Oxytocin Effect on Sepsis-induced Experimental Rat Renal Failure Model: A Histological and Biochemical study
Öz
We aimed to investigate the therapeutic role of Oxytocin
(OT) in sepsis induced rats and its effects on kidneys. Sepsis was induced in 24 of them by cecal ligation-perforation
(CLP) method. One of the groups of CLP did not recieve any treatment while
either saline 1 ml/kg or OT 0.4 mg/kg was applied intraperitoneally to the
other groups within the first hour of surgery. 8 rats were sham-operated and 8
rats were spared as control group. Plasma TNF-α, CRP, MDA levels, total
antioxidant capacity (TAC), creatinine level and peripheral leukocyte (WBC)
counts were measured. TNF-α, CRP, MDA levels and WBC counts were significantly
increased in CLP and CLP-saline groups, on the contrary they are decreased in
CLP-OT group. Histopathologically loss of brush border, tubular dilatation and
mononuclear cell infiltration was significantly decreased in CLP-OT group but
there was no significant difference in erytrocyte extravasation and cast
formation when compared to CLP and CLP-saline groups. Our results indicate that
OT may have a therapeutic value in limiting sepsis induced inflammation and
organ damage.
Anahtar Kelimeler
Kaynakça
- 1. Surbatovic M., Radakovic S., Jovanovic K., Romić P. New strategies in multiple organ dysfunction syndrome therapy for sepsis. Srpski arhiv za celokupno lekarstv 133, 7-8: 379-83, 2005.
- 2. Ulloa L., Doody J., Massagué J. Inhibition of TGFb/SMAD signal transduction by the INFg/STAT pathway. Nature 397, 6721: 710-12, 1999.
- 3. Riedemann N.C., Guo R.F., Ward P.A. Novel strategies for the treatment of sepsis. Nature Medicine 9: 517-24, 2003.
- 4. Van der Poll T., Lowry S. F. Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?, Shock 3, 1: 1-12, 1995.
- 5. Salvemini D., Cuzzocrea S. Oxidative stress in septic shock and disseminated intravascular coagulation. Free Radical Biology & Medicine 33, 8: 1173-85, 2002.
- 6. Huang W., Lee S. L., Sjöquist M. Natriuretic role of endogenous oxytocin in male rats infused with hypertonic NaCl. American Journal of Physiology 268, 3: 634-40, 1995.
- 7. Petty M.A, Lang R.E, Unger T, Ganten D. The cardiovascular effects of oxytocin in conscious male rats. European Journal of Pharmacology 112, 2: 203-10, 1985.
- 8. Gimpl G., Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiological Review 81, 2: 629-83, 2001.
- 9. Petersson M., Lundeberg T., Sohlström A., Wiberg U., Uvnas-Moberg K. Oxytocin increases the survival of musculocutaneous flaps. Naunyn-Schmiedeberg's Archives of Pharmacology 81:701-4, 1998.
- 10. Petersson M., Wiberg U., Lundeberg T., Uvnas-Moberg K. Oxytocin decreases carrageenan induced inflammation in rats. Peptides 22, 9: 1479-84, 2001.
- 11. Iseri S. O., Sener G., Saglam B., Gedik N., Ercan F.,. Yegen B. C. Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. Journal of Surgical Research 126, 1: 73–81, 2005.
- 12. Demougeot C., Marie C., Beley A. Importance of iron location in iron-induced hydroxyl radical production by brain slices. Life Science 67, 4: 399-410, 2000.
- 13. Benzie I. F., Strain J. J. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods in Enzymology 299:15-27, 1999.
- 14. Angus D.C., Wax R.S. Epidemiology of sepsis: an update. Critical Care Medicine, 29: 109-16, 2001.
- 15. Guha M., Mackman N. LPS induction of gene expression in human monocytes. Cell Signal, 13,2: 85-94, 2001.
- 16. Gutierrez-Ramos J.C, Bluethmann H. Molecules and mechanisms operating in septic shock: Lessons from knockout mice. Immunology Today 18, 7: 329-34, 1997.
- 17. Gitto E., Karbownik M., Reiter R.J,. Tan D. X, Cuzzocrea S., Chiurazzi P., Cordaro S., Corona G., Trimarchi G., Barberi I. Effects of melatonin treatment in septic newborns. Pediatric Research 50, 6: 756-60, 2001.
- 18. Spangelo B.L., De Holl P.D, Kalabay L., Bond B.R., Arnaud P. Neurointermediate pituitary lobe cells synthesize and release IL-6 in vitro: effects of lipopolysaccharide and IL-1 beta. Endocrinology, 135, 2: 556-63, 1994.
- 19. Williams K.I., El Tahir K.E. Effects of uterine stimulant drugs on prostacyclin production by the pregnant rat myometrium. I. Oxytocin, bradykinin and PGF2 alpha. Prostaglandins 19, 1: 31-8, 1980.
- 20. Pavlova E.L., Lilova M.I., Savou V. M. Oxidative stres in children with kidney disease. Pediatric Nephrology 19: 1599-1604, 2005.
- 21. Fridovich I. Forefronts in nephrology: summary of the newer aspects of renal cell injury. Kidney International 42, 3: 523-39, 1992.
- 22. Biyikli N.K., Tuğtepe H., Sener G., Velioğlu-Ogunç A., Cetinel S., Midillioğlu S., Gedik N., Yeğen B.C. Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides 27, 9: 2249-57, 2006.
- 23. Tuğtepe H., Sener G., Biyikli N.K., Yüksel M., Cetinel S., Gedik N., Yeğen B.C. The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regulatory Peptites 2007;140 (3):101–108, 2007.
Sepsis Kaynaklı Deneysel Sıçan Böbrek Hasarı Modeli Üzerine Oksitosin Etkisi: Histolojik ve Biyokimyasal Bir Çalışma
Öz
Bu çalışmada, sepsis ile indüklenen sıçanlarda
oksitosinin (OT) terapatik rolü ve bunun böbrekler üzerindeki etkisi
araştırılmıştır. 24 adet sıçanda çekal ligasyon-perforasyon (CLP) yöntemi ile
sepsis oluşturulmuştur. Cerrahi girişimin ilk saati içerisinde, CLP oluşturulan
gruplarından birine herhangi bir tedavi uygulanmamış diğer gruba 1 ml/kg salin
ve 0.4 mg/kg OT intraperitoneal olarak uygulanmıştır. 8 sıçan sham opere, 8
sıçan da kontrol grubu olarak ayrılmıştır. Plazmada TNF-α, CRP, MDA düzeyleri,
toplam antioksidan kapasite (TAK), kreatinin seviyesi ve periferik lökosit
(WBC) sayıları ölçülmüştür. CLP ve CLP-salin gruplarında TNF-α, CRP, MDA
düzeyleri ve WBC sayılarında anlamlı artma saptanırken CLP-OT grubunda anlamlı
düşüş görülmüştür. CLP ve CLP-salin gruplarıyla kıyaslandığında; CLP-OT
grubunda serum MDA, CRP ve WBC seviyeleri anlamlı olarak düşerken, TAC anlamlı
derecede yüksek çıkmıştır. CLP-OT gruplarında, histopatolojik olarak fırçamsı
kenar kaybı, tübüler dilatasyon ve mononükleer hücre infiltrasyonu anlamlı
düzeyde azalmıştır. Ancak, CLP ve CLP-salin grupları karşılaştırıldığında
ekstravazasyon ve kast bulguları açısından anlamlı fark bulunamamıştır.
Sonuçlar, OT'nin sepsis kaynaklı inflamasyon ve organ hasarı açısından terapotik
değeri olabileceğini göstermektedir.
Anahtar Kelimeler
Kaynakça
- 1. Surbatovic M., Radakovic S., Jovanovic K., Romić P. New strategies in multiple organ dysfunction syndrome therapy for sepsis. Srpski arhiv za celokupno lekarstv 133, 7-8: 379-83, 2005.
- 2. Ulloa L., Doody J., Massagué J. Inhibition of TGFb/SMAD signal transduction by the INFg/STAT pathway. Nature 397, 6721: 710-12, 1999.
- 3. Riedemann N.C., Guo R.F., Ward P.A. Novel strategies for the treatment of sepsis. Nature Medicine 9: 517-24, 2003.
- 4. Van der Poll T., Lowry S. F. Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense?, Shock 3, 1: 1-12, 1995.
- 5. Salvemini D., Cuzzocrea S. Oxidative stress in septic shock and disseminated intravascular coagulation. Free Radical Biology & Medicine 33, 8: 1173-85, 2002.
- 6. Huang W., Lee S. L., Sjöquist M. Natriuretic role of endogenous oxytocin in male rats infused with hypertonic NaCl. American Journal of Physiology 268, 3: 634-40, 1995.
- 7. Petty M.A, Lang R.E, Unger T, Ganten D. The cardiovascular effects of oxytocin in conscious male rats. European Journal of Pharmacology 112, 2: 203-10, 1985.
- 8. Gimpl G., Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiological Review 81, 2: 629-83, 2001.
- 9. Petersson M., Lundeberg T., Sohlström A., Wiberg U., Uvnas-Moberg K. Oxytocin increases the survival of musculocutaneous flaps. Naunyn-Schmiedeberg's Archives of Pharmacology 81:701-4, 1998.
- 10. Petersson M., Wiberg U., Lundeberg T., Uvnas-Moberg K. Oxytocin decreases carrageenan induced inflammation in rats. Peptides 22, 9: 1479-84, 2001.
- 11. Iseri S. O., Sener G., Saglam B., Gedik N., Ercan F.,. Yegen B. C. Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. Journal of Surgical Research 126, 1: 73–81, 2005.
- 12. Demougeot C., Marie C., Beley A. Importance of iron location in iron-induced hydroxyl radical production by brain slices. Life Science 67, 4: 399-410, 2000.
- 13. Benzie I. F., Strain J. J. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods in Enzymology 299:15-27, 1999.
- 14. Angus D.C., Wax R.S. Epidemiology of sepsis: an update. Critical Care Medicine, 29: 109-16, 2001.
- 15. Guha M., Mackman N. LPS induction of gene expression in human monocytes. Cell Signal, 13,2: 85-94, 2001.
- 16. Gutierrez-Ramos J.C, Bluethmann H. Molecules and mechanisms operating in septic shock: Lessons from knockout mice. Immunology Today 18, 7: 329-34, 1997.
- 17. Gitto E., Karbownik M., Reiter R.J,. Tan D. X, Cuzzocrea S., Chiurazzi P., Cordaro S., Corona G., Trimarchi G., Barberi I. Effects of melatonin treatment in septic newborns. Pediatric Research 50, 6: 756-60, 2001.
- 18. Spangelo B.L., De Holl P.D, Kalabay L., Bond B.R., Arnaud P. Neurointermediate pituitary lobe cells synthesize and release IL-6 in vitro: effects of lipopolysaccharide and IL-1 beta. Endocrinology, 135, 2: 556-63, 1994.
- 19. Williams K.I., El Tahir K.E. Effects of uterine stimulant drugs on prostacyclin production by the pregnant rat myometrium. I. Oxytocin, bradykinin and PGF2 alpha. Prostaglandins 19, 1: 31-8, 1980.
- 20. Pavlova E.L., Lilova M.I., Savou V. M. Oxidative stres in children with kidney disease. Pediatric Nephrology 19: 1599-1604, 2005.
- 21. Fridovich I. Forefronts in nephrology: summary of the newer aspects of renal cell injury. Kidney International 42, 3: 523-39, 1992.
- 22. Biyikli N.K., Tuğtepe H., Sener G., Velioğlu-Ogunç A., Cetinel S., Midillioğlu S., Gedik N., Yeğen B.C. Oxytocin alleviates oxidative renal injury in pyelonephritic rats via a neutrophil-dependent mechanism. Peptides 27, 9: 2249-57, 2006.
- 23. Tuğtepe H., Sener G., Biyikli N.K., Yüksel M., Cetinel S., Gedik N., Yeğen B.C. The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regulatory Peptites 2007;140 (3):101–108, 2007.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 17 Nisan 2018 |
| Gönderilme Tarihi | 11 Nisan 2017 |
| Yayımlandığı Sayı | Yıl 2018 Cilt: 9 Sayı: 1 |
SDÜ Sağlık Bilimleri Dergisi, makalenin gönderilmesi ve yayınlanması dahil olmak üzere hiçbir aşamada herhangi bir ücret talep etmemektedir. Dergimiz, bilimsel araştırmaları okuyucuya ücretsiz sunmanın bilginin küresel paylaşımını artıracağı ilkesini benimseyerek, içeriğine anında açık erişim sağlamaktadır.