Böbrek iskemi ve reperfüzyon hasarında kreatin monohidrat desteğinin etkileri

Year 2023, Volume: 28 Issue: 1, 56 - 65, 20.01.2023

Fatma Helvacıoğlu Tayfun Göktaş Hande Ozge Altunkaynak-camca Tuğçe Şirinoğlu

https://doi.org/10.21673/anadoluklin.1132144

Abstract

Amaç; Böbrek nakli ya da cerrahi girişimler sırasında gelişebilen iskemi ve reperfüzyon hasarı etkisini hücrelerdeki enerji metabolizmasının bozulması ve oksidatif stresin artmasına yol açarak gösterir. Popüler sporcu destek ürünü olan kreatin monohidrat endojen bir bileşiktir. Hücrelerin enerji metabolizmasını etkileyerek oksidatif stresi azalttığı ve antioksidan etki gösterdiği bilinmektedir. Böbrekte deneysel olarak oluşturulan iskemi reperfüzyon hasarı sonrasında artan oksidatif strese ve yapısal düzeyde izlenen hasara karşı kreatin monohidratın olası etkisinin değerlendirilmesi hedeflenmiştir.

Yöntemler: Çalışmada Sprague Dawley (270-380 gr) türü 24 adet erkek sıçan kullanıldı. Sıçanlar rastgele dört gruba ayrıldı: Grup 1: Kontrol grubu, Grup 2: İskemi/ Reperfüzyon grubu, Grup 3: İskemi/ Reperfüzyon +Kreatin monohidrat (Kreatin 2 g/kg/gün), Grup 4: Kreatin monohidrat (2 g/kg/gün) olarak düzenlendi. Grup 2 ve Grup 3’teki sıçanlara intraperitoneal anestezi sonrası 45 dakika boyunca sol renal arterin klemplenmesiyle renal iskemi oluşturuldu ve 45. dk’nın sonunda klemp uzaklaştırıldıktan sonra sol böbreğin parlak kırmızı renge ulaşması reperfüzyonun sağlanması olarak kabul edilerek karın ön duvarı kapatıldı. Grup 3 ve Grup 4’deki sıçanlara 3 gün süresince kreatin monohidrat (2g/kg/gün) distile su içinde çözülerek gavaj yoluyla uygulandı. Reperfüzyondan 72 saat sonra genel anestezi altında kardiyak kan, sol böbrek dokuları alındıktan sonra sakrifiye edildiler. Böbrek dokuları ışık ve elektron mikroskopta değerlendirildi. Plazma örneklerinde total oksidan ve antioksidan stres parametreleri ölçümlendi.

Bulgular: İskemi ve reperfüzyon modelinde ince yapı düzeyinde glomerüler kapillerlerdeki belirgin eritrosit stazı saptandı. Bunun yanında glomerüller endotelin ve podositlerin hücre bütünlüğünün korunamadığı izlenirken proksimal tübüllerdeki hücrelerde de şişme sonucu tübül lümenin tıkandığı görüldü. Kreatin uygulanan gruplarda total antioksidan seviyesinin istatistiksel olarak anlamlı ölçüde artması yeniden yapılanma sürecinin pozitif yönde ilerlediğinin göstergesi olarak yorumlandı.

Sonuç: Sonuç olarak uygulanan yöntemden kaynaklandığı düşünülen eritrosit stazı nedeniyle dolaşımın tam olarak sağlanamadığı ve buna bağlı olarak kreatin monohidrat desteğinin yapısal düzeyde belirgin olumlu etki gösteremediği düşünüldü.

Keywords

Böbrek, elektron mikroskobu, iskemi-reperfüzyon hasarı

Supporting Institution

Başkent Üniversitesi Tıp Fakültesi

Project Number

DA18/11

Thanks

Dilasude Demirçinli, Özge Çelik, Yüsra Elif İnce, Cansu Adıgüzel, Elifnaz Ünal, Zeynep Ünal, Elnur Hasanov’a deney aşamasındaki katkılarından dolayı teşekkür ederiz.

Effects of creatine monohydrate supplementation in renal ischemia and reperfusion injury

Abstract

Aim: Ischemia and reperfusion injury, can occur during kidney transplantations surgery, showing their effects by disrupting cellular energy metabolism and increasing oxidative stress. Creatine monohydrate, a popular sport supplement, is an endogenous compound. It is known that it reduces oxidative stress through effecting the energy metabolism of cells and has an antioxidant effect. It was aimed to evaluate the possible effect of creatine monohydrate against the increased oxidative stress and structural damage mediated by experimentally induced renal ischemia-reperfusion injury in this study.

Methods: Twenty-four male Sprague Dawley (270-380 gr) rats were used in the study. Rats were randomly divided into four groups: Group-1: Control group, Group-2: Ischemia/Reperfusion group, Group-3: Ischemia / Reperfusion+ Creatine monohydrate (2g/kg/day), Group-4: Creatine monohydrate (2g/kg/day). After anesthesia, a midline abdominal incision was performed in the related groups and renal ischemia was induced by clamping left renal artery during 45 min. At the end of ischemia the non-traumatic clamp was removed and kidney reperfusion was noted as return of blush color. Afterward, abdominal posterior wall was closed. Creatine monohydrate (2 g/kg/day) was dissolved in distilled water and given to the rats with oral gavage in Group-3 and Group-4 for 3 days After 72 hours of reperfusion, cardiac blood and left kidney tissues were taken under general anesthesia and they were sacrificed. Kidney tissues were evaluated by light and electron microscopy. Total antioxidant and oxidant stress parameters were also measured in the plasma samples.

Results: In the ischemia and reperfusion model, significant erythrocyte stasis was detected in the glomerular capillaries at ultrastructural level. In addition, it was observed that the integrity of the glomerular endothelial cells and podocytes could not be preserved, while the tubule lumen was occluded as a result of the swelling of epithelial cells. The statistically significant increase in the total antioxidant level in the creatine administered groups was interpreted as an indicator of the positive progress of the remodeling process.

Conclusion: As a result, it was observed that creatine monohydrate supplementation did not show a significant beneficial effect a structural level, since the circulation could not be fully restored due to erythrocyte stasis caused by the procedure.

Keywords

Electron microscopy, ischemia-reperfusion injury, kidney

Project Number

DA18/11

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