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    Beta-Hydroxy-Beta-Methyl-Butyrate, L-glutamine, and L-arginine supplementation improves Radiation-Induce acute intestinal toxicity
    (Taylor and Francis Ltd, 2019) Yavaş, Çağdaş; Yavaş, Güler; Çelik, Esin; Büyükyörük, Ahmet; Büyükyörük, Cennet; Yüce, Deniz; Ata, Özlem
    We aimed to evaluate effects of ?-hydroxy-?-methylbutyrate, L-glutamine, and L-arginine (HMB/GLN/ARG) on radiation-induced acute intestinal toxicity. Forty rats were divided into four groups: group (G) 1 was defined as control group, and G2 was radiation therapy (RT) control group. G3 and G4 were HMB/GLN/ARG control and RT plus HMB/GLN/ARG groups, respectively. HMB/GLN/ARG started from day of RT and continued until the animals were sacrificed 10 days after RT. The extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis were quantified on histological sections of intestinal mucosa. Statistical analyses were performed using the analysis of variance (ANOVA) test. There were significant differences between study groups regarding extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis and crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis (p values were 0.019 for fibrosis, <.001 for the others). Pair-wise comparisons revealed significant differences regarding surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, vascular dilatation, and congestion between G2 and G4 (p values were <.001,.033, <.001,.007, and <.001, respectively). Fibrosis score was significantly different only between G1 and G2 (p =.015). Immunohistochemical TGF-? score of G2 was significantly higher than G1 and G3 (p values were.006 and.017, respectively). There was no difference between TGF-? staining scores of G2 and G4. Concomitant use of HMB/GLN/ARG appears to ameliorate radiation-induced acute intestinal toxicity; however, this finding should be clarified with further studies. © 2018, © 2018 Taylor & Francis Group, LLC.
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    The impact of spironolactone on the lung injury induced by concomitant trastuzumab and thoracic radiotherapy
    (IJRR-IRANIAN JOURNAL RADIATION RES, 2019) Yavaş, Güler; Yavaş, Çağdaş; Çelik, Esin; Şen, E.; Ata, O.; Afşar, Rengin Elsürer
    Background: To evaluate impact of spironolactone (S) on pulmonary toxicity of concomitant use of thoracic radiotherapy (RT) and trastuzumab (T). Materials and Methods: Eighty rats were divided into eight groups: group (G) 1 was control group; G2, G3 and G4 were RT, S and T groups; G5, G6, G7 and G8 were RT+T, T+S, RT+S and RT+T+S groups respectively. Rats were sacrificed at 6 hour, 21 and 100 day after RT and lung samples were retrieved. Results: By 100th days of RT inflammation score, lung fibrosis score and TGF- expression were significantly different within study groups (p values were 0.002, 0.001 and 0.043 respectively). Inflammation score of G8 was significantly lower than inflammation scores of G2 and G5 (p values: G2-G8=0.004, and G5-G8=0.022). Inflammation score of G2 was significantly higher than G7 (p=0.028). There were significant differences regarding to fibrosis scores between G2-G8 (p=0.015), G2-G7 (p=0.017) and G5-G8 (p=0.011). TGF-beta expression was higher in both G2 and G5 when compared to G8 (p = 0.038). Conclusion: Our results suggested that S is an effective treatment option for improving radiation-induced pulmonary fibrosis. These findings should be clarified with further preclinical and clinical studies.
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    Prophylactic ozone administration reduces renal ischemia-reperfusion injury in the rat
    (E-CENTURY PUBLISHING CORP, 2016) Kal, Öznur; Akıllıoğlu, İshak; Kal, Ali; Çelik, Esin; Yılmaz, Mustafa; Önal, Merih; Önal, Özkan
    Background: The objective of this study was to examine the role of ozone oxidative preconditioning after renal IR (ischemia reperfusion) injury. Methods: Twenty-eight Wistar rats were randomized into four groups: sham operated (S), IR, ozone (O), and O+IR. The S group was administered physiological saline (PS) intraperitoneally (i.p.) for seven days. The IR group was subjected to renal ischemia for 1 h by occlusion of the left renal artery and vein, followed by reperfusion for 2 h. The O group was administered ozone i.p. for seven days. In the O+IR group, ozone was administered i.p. for seven days before the IR procedure. IR injury (as in the IR group) was induced on the eight day. Laboratory analyses of renal tissue samples for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were performed. Results: The total oxidant score (TOS) and total antioxidant capacity (TAC) of the blood samples were also analyzed. The degree of renal injury was highest in the IR group. In the O+IR group, renal injury was decreased. The antioxidant parameters were increased in the O group. The oxidant parameters were highest in the IR group. Conclusion: Ozone preconditioning ameliorated renal IR injury, with a significant decrease observed in the renal IR injury score.
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    The protective effect of prophylactic ozone administration against retinal ischemia-reperfusion injury
    (TAYLOR & FRANCIS LTD, 2017) Kal, Ali; Kal, Öznur; Akıllıoğlu, İshak; Çelik, Esin; Yılmaz, Mustafa; Gönül, Şaban; Solmaz, Merve
    Introduction: Retinal ischemia-reperfusion (IR) injury is associated with many ocular diseases. Retinal IR injury leads to the death of retinal ganglion cells (RGCs), loss of retinal function and ultimately vision loss. The aim of this study was to show the protective effects of prophylactic ozone administration against retinal IR injury.Materials and methods: A sham group (S) (n=7) was administered physiological saline (PS) intraperitoneally (i.p.) for 7 d. An ischemia reperfusion (IR) group (n=7) was subjected to retinal ischemia followed by reperfusion for 2h. An ozone group (O) (n=7) was administered 1mg/kg of ozone i.p. for 7 d. In the ozone+IR (O+IR) group (n=7), 1mg/kg of ozone was administered i.p. for 7 d before the IR procedure and at 8 d, the IR injury was created (as in IR group). The rats were anesthetized after second hour of reperfusion and their intracardiac blood was drawn completely and they were sacrificed. Blood samples were sent to a laboratory for analysis of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total oxidant score (TOS) and total antioxidant capacity (TAC). The degree of retinal injury was evaluated according to changes in retinal cells and necrotic and apoptotic cells using the TUNEL method. Data were evaluated statistically with the Kruskal-Wallis test.Results: The number of RGCs and the inner retinal thickness were significantly decreased after ischemia, and treatment with ozone significantly inhibited retinal ischemic injury. In the IR group, the degree of retinal injury was found to be the highest. In the O+IR group, retinal injury was found to be decreased in comparison to the IR group. In the ozone group without retinal IR injury, the retinal injury score was the lowest. The differences in the antioxidant parameters SOD, GSH-Px and TAC were increased in the ozone group and the lowest in the IR group. The oxidant parameters MDA and TOS were found to be the highest in the IR group and decreased in the ozone group.Discussion: IR injury is also positively correlated with the degree of early apoptosis. This study demonstrated that ozone can attenuate subsequent ischemic damage in the rat retina through triggering the increase of the antioxidant capacity.
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    Spironolactone Ameliorates the Cardiovascular Toxicity Induced by Concomitant Trastuzumab and Thoracic Radiation Therapy
    (ELSEVIER SCIENCE INC, 2016) Yavaş, Güler; Çelik, Esin; Yavaş, Çağdaş; Elsürer, Çağdaş; Afşar, Rengin Elsürer
    [Abstract not Available]
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    Spironolactone ameliorates the cardiovascular toxicity induced by concomitant trastuzumab and thoracic radiotherapy
    (ELSEVIER, 2017) Yavaş, Güler; Çelik, Esin; Yavaş, Çağdaş; Elsürer, Çağdaş; Afşar, Rengin Elsürer
    Aim: We aimed to evaluate impact of spironolactone (S) on cardiovascular toxicity of concomitant use of radiotherapy (RT) and trastuzumab (T). Background: S, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. S ameliorates anthracycline-induced cardiotoxicity, there is no data regarding to effect of S on both T and radiation-induced cardiotoxicity. Materials/Methods: Eighty rats were divided into eight groups: group (G) 1 was defined as control group. G2, G3 and G4 were RT, S and T groups respectively. G5, G6, G7 and G8 were RT + T, T + S, RT + S and RT + T + S groups respectively. Rats were sacrificed at 6th hour; 21st and 100th days after RT. Heart and thoracic aorta samples were taken for microscopical examination. Results: Cardiac inflammation and fibrosis scores and; TGF-8 expression were not significantly different within study groups at 6th hour and 21st days of RT. By 100th days of RT fibrosis scores and TGF-expression in cardiac samples were significantly different between study groups (p values were 0.004 and 0.002 respectively). Pair-wise comparisons revealed that both cardiac fibrosis scores and TGF-8 expression levels were higher in G5 when compared to G8 (p values were 0.046 and 0.028 respectively). Moreover the TGF-8 expression was higher in G5 when compared to G2 (p =0.046). We could not demonstrate any significant differences with respect to inflammation, fibrosis and TGF-8 expression in thoracic aorta samples between study groups. Conclusions: Although S had a protective effect on cardiac tissue it had no protective effect on thoracic aorta when administered with RT + T. (C) 2017 Greater Poland Cancer Centre. Published by Elsevier Sp. z o.o. All rights reserved.