) were in agreement with the histological and immunohistochemical results. In conclusion, croton oil causes inflammation in the anal area and results in hemorrhoids. Treatment with our herbal hemorrhoid creams demonstrated anti-inflammatory and anti-oxidant effects in this model.
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    PublicationOpen Access
    Angiotensin IV improves spatial memory in streptozotocin-induced diabetic rats by reducing oxidative stress and altering BDNF levels
    (2021-01-01T00:00:00Z) KILIÇ, AYSU; ÜSTÜNOVA, SAVAŞ; ELİBOL, BİRSEN; Bulut, Huri; MERAL, İSMAİL; Sahin, Gulderen; KILIÇ, AYSU; ÜSTÜNOVA, SAVAŞ; ELİBOL, BİRSEN; MERAL, İSMAİL
    In this study, we investigated the protective effects of angiotensin IV (Mg IV) on cognitive function in streptozotocin (STZ)-induced diabetic rats. Male Wistar albino rats, were randomly divided into four groups; control (C), diabetes (Dia, 60 mg/kg, STZ, i.p.), Mg IV (5 mu g/kg, s.c.) and Dia+Ang W. The passive avoidance and Morris water maze (MWM) tests were used to evaluate learning and memory performance. Behavioral tests were carried out between 21 and 30 days after the initial Ang IV injection. Hippocampi were dissected and retained for biochemical and Western blot analysis. The Dia group exhibited the poorest behavioral results, while the Dia+Ang W group performed highest on the MWM task. Superoxide dismutase, glutathione peroxidase, and malondialdehyde levels increased significantly in the Dia group compared to Dia+Ang IV. Brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartate levels were significantly elevated, while levels of GABA(A) significantly decreased, in the Dia+Ang IV group compared to the Dia group. These findings suggest that peripheral administration of Ang IV ameliorated spatial memory in diabetic rats by decreasing hippocampal oxidative stress and BDNF levels.
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    The Effects of Therapeutic Intermittent Hypoxia Implementation on Complete Blood Count Parameters: An Experimental Animal Model
    (2022-12-01T00:00:00Z) KILIÇ, TALHA; ŞENGÖR, MUSTAFA; ÜSTÜNOVA, SAVAŞ; KILIÇ, AYSU; DAŞKAYA, HAYRETTİN; YILDIZ ÖZER, AYSEL; ÜSTÜNOVA, SAVAŞ; KILIÇ, AYSU; DAŞKAYA, HAYRETTİN
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    Effect of Thymoquinone on Ischemia/Reperfusion Injury in Isolated Hearts of Streptozotocin-Induced Diabetic Rats
    (2019-12-01T00:00:00Z) ÜSTÜNOVA, SAVAŞ; KILIÇ, Aysu; Bulut, Hun; MERAL, İSMAİL; Alican, Inci; ÜSTÜNOVA, SAVAŞ; KILIÇ, AYSU; MERAL, İSMAİL
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    The Effects of Cichorium intybus Extract on Cerebellar Apoptosis and Oxidative Stress in Pentylenetetrazole-induced Kindling Model in Rats
    (2016-09-01) Meral, Ismail; Gurevin, Ebru Gurel; Ustunova, SAVAŞ; DEMIRTAS, Murat; Ozturk, Nilgun; Kiyan, Hulya Tuba; Armutak, Elif Ilkay; Sogut, Ibrahim; Erkeç, Özlem Ergül; MERAL, İSMAİL; ÜSTÜNOVA, SAVAŞ