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PEKER EYÜBOĞLU, İREM

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PEKER EYÜBOĞLU

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2016 - 201932020 - 20233
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Author: YEGEN, BERRAK × Start date: 2012 ×

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Now showing 1 - 6 of 6
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    Deneysel sepsis modelinde akut kardiyopulmoner ve serebral hasarda nöropeptit W'nin etkisi
    (2019-12-13) ATICI, ALİ EMRE; PEKER EYÜBOĞLU, İREM; YEGEN, BERRAK; AKKİPRİK, MUSTAFA; ERCAN, FERİHA; ATICI A. E., ARABACI TAMER S., levent h. n., PEKER EYÜBOĞLU İ., ERCAN F., AKKİPRİK M., YEGEN B.
    Giriş ve Amaç: Ciddi enfeksiyonların neden olduğu sepsis ve beraberinde görülen çoklu organ yetmezliği, yüksek morbidite ve mortalite oranıyla en önemli klinik sendromlardan biridir. Yakın zamanda tanımlanan ve nöroendokrin düzenlemelerde işlev gördüğü gösterilen nöropeptit W (NPW)’nin, deneysel sepsis modeli oluşturularak akciğer, kalp ve beyin dokularında indüklenen oksidatif hasarda olası tedavi edici etkilerini araştırmayı amaçladık. Yöntemler: Ketamin anestezisi altında, Sprague-Dawley erkek sıçanlarda sham-operasyon (n=8) yapıldı veya çekal ligasyon ve perforasyon ile sepsis oluşturuldu (n=64). Post-operatif ciltaltına 3 doz (hemen sonra, 12. ve 24. saatlerde) serum fizyolojik (SF) veya TNF-alfa inhibitörü + antibiyotik (1 mg/kg etanersept + 100 mg/kg seftriakson) veya NPW (0,1; 0,3; 1, 3 ve 10 g/kg) uygulanırken, sham-opere gruba SF enjeksiyonları yapıldı. Yirmibeşinci saatte alınan kan örneklerinde C-reaktif protein (CRP), kortikosteron ve IL-6 düzeyleri ile çıkarılan akciğer, kalp ve beyin dokularında antioksidan glutatyon, lipit peroksidasyonunu gösteren malondialdehit ile nükleer faktör kappa-B (NF- B) mRNA ekspresyon düzeyleri ölçüldü. Hematoksilen-eozin ile histopatolojik değerlendirmeler yapıldı. Verilerin analizinde ANOVA ve Student’ın t-testleri kullanıldı. Bulgular: Etanersept+antibiyotik veya NPW (1-10 g/kg) tedavili sepsis gruplarında IL6, kortikosteron ve CRP düzeyleri SF-tedavili sepsis grubuna göre düşük bulundu (p<0,05-0,001). SFsepsis grubunda beyinde ve akciğerde malondialdehit düzeylerinin arttığı (p<0,01) ve glutatyonun düştüğü (p<0,01) gözlendi. Etanersept+antibiyotik tedavisi veya NPW beyindeki bu değişiklikleri engelledi (p<0,05-0,001). Buna karşın, akciğerde sepsisle artan malondialdehit ve azalan glutatyon düzeylerine antibiyotik+etanersept etkili olmazken, NPW (0,1-0,3 g/kg) akciğerde malondialdehit düzeyini düşürdü (p<0,05-0,01). Kalp dokusunda ölçülen malondialdehit ve glutatyon düzeyleri ile tüm dokularda ölçülen NF- B ekspresyonları açısından gruplar arasında anlamlı fark bulunmadı. SF-tedavili sepsis grubunda gözlenen dejenere nöron sayısında artış, akciğerde şiddetli kanama, alveoler yapıda bozulma ve nötrofil infiltrasyonu ile kardiyomiyositlerdeki konjesyon ve orta derecede hasar gibi değişikliklerin etanersept+antibiyotik ve NPW (10 g/kg) ile hafiflediği ve histolojik yapıların neredeyse normale döndüğü izlendi. Sonuç: Sepsisin ilk 24 saatinde uygulanan NPW, doza bağımlı olarak akciğer ve beyinde oksidatif hasara karşı koruyucu etki göstermektedir.
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    Neuropeptide w alleviates hepatorenal oxidative damage in sepsis-induced rats
    (2020-05-01) ATICI, ALİ EMRE; PEKER EYÜBOĞLU, İREM; ERCAN, FERİHA; AKKİPRİK, MUSTAFA; YEGEN, BERRAK; ATICI A. E., ARABACI TAMER S., levent h. n., PEKER EYÜBOĞLU İ., ERCAN F., AKKİPRİK M., YEGEN B.
    Background: Despite modern surgical, medical and intensive care treatments, sepsis is still one of the most frequent causes of morbidity and mortality due to multiple life-threatening organ dysfunctions. We aimed to investigate the possible protective effect of neuropeptide W (NPW), a novel peptide effective in regulating neuroendocrine functions, against sepsisinduced hepatorenal damage. Methods: In male Sprague-Dawley rats (200–250 g), sepsis was induced by cecal ligation and puncture under ketamine anesthesia (n=48). Immediately after surgery, saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) plus antibiotic (ceftriaxon; 100 mg/kg) (ET+C) or NPW (0.1, 0.3, 1 or 3 mg/kg) was given subcutaneously, and repeated at 12th and 24th hours, while sham-operated control group (n=8) received three saline injections within twenty-four hours. Rats were decapitated at the 25th hour of surgery and C-reactive protein (CRP), corticosterone and IL-6 levels were measured in serum samples. Kidney and liver samples were obtained for the measurement of myeloperoxidase activity (MPO), malondialdehyde and glutathione levels and nuclear factor kappa-B (NF-kB) mRNA expression levels. Histopathological evaluations were performed in hematoxylin-eosin-stained samples. ANOVA and Student's t-tests were used for data analysis. Results: Elevated serum levels of IL-6, corticosterone and CRP (p<0.05-0.01) in saline-treated sepsis group, as compared to controls, were depressed in the ET+C- (p<0.05) or NPW- (p<0.05-0.001) treated groups. Hepatic malondialdehyde and MPO levels, which were increased in salinetreated sepsis group (p<0.05 and p<0.001), were decreased by ET+C- (p<0.01) or NPW (p<0.05-0.001) treatments. Similarly, increased renal malondialdehyde level was depressed by NPW (p<0.05), but not by ET+C; while none of the treatments had an inhibitory effect on renal MPO. In contrast to replenished renal glutathione levels by all treatments, hepatic glutathione content was not changed by any of the treatments. Hepatic and renal NF-kB mRNA expressions were similar in all groups. Severe hepatocyte degeneration, sinusoidal congestion and inflammatory cell infiltration were observed in saline-treated sepsis group, while parenchymal degeneration, congestion and Kupffer cell activation were mild in ET+Cand NPW-treated sepsis groups. Similarly, severe degeneration of renal corpuscles and tubules with glomerular and interstitial congestion in the saline-treated sepsis group was replaced by moderate glomerular and interstitial vascular congestion and mild tubular congestion in both NPW- and ET+C-treated groups. Conclusion: NPW, applied during the first 24 hours of sepsis, exerted a dose-dependent protective effect against hepatorenal damage, which appears to involve an inhibitor
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    Investigation of biphosphonate and melatonin combine treatment on bone formation/resorption rate and morphology in a rat model of osteoporosis
    (2016-09-01) PEKER EYÜBOĞLU, İREM; YEGEN, BERRAK; AKKİPRİK, MUSTAFA; ERCAN, FERİHA; GÜRLER E. B., PEKER EYÜBOĞLU İ., çilingir kaya ö. T., AKKİPRİK M., ERCAN F., YEGEN B.
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    Alpha-7 nicotinic receptor agonist GTS-21 ameliorates contrast-induced nephropathy in rats
    (2019-10-05) AKÇAY, SEÇKİN; ÖZDEMİR KUMRAL, ZARİFE NİGAR; PEKER EYÜBOĞLU, İREM; YEGEN, BERRAK; AKÇAY S., ÖZDEMİR KUMRAL Z. N., çilingir kaya ö. T., PEKER EYÜBOĞLU İ., AKKİPRİK M., YEGEN B.
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    Phoenixin-14 alleviates remote organ injury in bile duct ligation induced cholestatic liver injury and acute pancreatitis in rats
    (2023-09-14) KAHRAMAN, MERVE MERİÇ; ERCAN, FERİHA; ERZİK, CAN; PEKER EYÜBOĞLU, İREM; YÜKSEL, MERAL; YEGEN, BERRAK; ŞEN L. S., KAHRAMAN M. M., Sezen Mermer K., koroğlu k., ERCAN F., ERZİK C., PEKER EYÜBOĞLU İ., YÜKSEL M., İMERYÜZ N., YEGEN B.
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    Neuropeptide-w protects against stress-induced gastric ulcer in rats via the involvement of capsaicin-sensitive vagal afferent fibers
    (2020-11-28) PEKER EYÜBOĞLU, İREM; AKKİPRİK, MUSTAFA; YEGEN, BERRAK; AKAKIN, DİLEK; ARABACI TAMER S., AKBULUT S., AKAKIN D., PEKER EYÜBOĞLU İ., AKKİPRİK M., YEGEN B.
    AIM: Neuropeptide-W (NPW), expressed in hypothalamus and peripheral organs, activates hypothalamus-pituitary-adrenal axis, and may have a physiological role in neuroendocrine response to stress. The aim was to evaluate protective effects of NPW on stress-induced gastric injury in rats. METHODS: Sprague-Dawley male rats were fasted for 24 hours, restrained and immersed in water-bath for 6 h to induce water-immersion restraint stress (WIRS), and NPW (0.1 or 5µg/kg) or saline was injected subcutaneously at 15 minutes before WIRS (n=24), while saline-injected control rats had no WIRS (n=8). For degeneration of vagal afferent fibers (VAD), in some rats (n=24) capsaicin (1%) was applied perivagally under ketamine anesthesia, and 3 weeks later WIRS was induced. Using a laser Doppler, gastric serosal blood flow was monitored under anesthesia. Following cardiac puncture, gastric tissues were removed for macroscopic/microscopic scoring and measurement of myeloperoxidase activity, malondialdehyde and glutathione levels. Gastric NF-κB and cerebral NPW mRNA expressions were detected by RT-PCR. One-way ANOVA was used for statistical analysis. RESULTS: WIRS decreased mean serosal blood flow, resulted in elevated macroscopic/ microscopic scores compared to control group (p<0.001), while myeloperoxidase activity and malondialdehyde level were elevated (p<0.05) and antioxidant glutathione was depleted (p<0.001). WIRS depressed gastric NF-κB and cerebral NPW mRNA expressions (p<0.01). Neither doses of NPW changed gastric NF-κB mRNA. Lowerdose of NPW elevated blood flow (p<0.001), abolished WIRS-induced elevations in myeloperoxidase and malondialdehyde levels (p<0.05). High-dose NPW replenished gastric glutathione and brain NPW expression and reduced scores (p<0.05-0.01). Despite that VAD did not alter effects of high-dose NPW, reductions in malondialdehyde and myeloperoxidase, and improvement in blood flow by low-dose NPW were abolished by VAD (p<0.05). CONCLUSION: In stress-induced oxidative gastric injury, NPW provides gastroprotection by improving depressed blood flow and inhibiting ulcer-induced oxidative injury, which involve contribution of vagal afferent fibers