Özlem KARA, Tümay UMUROĞLU, Tolga GÜRSOY, KEMAL TOLGA SARAÇOĞLU, Fevzi Yılmaz GÖĞÜŞ

Sepsis oluşturulan sıçanlarda farklı konsantrasyonlarda verilen albuminin böbrek antioksidan ve serbest oksijen radikalleri üzerine etkisi

Amaç: Bu çalışmanın amacı sepsis oluşturulan sıçanlarda antioksidan özellikler gösteren albuminin farklı konsantrasyonlarının böbrek antioksidan düzeyleri ve böbrek fonksiyonları üzerine etkilerini araştırmaktır. Gereç ve Yöntem: Çalışmada 28 adet erişkin Sprague-Dawley sıçan 4 gruba ayrıldı. Birinci gruba (Grup K) herhangi bir ajan uygulanmadı. Diğer gruplarda intraabdominal sepsis oluşturuldu. İkinci gruba (Grup S) 90 dk süreyle 30 ml/kg serum fizyolojik infüzyonu, 3. gruba (Grup A5) 90 dk süreyle 15 ml/kg %5 albumin infüzyonu, 4. gruba (Grup A25) ise 45 dk süreyle 3 ml/kg %25 albumin infüzyonu uygulandı. 18. saatin sonunda tüm sıçanlara anestezi altında bilateral nefrektomi yapıldı. Kan üre nitrojeni, kreatinin ve albumin düzeylerini saptamak için böbrek venlerinden kan örnekleri alındı. Böbrek dokuları elektron mikroskobu altında diseke edilerek serbest oksijen radikalleri ve antioksidan düzeylerinin ölçümü yapıldı. Bulgular: Çalışmamızda serum fizyolojik uygulanan grupla karşılaştırıldığında her 2 konsantrasyonda albumin uygulanan septik sıçanlarda böbrek fonksiyonlarının daha iyi, glutatyon düzeylerinin daha yüksek, malondialdehit ve myeloperoksidaz düzeylerinin daha düşük olduğu saptandı. Ek olarak A25 grubunda kan üre nitrojeni ve böbrek glutatyon düzeyleri A5 grubuna göre belirgin yüksekti. Sonuç: Böbrek dokusunda antioksidan etkilerini saptadığımız %25 albuminin hızlı infüzyonunun sepsis olgularında kullanımının böbrek disfonksiyonu gelişmesini önleme veya geciktirme açısından yüz güldürücü olabileceği düşüncesine varılmıştır.

Anahtar Kelimeler:

Sepsis, Albumin, Oksijen radikalleri, Antioksidan ajanlar

-

Objectives: The aim of this study is to investigate the effects of different concentrations of albumin, which has antioxidant characteristics on renal antioxidant levels and renal functions in rats with sepsis.Materials and Methods: Twenty-eight adult male Sprague-Dawley rats were divided into 4 groups. No agent was implemented to Group K. Group S received 30 ml/kg of saline infusion for 90 min, Group A5 received 15 ml/kg of 5% albumin infusion for 90 min and Group A25 received 3 ml/kg of 25% albumin infusion for 45 min. At the end of the 18th hour, bilateral nephrectomy was performed. Blood samples were taken to determine blood urea nitrogen, creatinine and albumin levels. Kidney tissue samples were dissected to measure the levels of free oxygen radicals and antioxidants.Results: Better renal function, higher levels of glutathione and malondialdehyde with lower myeloperoxidase levels were obtained in septic rats following treatment with 2 different concentrations of albumin. In Group A25, blood urea nitrogen and renal glutathione levels were significantly higher than in Group A5. Conclusion: We are of the opinion that the rapid infusion of 25% albumin may prevent or delay the occurrence of renal dysfunction in patients with sepsis.

Keywords:

Sepsis, Albumin, Oxygen radicals, Antioxidants,

PDF

___

1. Chen YC, Chang SC, Pu C, Tang GJ. The impact of nationwide education program on clinical practice in sepsis care and mortality of severe sepsis: a population-based study in taiwan. PLoS One 2013;8:e77414. doi: 10.1371/journal.pone.0077414.
2. Trzeciak S, Cinel I, Phillip Dellinger R, et al. Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials. Acad Emerg Med 2008;15:399-413. doi: 10.1111/j.1553-2712.2008.00109.x.
3. Bozza FA, D’Avila JC, Ritter C, Sonneville R, Sharshar T, Dal-Pizzol F. Bioenergetics, mitochondrial dysfunction, and oxidative stress in the pathophysiology of septic encephalopathy. Shock 2013;39:10-6. doi: 10.1097/SHK.0b013e31828fade1.
4. Wang Z, Holthoff JH, Seely KA, et al. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsisinduced renal microcirculatory failure and acute kidney injury. Am J Pathol 2012;180:505-16. doi: 10.1016/j.ajpath.2011.10.011.
5. Sakaguchi S, Furusawa S. Oxidative stress and septic shock: metabolic aspects of oxygen-derived free radicals generated in the liver during endotoxemia. FEMS Immunol Med Microbiol 2006;47:167-77.
6. Rocha M, Herance R, Rovira S, Hernández-Mijares A, Victor VM. Mitochondrial dysfunction and antioxidant therapy in sepsis. Infect Disord Drug Targets 2012;12:161-78.
7. Lowes DA, Webster NR, Murphy MP, Galley HF. Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis. Br J Anaesth 2013;110:472-80. doi: 10.1093/bja/aes577.
8. Rozga J, Piątek T, Małkowski P. Human albumin: old, new, and emerging applications. Ann Transplant 2013;18:205-17. doi: 10.12659/AOT.889188.
9. Anraku M, Chuang VT, Maruyama T, Otagiri M. Redox properties of serum albumin. Biochim Biophys Acta 2013;1830:5465-72. doi: 10.1016/j.bbagen.2013.04.036.
10. Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology 2005;41:1211-9.
11. Cantin AM, Paquette B, Richter M, Larivée P. Albumin-mediated regulation of cellular glutathione and nuclear factor kappa B activation. Am J Respir Crit Care Med 2000;162:1539-46.
12. Garcovich M, Zocco MA, Gasbarrini A. Clinical use of albumin in hepatology. Blood Transfus 2009;7:268-77. doi: 10.2450/2008.0080- 08.
13. Jacob M, Chappell D, Conzen P, Wilkes MM, Becker BF, Rehm M. Small-volume resuscitation with hyperoncotic albumin: a systematic review of randomized clinical trials. Crit Care 2008;12:R34. doi: 10.1186/cc6812.
14. Powers KA, Kapus A, Khadaroo RG, et al. Twenty-five percent albumin prevents lung injury following shock/resuscitation. Crit Care Med 2003;31:2355-63.
15. Wei CI, Gilliam MC, Cohen MD, Cornell JA, Moazam F. A preliminary study of age-related difference in resistance to sepsis in the rat model. J Surg Res 1987;43:460-7.
16. Saracoglu KT, Saracoglu A, Umuroglu T, Ugurlu MU, Deniz M, Gogus FY. The preventive effect of dopamine infusion in rats with abdominal compartment syndrome. J Invest Surg 2013;26:334-9.
17. Saracoglu A, Saracoglu KT, Deniz M, Ercan F, Yavuz Y, Göğüş FY. Dopamine – a preventive agent for mesenteric ischemia and reperfusion injury in abdominal compartment syndrome. Adv Clin Exp Med 2011;20:613-21.
18. Das UN. n-3 fatty acids, γ-linolenic acid, and antioxidants in sepsis. Crit Care 2013;17:312. [Epub ahead of print].
19. Victor VM, Rocha M, De la Fuente M. Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol 2004;4:327-47.
20. Bae MJ, Ishii T, Minoda K, et al. Albumin stabilizes (-)-epigallocatechin gallate in human serum: binding capacity and antioxidant property. Mol Nutr Food Res 2009;53:709-15. doi: 10.1002/mnfr.200800274.
21. Schnell D, Camous L, Guyomarc’h S, et al. Renal perfusion assessment by renal Doppler during fluid challenge in sepsis. Crit Care Med 2013;41:1214-20. doi: 10.1097/CCM.0b013e31827c0a36.
22. Vanmassenhove J, Glorieux G, Hoste E, Dhondt A, Vanholder R, Van Biesen W. Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis. Crit Care 2013; 13;17:R234. doi:10.1186/cc13057. [Epub ahead of print].
23. Wang Z, Holthoff JH, Seely KA, et al. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsisinduced renal microcirculatory failure and acute kidney injury. Am J Pathol 2012;180:505-16. doi: 10.1016/j.ajpath.2011.10.011.
24. Krysztopik RJ, Matheson PJ, Spain DA, Garrison RN, Wilson MA. Lazaroid and pentoxifylline suppress sepsis-induced increases in renal vascular resistance via altered arachidonic acid metabolism. J Surg Res 2000;93:75-81.
25. Phakdeekitcharoen B, Boonyawat K. The added-up albumin enhances the diuretic effect of furosemide in patients with hypoalbuminemic chronic kidney disease: a randomized controlled study. BMC Nephrol 2012;13:92. doi: 10.1186/1471-2369-13-92.
26. Sehirli O, Sener E, Cetinel S, et al. Alpha-lipoic acid protects against renal ischaemia-reperfusion injury in rats. Clin Exp Pharmacol Physiol 2008;35:249–55.
27. Sibilia V, Rindi G, Pagani F, et al. Ghrelin protects against ethanolinduced gastric ulcers in rats: studies on the mech- anisms of action. Endocrinology 2003;144:353–9.
28. Gonzalez RJ, Moore EE, Ciesla DJ, Neto JR, Biffl WL, Silliman CC. Hyperosmolarity abrogates neutrophil cytotoxicity provoked by postshock mesenteric lymph. Shock 2002;18:29-32.
29. Cuschieri J, Gourlay D, Garcia I, Jelacic S, Maier RV. Hypertonic preconditioning inhibits macrophage responsiveness to endotoxin. J Immunol 2002;168:1389-96.
30. Choi P. Review: albumin increases mortality in critically ill patients. ACP J Club 2002;137:51.
31. Martin GS, Moss M, Wheeler AP, Mealer M, Morris JA, Bernard GR. A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med 2005;33:1681-7.