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Öğe Antioxidant enzyme activities, lipid peroxidation, and total antioxidant status in children with Henoch-Schonlein purpura(Springer, 2008) Ece, Aydin; Kelekci, Selvi; Kocamaz, Halil; Hekimoglu, Askin; Balik, Hasan; Yolbas, Ilyas; Erel, OzcanThe aim of this study was to assess the role of oxidative stress in the pathogenesis of Henoch-Schonlein purpura (HSP) vasculitis. The activities of catalase (CAT), arylesterase (ARYL), and paraoxonase (PON) as antioxidant enzymes and serum malondialdehyde (MDA) level as an indicator of lipid peroxidation, together with total antioxidant status (TAS), were measured in 29 children with HSP (mean age 9.3 +/- 2.7 years), both at the onset of the disease and at the remission period and in matched controls. Active-stage HSP had significantly higher MDA level (15.5 +/- 7.3 vs 7.8 +/- 3.9 nmol/l, respectively, P<0.001) and lower TAS (524 +/- 122 vs 699 +/- 122 mu mol Trolox Equiv/1, P< 0.001), PON (97 +/- 47 vs 136 +/- 95 U/1, P=0.042), ARYL (158 +/- 39 vs 212 +/- 52 U/1, P<0.001), and CAT (50 +/- 27 vs 69 +/- 20 U/1, P=0.002) activities compared with the control subjects. Although CAT (P>0.05) and PON (P>0.05) activities were found to be similar between active and remission stages of HSP, the active stage of the disease had significantly lower ARYL (P=0.011) and TAS (P=0.006) and higher MDA (P<0.001) values compared with remission period. Significant positive correlations were found between CAT and MDA (r=0.433, P=0.019) and between CAT and C-reactive protein (r=0.386, P=0.035) in the active stage of HSP. No significant differences were detected in oxidant/antioxidant parameters between patients with or without renal, gastrointestinal, or joint involvement (P>0.05). Increased oxidative stress and lipid peroxidation may play important roles in the pathogenesis of HSP vasculitis. Antioxidant therapeutic interventions in longlasting vasculitis and risk of atherosclerosis secondary to increased oxidant stress remain to be investigated.Öğe The contribution of nitric oxide on the relaxation effects of diethylstilbestrol(Saudi Med J, 2008) Hekimoglu, Askin; Celik, Fatma; Tas, Taskin; Ece, Aydin; Kavak, VatanObjectives: To evaluate the contribution of nitric oxide (NO) on the relaxation effects of diethylstilbestrol on rat uterus. Methods: Uterine rings from 8 nonpregnant Wistar Albino rats (300-350g) in the pro-estrous phase were suspended in an organ bath and electrical field stimulation applied for recording isometric tension. The influence of NO on contractile responses of rat uterine rings was investigated. The effects of NO precursor L-arginine (10(-7)-10(-4)M) concentration and NO synthase inhibitor L-nitro-arginine-methyl ester (10(-7)-10(-4)M) concentration and a combination of them on contractile responses were studied in the presence and absence of diethylstilbestrol (2x10(-4)M) concentration. The study was carried out at the Department of Pharmacology Laboratory, Faculty of Medicine, Dicle University, Diyarbakir, Turkey. Results: Totally, 30 samples were investigated (n=6 for each group, 5 groups). Diethylstilbestrol inhibited contractile responses 64.2 +/- 4.5% (n=6, p<0.05). Contractile responses decreased in the presence of Larginine (n=6, p<0.05) and this inhibition was abolished in the presence of L-nitro-arginine-methyl ester (n=6, p<0.05). The inhibition on contractile responses to diethylstilbestrol was potentiated in the presence of Larginine under similar conditions (n=6, p<0.05). The contractile responses to electrical field stimulation in the presence of diethylstilbestrol were not affected by L-nitro-arginine-methyl ester (n=6, p>0.05). Conclusions: These data provide evidence that NO may potentiate the inhibitory effects of diethylstilbestrol by different mechanisms on the electrically induced contractions of the non-pregnant rat uterus.Öğe Effect of melatonin on epididymal sperm quality after testicular ischemia/reperfusion in rats(Elsevier Science Inc, 2010) Kurcer, Zehra; Hekimoglu, Askin; Aral, Faruk; Baba, Fusun; Sahna, EnginObjective: To determine the effect of melatonin, a pineal secretory product that prevents testicular ischemia/reperfusion (IR) injury through its antioxidative properties, on epididymal sperm quality in a rat testicular IR injury model. Design: Experimental study. Setting: University pharmacology laboratory. Animal(s): Fifty-six 8-week-old male Wistar albino rats. Intervention(s): Left testicular artery and vein occluded for I hour; before the bilateral orchiectomy, the organ was allowed to reperfuse 30 days. Melatonin (10 mg/kg IP) or vehicle (1% ethanol in saline) was administrated for 10 minutes before reperfusion and for 1 hour after reperfusion. Main Outcome Measure(s): After 24 hours of reperfusion, the rats were decapitated, and the testicular tissue samples were obtained for histologic examination. In addition, after 30 days of reperfusion, the epididymal sperm concentration, motility, and abnormal sperm rates were determined in the sperm collected from the epididymis. Result(s): A statistically significant decrease in sperm concentration resulted from IR as well as an increase in sperm abnormalities, but the sperm motility did not change. Melatonin treatment did not prevent the IR-induced reduction in sperm concentration. However, melatonin treatment statistically significantly decreased the sperm abnormalities when compared with the IR injured samples. Conclusion(s): Melatonin may improve sperm morphology for a protective effect in IR-induced testicular injury. (Fertil Steril (R) 2010;93:1545-9. (C)2010 by American Society for Reproductive Medicine.)Öğe Effects of 3-aminobenzamide on unilateral testicular ischemia-reperfusion injury: What is the role of PARP inhibition?(Canadian Science Publishing, 2010) Hekimoglu, Askin; Kurcer, Zehra; Aral, Faruk; Baba, Fusun; Atessahin, Ahmet; Sakin, FatihOn a examine les effets therapeutiques de l'inhibition de la poly(adenosine diphosphate-ribose) polymerase par le 3-aminobenzamide (3-AB) dans une lesion d'ischemie-reperfusion (I/R) des testicules en utilisant une analyse de sperme. On a effectue des examens histopathologiques et biochimiques pour mesurer les activites de la superoxyde dismutase (SOD), de la catalase (CAT), de la glutathion peroxydase (GSH-Px), et les taux de glutathion (GSH) reduit. On a divise des rats males en 3 groupes : ayant subi une operation factice (sham) (n = 12), I/R (n = 12) et I/R avec 3AB (I/R-3-AB) (n = 12). On a occlus l'artere testiculaire gauche pendant 1 h, puis on l'a soumis a une reperfusion pendant 24 h (pour les examens biochimiques et histopathologiques) et 30 jours (pour l'analyse de sperme). L'administration de 3-AB par voie intraperitoneale 10 min avant et 1 h apres la reperfusion a augmente la diminution induite par l'I/R de la motilite du sperme dans les 2 testicules, et elle a diminue l'augmentation anormale des taux de sperme dans le testicule ipsilateral. Toutefois, le traitement par 3-AB n'a pu prevenir la diminution induite par l'I/R du taux de sperme dans les 2 testicules. Les activites de SOD et de CAT sont demeurees stables chez tous les groupes. L'I/R a augmente l'activite de la GSH-Px et les taux de GSH. Le traitement par 3-AB a renverse l'augmentation induite par l'I/R de l'activite de la GSH-Px comme chez les sham, mais il n'a pas modifie les taux de GSH. Le traitement par 3-AB a augmente de maniere significative la diminution induite par l'I/R du score histopathologique. En conclusion, un traitement par 3-AB offre des avantages biochimiques et histopathologiques potentiels au-dela de la qualite du sperme et pourrait diminuer l'alteration de la torsion testiculaire.Öğe Effects of increasing ratio of progesterone in estrogen/progesterone combination on total oxidant/antioxidant status in rat uterus and plasma(Springer Heidelberg, 2010) Hekimoglu, Askin; Bilgin, Hakki Murat; Kurcer, Zehra; Ocak, Ali RizaThe relationship between increasing ratio of progesterone in estrogen/progesterone combination and oxidative stress (OS) was investigated. Thirty non-pregnant Wistar Albino female rats were divided into five groups and bilaterally ovariectomized (Ovx) except sham group. Sham + 0.3 cc seaseme oil, Ovx + 0.3 cc seaseme oil, Ovx + estradiol propionate (E2) (1 mu g/kg), Ovx + E2 + medroxyprogesterone acetate (MPA) 1 mg/kg, Ovx + E2 + MPA 20 mg/kg. Hormones were applied for three consecutive days after 28 days of ovariectomy. Their uteri and blood samples were collected and nitric oxide (NO), malondialdehyde (MDA), total oxidative status (TOS) and total antioxidant capacity (TAC) levels were determined. E2 + MPA1 treatment decreased NO, MDA and TOS levels and increased TAC levels in uterus. Plasma NO levels elevated in all groups and MDA production increased due to E2 treatment when compared to ovariectomy. E2 + MPA20 treatment increased TOS levels, while TAC levels decreased when compared to ovariectomy in plasma. Using E2 plus low dose progesterone may prevent pathologies resourced of OS.Öğe Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats(Taylor & Francis Ltd, 2015) Oguz, Elif; Yilmaz, Zehra; Ozbilge, Hatice; Baba, Fusun; Tabur, Suzan; Yerer, Mukerrem Betul; Hekimoglu, AskinWe investigated the changes in the serum levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, the pro-inflammatory cytokines, and the possible effect of melatonin on the modulation of these inflammatory molecules after renal ischemia reperfusion (IR). The study was carried out in the laboratory of Department of Pharmacology. Forty-six male Wistar albino rats were divided into five groups as control (n = 6), positive control (n = 4), sham (n = 12), renal IR (n = 12), and renal IR melatonin (n = 12). After 1 h renal pedicle occlusion, the blood samples were taken for the measurement of cytokine levels at second hour of the reperfusion. The rats were sacrificed after 24 h of reperfusion for histopathological evaluation. Melatonin or vehicle was administrated to IR rats. Lipopolysaccharide (LPS) was administered to the positive control group and the blood was taken at fourth hour. Serum TNF-alpha levels increased significantly in renal IR and LPS groups. Serum IL-6 levels were not different from control except the LPS group. There was no significant correlation between the serum TNF-alpha levels and the histopathological score after renal IR. Melatonin treatment reversed the increase of serum TNF-alpha levels and histopathological injury in renal tissue after renal IR. Melatonin may have a protective effect by reducing the serum level of TNF-alpha in renal IR.Öğe Effects of statins in an indomethacin-induced gastric injury model in rats(Aves, 2012) Ozbakis-Dengiz, Gunnur; Hekimoglu, Askin; Kandemir, Nilufer; Kurcer, ZehraBackground/aims: Statins have additional pleiotropic effects beyond their lipid-lowering effects. In this study, the effects of statins were evaluated in an indomethacin-induced gastric injury model in rats. Materials and Methods: Animals were divided into eight groups. Distilled water (control group), omeprazole (30 mg / kg), atorvastatin (20 and 40 mg 1 kg), simvastatin (20 and 40 mg 1 kg), and rosuvastatin (20 and 40 mg/kg) were given orally (gavage). Thirty minutes later, indomethacin (25 mg 1 kg) was administered orally to all groups. Six hours later, the animals were sacrificed by decapitation. The mean ulcer indexes for each group were calculated, and the stomachs were evaluated histopathologically. Results: The ulcer indexes were as follows: control 1.72 +/- 0.16, omeprazole 0 +/- 0.00, and atorvastatin, simvastatin and rosuvastatin (at 20 and 40 mg/kg doses, respectively) 4.28 +/- 0.39, 4.99 +/- 0.96, 1.72 +/- 0.73, 1.90 +/- 0.48, 1.85 +/- 0.26, and 1.67 +/- 0.18. Atorvastatin significantly increased the indomethacin-induced ulcer index at both doses and the erosion score at 40 mg/kg dose. Although the 20 mg/kg dose of simvastatin inhibited mononuclear leukocyte infiltration, the 40 mg/kg dose induced hyperemia. Rosuvastatin did not decrease mononuclear leukocyte or neutrophil infiltrations at 20 mg/kg dose, and only neutrophil infiltration at the 40 mg/kg dose. Conclusions: In patients with gastric discomfort, statins must be used carefully. If statin therapy is needed, we recommend to avoid using atorvastatin and to use the other statins only in the minimum effective dose.Öğe Lycopene, an Antioxidant Carotenoid, Attenuates Testicular Injury Caused by Ischemia/Reperfusion in Rats(Tohoku Univ Medical Press, 2009) Hekimoglu, Askin; Kurcer, Zehra; Aral, Faruk; Baba, Fuesun; Sahna, Engin; Atessahin, AhmetTesticular torsion is a common syndrome that could lead to infertility. We investigated the therapeutic effects of lycopene, an antioxidant caretenoid, on testicular ischemia/reperfusion (IR) injury that resembles testicular torsion. Male Wistar albino rats were divided into three groups: sham (n = 6), IR (n = 18), and ischemia/reperfusion with lycopene (IRL, n = 18). Left testicular artery and vein was occluded for 1 h, followed by reperfusion of 3 h, 24 h or 30 days in IR and IRL animals. Either corn oil (vehicle) or lycopene (4 mg/kg) was administrated once daily by gavage to IR or IRL animals, respectively, 5 min after ischemia. Sham-operated animals were treated with vehicle by gavage 5 min after the operation. IR decreased sperm motility and concentration in both ipsilateral and contralateral testes and increased abnormal sperm rate in ipsilateral testis after 30 days of reperfusion. Treatment with lycopene increased the motility in bilateral testes and decreased the rate of abnormal sperm in ipsilateral testis to the sham level, but did not increase sperm concentration in bilateral testes. IR increased the activities of catalase and glutathione peroxidase and the level of reduced glutathione by 24 h of reperfusion, but malondialdehyde remained unchanged. Lycopene treatment restored the enzyme activities but not the reduced glutathione level. Lycopene treatment also ameliorated the IR-induced tissue damage in bilateral testes. In conclusion, the therapeutic antioxidant effect of lycopene on germ cells could serve as a promising intervention to oxidative stress-associated infertility problems, such as testicular torsion.Öğe Neutrophil activation, protein oxidation and ceruloplasmin levels in children with Henoch-Schonlein purpura(Springer, 2007) Ece, Aydin; Kelekci, Selvi; Hekimoglu, Askin; Kocamaz, Halil; Balik, Hasan; Yolbas, Ilyas; Erel, OzcanThe aim of this study was to investigate the role of neutrophil activation, protein oxidation and ceruloplasmin (CLP) in the pathogenesis of Henoch-Schonlein purpura (HSP), which has not been investigated previously. Serum activities of myeloperoxidase (MPO) and arylesterase (ARYL) and levels of free thiol groups, CLP and total oxidant status (TOS) were measured in 29 children with HSP at the onset of the disease and during remission in comparison with 30 healthy subjects. Patients at active stage had significantly higher MPO activity (391 +/- 277 vs. 155 +/- 154 U/l, P<0.001), higher CLP (832 +/- 120 vs. 682 +/- 114 mg/dl, P<0.001) and TOS values (20.7 +/- 11.8 vs. 7.5 +/- 2.8 mu mol H2O2/l, P<0.001) than the controls, respectively. Patients had significantly lower ARYL activity (158x10(3) +/- 3x10(3) vs. 187x10(3) +/- 4 46x10(3) U/l, P<0.001) and lower free thiol levels (234 +/- 48 vs. 279 +/- 26 mu mol/l, P<0.001) than the controls, respectively. Significantly positive correlations were found between TOS and MPO (r=0.437, P=0.018) and TOS and CLP (r=0.409, P=0.028) at disease onset, whereas a negative correlation was found between MPO and thiol (r=-0.597, P=0.001) during remission. In conclusion, protein oxidation and neutrophil activation may play important roles in the pathogenesis of HSP. Further research is required to understand the potential linkage between oxidant stress and complications and to develop therapeutic strategies in HSP.