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Böbrek iskemi ve reperfüzyon hasarında kreatin monohidrat desteğinin etkileri

Yıl 2023, Cilt: 28 Sayı: 1, 56 - 65, 20.01.2023
https://doi.org/10.21673/anadoluklin.1132144

Öz

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.

Destekleyen Kurum

Başkent Üniversitesi Tıp Fakültesi

Proje Numarası

DA18/11

Teşekkür

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

Kaynakça

  • Hong X, Zhao X, Wang G, Zhang Z, Pei H, Liu Z. Luteolin treatment protects against renal ischemia-reperfusion injury in rats. Mediators Inflamm. 2017;2017:9783893.
  • Nishida T, Hayashi T, Inamoto T, et al. Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury. Transplant Proc. 2018;50(1):250-8.
  • Wang P, Isaak CK, Siow YL, O K. Downregulation of cystathionine β-synthase and cystathionine γ-lyase expression stimulates inflammation in kidney ischemia-reperfusion injury. Physiol Rep. 2014;2(12):e12251.
  • Massberg S, Messmer K. The nature of ischemia/reperfusion injury. Transplant Proc. 1998;30(8):4217–23.
  • Nomura A, Zhang M, Sakamoto T, et al. Anti-inflammatory activity of creatine supplementation in endothelial cells in vitro. Br J Pharmacol. 2003;139(4):715-20.
  • Souza WM, Heck TG, Wronski EC, Ulbrich AZ, Boff E. Effects of creatine supplementation on biomarkers of hepatic and renal function in young trained rats. Toxicol Mech Methods. 2013;23(9):697–701.
  • Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review. Clin J Sport Med. 1998;8(4):298-304.
  • Jäger R, Purpura M, Shao A, Inoue T, Kreider RB. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. Amino Acids. 2011;40(5):1369-83.
  • Ferreira LG, De Toledo Bergamaschi C, Lazaretti-Castro M, Heilberg IP. Effects of creatine supplementation on body composition and renal function in rats. Med Sci Sports Exerc. 2005;37(9):1525-9.
  • Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem Biophys Res Commun. 2002;290(1):47–52.
  • Olsen S, Aagaard P, Kadi F, et al. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol. 2006;573(Pt 2):525-534.
  • Tarnopolsky MA. Creatine as a therapeutic strategy for myopathies. Amino Acids. 2011;40(5):1397–407.
  • Ipsiroglu OS, Stromberger C, Ilas J, Höger H, Mühl A, Stöckler-Ipsiroglu S. Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species. Life Sci. 2001;69(15):1805–15.
  • Helvacioglu F, Kandemir E, Karabacak B, et al. Effect of Creatine on Rat Sciatic Nerve Injury: A Comparative Ultrastructural Study. Turk Neurosurg. 2018;28(1):128-36.
  • Sestili P, Martinelli C, Colombo E, et al. Creatine as an antioxidant. Amino Acids. 2011;40(5):1385-96.
  • Wietzikoski EGG, Foiatto JC, Czeczko NG, et al. Tadalafil protector effect during ischemia-reperfusion in rats. Acta Cir Bras. 2017;32(11):973-83.
  • Zhou W, Farrar CA, Abe K, et al. Predominant role for C5b-9 in renal ischemia/reperfusion injury. J Clin Invest. 2000;105(10):1363-71.
  • Fidan PA, Helvacioglu F, Dagdeviren A. Intussusceptive growth of vascular bed in human placenta. Gazi Med J. 2019;30(3):246–51.
  • Wang L, Wei J, Jiang S, et al. Effects of different storage solutions on renal ischemia tolerance after kidney transplantation in mice. Am J Physiol Renal Physiol. 2018;314(3):F381-7.
  • Giraud S, Thuillier R, Codas R, et al. The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study. Int J Mol Sci. 2018;19(2):454.
  • Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277–85.
  • Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103–11.
  • Aydogdu N., Kaymak K. Yalçın Ö. Sıçanlarda Böbrek İskemi/ Reperfüzyon Hasarında N- Asetilsisteinin Etkileri. Fırat Tıp Dergisi. 2005;10(4):151–5.
  • Wang HJ, Varner A, Aboushwareb T, Atala A, Yoo JJ. Ischemia/reperfusion-induced renal failure in rats as a model for evaluating cell therapies. Ren Fail. 2012;34(10):1324–32.
  • Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011;17(11):1391-401.
  • Philipponnet C, Aniort J, Garrouste C, Kemeny JL, Heng AE. Ischemia reperfusion injury in kidney transplantation: A case report. Medicine (Baltimore). 2018;97(52):e13650.
  • Ishani A, Xue JL, Himmelfarb J, et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol. 2009;20(1):223-8.
  • Lo LJ, Go AS, Chertow GM, et al. Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int. 2009;76(8):893-9.
  • Zager RA, Johnson AC, Becker K. Acute unilateral ischemic renal injury induces progressive renal inflammation, lipid accumulation, histone modification, and “end-stage” kidney disease. Am J Physiol Renal Physiol. 2011;301(6):F1334-45.
  • de Bragança AC, Volpini RA, Mehrotra P, Andrade L, Basile DP. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury. Physiol Rep. 2016;4(13):e12829.
  • Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull. 2004;70:71–86.
  • Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17(6):1503–20.
  • Basile DP, Yoder MC. Renal endothelial dysfunction in acute kidney ischemia reperfusion injury. Cardiovasc Hematol Disord Drug Targets. 2014;14(1):3-14.
  • Woolfson RG, Millar CGM, Neild GH. Ischaemia and reperfusion injury in the kidney: Current status and future direction. Nephrol Dial Transplant. 1994;9(11):1529–31.
  • Gong DJ, Wang L, Yang YY, Zhang JJ, Liu XH. Diabetes aggravates renal ischemia and reperfusion injury in rats by exacerbating oxidative stress, inflammation, and apoptosis. Ren Fail. 2019;41(1):750–61.
  • Ozturk H, Cetinkaya A, Duzcu SE, Tekce BK, Ozturk H. Carvacrol attenuates histopathogic and functional impairments induced by bilateral renal ischemia/reperfusion in rats. Biomed Pharmacother. 2018;98:656-61.
  • Bircan B, Çakır M, Kırbağ S, Gül HF. Effect of apelin hormone on renal ischemia/reperfusion induced oxidative damage in rats. Ren Fail. 2016;38(7):1122–8.
  • Zhang J, Zou YR, Zhong X, et al. Erythropoietin pretreatment ameliorates renal ischaemia-reperfusion injury by activating PI3K/Akt signalling. Nephrology (Carlton). 2015;20(4):266-72.
  • Meyer LE, Machado LB, Santiago AP, et al. Mitochondrial creatine kinase activity prevents reactive oxygen species generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling activity. J Biol Chem. 2006;281(49):37361-71.
  • Clarke H, Hickner RC, Ormsbee MJ. The Potential Role of Creatine in Vascular Health. Nutrients. 2021;13(3):857.
  • Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev. 2015;4(2):20-7.
  • Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53(2):161-76.
  • Barbieri E, Guescini M, Calcabrini C, et al. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity. Oxid Med Cell Longev. 2016;2016:5152029.
  • Rahimi R. Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. J Strength Cond Res. 2011;25(12):3448-3455.
  • Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999;31(8):1108–10.
  • Metzl JD, Small E, Levine SR, Gershel JC. Creatine use among young athletes. Pediatrics. 2001;108(2):421-5.
  • Baracho NC, Castro LP, Borges Nda C, Laira PB. Study of renal and hepatic toxicity in rats supplemented with creatine. Acta Cir Bras. 2015;30(5):313-8.
  • Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements Lancet.1998;351:1252–3.
  • Taes YE, Delanghe JR, Wuyts B, van de Voorde J, Lameire NH. Creatine supplementation does not affect kidney function in an animal model with pre-existing renal failure. Nephrol Dial Transplant. 2003;18(2):258-64.
  • Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux M. Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Med Sci Sports Exerc. 2005;37(10):1717-20.
  • Nasseri A, Jafari A. Effects of creatine supplementation along with resistance training on urinary formaldehyde and serum enzymes in wrestlers. J Sports Med Phys Fitness. 2016;56(4):458-64.

Effects of creatine monohydrate supplementation in renal ischemia and reperfusion injury

Yıl 2023, Cilt: 28 Sayı: 1, 56 - 65, 20.01.2023
https://doi.org/10.21673/anadoluklin.1132144

Öz

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.

Proje Numarası

DA18/11

Kaynakça

  • Hong X, Zhao X, Wang G, Zhang Z, Pei H, Liu Z. Luteolin treatment protects against renal ischemia-reperfusion injury in rats. Mediators Inflamm. 2017;2017:9783893.
  • Nishida T, Hayashi T, Inamoto T, et al. Dual Gas Treatment With Hydrogen and Carbon Monoxide Attenuates Oxidative Stress and Protects From Renal Ischemia-Reperfusion Injury. Transplant Proc. 2018;50(1):250-8.
  • Wang P, Isaak CK, Siow YL, O K. Downregulation of cystathionine β-synthase and cystathionine γ-lyase expression stimulates inflammation in kidney ischemia-reperfusion injury. Physiol Rep. 2014;2(12):e12251.
  • Massberg S, Messmer K. The nature of ischemia/reperfusion injury. Transplant Proc. 1998;30(8):4217–23.
  • Nomura A, Zhang M, Sakamoto T, et al. Anti-inflammatory activity of creatine supplementation in endothelial cells in vitro. Br J Pharmacol. 2003;139(4):715-20.
  • Souza WM, Heck TG, Wronski EC, Ulbrich AZ, Boff E. Effects of creatine supplementation on biomarkers of hepatic and renal function in young trained rats. Toxicol Mech Methods. 2013;23(9):697–701.
  • Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review. Clin J Sport Med. 1998;8(4):298-304.
  • Jäger R, Purpura M, Shao A, Inoue T, Kreider RB. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. Amino Acids. 2011;40(5):1369-83.
  • Ferreira LG, De Toledo Bergamaschi C, Lazaretti-Castro M, Heilberg IP. Effects of creatine supplementation on body composition and renal function in rats. Med Sci Sports Exerc. 2005;37(9):1525-9.
  • Lawler JM, Barnes WS, Wu G, Song W, Demaree S. Direct antioxidant properties of creatine. Biochem Biophys Res Commun. 2002;290(1):47–52.
  • Olsen S, Aagaard P, Kadi F, et al. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. J Physiol. 2006;573(Pt 2):525-534.
  • Tarnopolsky MA. Creatine as a therapeutic strategy for myopathies. Amino Acids. 2011;40(5):1397–407.
  • Ipsiroglu OS, Stromberger C, Ilas J, Höger H, Mühl A, Stöckler-Ipsiroglu S. Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species. Life Sci. 2001;69(15):1805–15.
  • Helvacioglu F, Kandemir E, Karabacak B, et al. Effect of Creatine on Rat Sciatic Nerve Injury: A Comparative Ultrastructural Study. Turk Neurosurg. 2018;28(1):128-36.
  • Sestili P, Martinelli C, Colombo E, et al. Creatine as an antioxidant. Amino Acids. 2011;40(5):1385-96.
  • Wietzikoski EGG, Foiatto JC, Czeczko NG, et al. Tadalafil protector effect during ischemia-reperfusion in rats. Acta Cir Bras. 2017;32(11):973-83.
  • Zhou W, Farrar CA, Abe K, et al. Predominant role for C5b-9 in renal ischemia/reperfusion injury. J Clin Invest. 2000;105(10):1363-71.
  • Fidan PA, Helvacioglu F, Dagdeviren A. Intussusceptive growth of vascular bed in human placenta. Gazi Med J. 2019;30(3):246–51.
  • Wang L, Wei J, Jiang S, et al. Effects of different storage solutions on renal ischemia tolerance after kidney transplantation in mice. Am J Physiol Renal Physiol. 2018;314(3):F381-7.
  • Giraud S, Thuillier R, Codas R, et al. The Optimal PEG for Kidney Preservation: A Preclinical Porcine Study. Int J Mol Sci. 2018;19(2):454.
  • Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277–85.
  • Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103–11.
  • Aydogdu N., Kaymak K. Yalçın Ö. Sıçanlarda Böbrek İskemi/ Reperfüzyon Hasarında N- Asetilsisteinin Etkileri. Fırat Tıp Dergisi. 2005;10(4):151–5.
  • Wang HJ, Varner A, Aboushwareb T, Atala A, Yoo JJ. Ischemia/reperfusion-induced renal failure in rats as a model for evaluating cell therapies. Ren Fail. 2012;34(10):1324–32.
  • Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011;17(11):1391-401.
  • Philipponnet C, Aniort J, Garrouste C, Kemeny JL, Heng AE. Ischemia reperfusion injury in kidney transplantation: A case report. Medicine (Baltimore). 2018;97(52):e13650.
  • Ishani A, Xue JL, Himmelfarb J, et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol. 2009;20(1):223-8.
  • Lo LJ, Go AS, Chertow GM, et al. Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int. 2009;76(8):893-9.
  • Zager RA, Johnson AC, Becker K. Acute unilateral ischemic renal injury induces progressive renal inflammation, lipid accumulation, histone modification, and “end-stage” kidney disease. Am J Physiol Renal Physiol. 2011;301(6):F1334-45.
  • de Bragança AC, Volpini RA, Mehrotra P, Andrade L, Basile DP. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury. Physiol Rep. 2016;4(13):e12829.
  • Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull. 2004;70:71–86.
  • Devarajan P. Update on mechanisms of ischemic acute kidney injury. J Am Soc Nephrol. 2006;17(6):1503–20.
  • Basile DP, Yoder MC. Renal endothelial dysfunction in acute kidney ischemia reperfusion injury. Cardiovasc Hematol Disord Drug Targets. 2014;14(1):3-14.
  • Woolfson RG, Millar CGM, Neild GH. Ischaemia and reperfusion injury in the kidney: Current status and future direction. Nephrol Dial Transplant. 1994;9(11):1529–31.
  • Gong DJ, Wang L, Yang YY, Zhang JJ, Liu XH. Diabetes aggravates renal ischemia and reperfusion injury in rats by exacerbating oxidative stress, inflammation, and apoptosis. Ren Fail. 2019;41(1):750–61.
  • Ozturk H, Cetinkaya A, Duzcu SE, Tekce BK, Ozturk H. Carvacrol attenuates histopathogic and functional impairments induced by bilateral renal ischemia/reperfusion in rats. Biomed Pharmacother. 2018;98:656-61.
  • Bircan B, Çakır M, Kırbağ S, Gül HF. Effect of apelin hormone on renal ischemia/reperfusion induced oxidative damage in rats. Ren Fail. 2016;38(7):1122–8.
  • Zhang J, Zou YR, Zhong X, et al. Erythropoietin pretreatment ameliorates renal ischaemia-reperfusion injury by activating PI3K/Akt signalling. Nephrology (Carlton). 2015;20(4):266-72.
  • Meyer LE, Machado LB, Santiago AP, et al. Mitochondrial creatine kinase activity prevents reactive oxygen species generation: antioxidant role of mitochondrial kinase-dependent ADP re-cycling activity. J Biol Chem. 2006;281(49):37361-71.
  • Clarke H, Hickner RC, Ormsbee MJ. The Potential Role of Creatine in Vascular Health. Nutrients. 2021;13(3):857.
  • Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev. 2015;4(2):20-7.
  • Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53(2):161-76.
  • Barbieri E, Guescini M, Calcabrini C, et al. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity. Oxid Med Cell Longev. 2016;2016:5152029.
  • Rahimi R. Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. J Strength Cond Res. 2011;25(12):3448-3455.
  • Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. 1999;31(8):1108–10.
  • Metzl JD, Small E, Levine SR, Gershel JC. Creatine use among young athletes. Pediatrics. 2001;108(2):421-5.
  • Baracho NC, Castro LP, Borges Nda C, Laira PB. Study of renal and hepatic toxicity in rats supplemented with creatine. Acta Cir Bras. 2015;30(5):313-8.
  • Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements Lancet.1998;351:1252–3.
  • Taes YE, Delanghe JR, Wuyts B, van de Voorde J, Lameire NH. Creatine supplementation does not affect kidney function in an animal model with pre-existing renal failure. Nephrol Dial Transplant. 2003;18(2):258-64.
  • Poortmans JR, Kumps A, Duez P, Fofonka A, Carpentier A, Francaux M. Effect of oral creatine supplementation on urinary methylamine, formaldehyde, and formate. Med Sci Sports Exerc. 2005;37(10):1717-20.
  • Nasseri A, Jafari A. Effects of creatine supplementation along with resistance training on urinary formaldehyde and serum enzymes in wrestlers. J Sports Med Phys Fitness. 2016;56(4):458-64.
Toplam 51 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm ORJİNAL MAKALE
Yazarlar

Fatma Helvacıoğlu 0000-0002-6026-0045

Tayfun Göktaş 0000-0002-6727-3084

Hande Ozge Altunkaynak-camca 0000-0002-4547-7756

Tuğçe Şirinoğlu 0000-0003-0364-0401

Proje Numarası DA18/11
Yayımlanma Tarihi 20 Ocak 2023
Kabul Tarihi 14 Ekim 2022
Yayımlandığı Sayı Yıl 2023 Cilt: 28 Sayı: 1

Kaynak Göster

Vancouver Helvacıoğlu F, Göktaş T, Altunkaynak-camca HO, Şirinoğlu T. Böbrek iskemi ve reperfüzyon hasarında kreatin monohidrat desteğinin etkileri. Anadolu Klin. 2023;28(1):56-65.

13151 This Journal licensed under a CC BY-NC (Creative Commons Attribution-NonCommercial 4.0) International License.