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Tavşanlarda oluşturulan deneysel sepsis modelinde düşük doz n-asetilsistein tedavisinin etkinliği

Efficacy oflow dose n-acetylcystein theraphy on experimental rabbit sepsis model

Journal Name:

  • Selçuk Tıp Dergisi

Publication Year:

  • 2004

Key Words:

Keywords (Original Language):

Author NameUniversity of Author
Abstract (2. Language): 
Purpose: To determine the effect of NAC therapy on plasma levels. the protectıve role of tissue ınjury and organ dys-functıon of free oxygen radicals in experimental sepsis model. Material and method: 30 female rabbits were divided into 3 groups. each composed of 10 rabbits. Sepsis was constituted by caeucum lıgation perforation tecniçue. Groups named sham, sepsis and sepsis + NAC (lOmg/kg/dayj were formed and medication was given I2and 24 hours after caeucum lıgation and perforation. At the same time blood samples to measure blood gases, plasma glutathıonfGSH}. malondialdehyde/MDA} and biochemical diagnosis were collected. Tissue samples were obtained. Findings: Plasma GSH levels were elevated in NAC group with respect to sepsis group/P<0.05}. Plasma MDA levels were decreased in sepsis group when compared to NAC group(P<0.05}. Liver tissue MDA levels were found to be same ın both groups. AST, ALT and creatınine values vvere elevated signifıcantly ın NAC group when compared to sepsis groupfP<0.05}. Apoptosis in lıver tissue was signifıcantly decreased ın NAC group when compared to sepsis group(P<0.05}. Degree of mononuclear infıltration İn kidneys were decreased in NAC group when compared to sepsis group(P<0.05). Conclusion: Application oflovv dose NAC. an antıoxidative agent, in experimental sepsis model has beneficıal effects on pulmonary functions and plasma MDA GSH levels. More and comprehensive studies vvhich tests different NAC doses are needed to determine the role for NAC in experimental sepsis model.
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Abstract (Original Language): 
Anaç: Deneysel sepsis modelinde N-asetılsisteın'ın (NAC) serbest oksijen radikalleri ve plazma düzeylerine olan etki¬lerini, organ fonksiyon bozuklukları ve doku hasarını önlemedeki rolünü belirlemektir. Materyal ve metod: 30 dişi tavşan 1CVarlı gruplara ayrıldılar. Tavşanlarda çekum ligasyon perforasyon (ÇLPj yöntemiyle sepsis oluşturuldu. Sham grubu, sepsis grubu ve sepsis + NACflO mg/kg/günj şeklinde gruplar oluşturulup, ilaçları CLP den hemen sonra, I2.ve24. saatte verildi. Aynı saatlerde kan gazları, plazma glutatyonfGSH}, malondialdehidfMDA}, biyokimyasal tetkik için kan örnekleri alindi- Doku örnekleri alındı. Bulgular: Sepsis grubuyla kıyaslandığında NAC grubunda plazma OSH artmış (P<0.05} ve MDA değerleri azalmış bulundu (P<0.05 }. NAC grubunda SGOT. SGPT ve kreatinin değerlen sep¬sis grubuna göre artmış bulundu (P<0.05}. NAC grubunun arteriyel kan P02 ve Sa02 değerleri sepsis grubuna göre artmış bulundu (P<0.05}. NAC grubunda karaciğerin histopatolojik incelemesinde apopitoz derecesi incelemesinde sepsis grubuna göre anlamlı düzeyde azalmıştı (P<0.05}. NAC grubunun böbrekteki mononükleer hücre ınfiltrasyonu derecesi sepsis grubuna göre anlamlı düzeyde azalmış olarak bulundu (P<0.05}. Sonuç: Deneysel sepsis modelinde antioksidan bir ajan olan NAC'in düşük doz uygulanmasında plazma MDA GSH düzeylerine ve akciğer fonksiyonlarına olumlu etkileri mevcuttur. Daha kapsamlı ve yeni çalışmalarla NAC'in değişik dozlarda verilmesiyle sepsis tedavisinde NAC tedavisinin önemi daha iyi anlaşılacaktır.
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  • Turkish

REFERENCES

References: 

vincent JL Update on sepsis: Pathophysiology and treat-
rnent Açta Clinica Belgica 2000; 55: 79-87.
2. Buckman TD. (diriğ AS, Eiduson S, Sutphin MS, SteinbergA. Glutathion peroxidase and CT scan abnor-malities in sehizophrenia, Biol Psychiatry 1987; 28:1349¬56.
3. Cadet JL Free radıcal mechanisms in the central nervous system: an overview, IntJ Neurosci 1988; 40:13-8
4. Hallivvel B. Lipid peroxidatıon, oxygen radicals, celi dam-age, and antioxidant therapy. The Lancet 1984; 23:1396-8.
5. McCreadie RG, MacDonaid E. VViles D. Campbell G, Paterson JR. The Nithsdale sehizophrenia survey XIV.PIasma lipid peroxide and serum vitamin E level in patient with and without tardive diskinesia and in normal subject, Br J Psychiatry 1995; 167:610-7.
6. Reddy R, Sahebarao M. Mukherjee S, Enzymes of the antioxıdants defence system in chronıc schizophrenic patients. Biol Psychiatry 1991; 30:409-12.
7. Southorn PA Garth P. Free radicals in the medicine. II.
ınvolvement in human disease. Mayo Clin Proc 1998; 63:390-408.
8. Cotgreave !A N-Acetylcysteine: pharrnacological consider-
ations and experimental and clinical applications, Adv. Phamrıacol. 1997. 38: 205-27.

9. Oka S, Kamata H, Kamata k. Yagisawa H, Hirata H, N-Acetylcysteine suppresses TNF-ınduced NF-KB activation through inhibition of InB kınases, FEBS Lett 2000; 472: 196-202.
10. Kim H. Seo J. Roh KH, Um JW. Kim KH, Suppression of NFKB activation and eytokine produetion by N-aceiylcys-teine in panereatic acinar cells, Free Radic. Biol. Med. 2000; 29: 674- 83.
11. Demols A Van Laethem JL, Ouertinmont E, Legros F, Louis H, Le Moine O. N-Acetylcysteine decreases severity of acute panereatitis in mice, Pancreas 2000; 20: 161-9.
12. İlker D, Murat K, Burak M.Y.C, Serap B, Seranay E, Serdar H. O. The effects of cycioîponne on antîoxidant enzyme aetivites and malondialdehyde levels in rabbit hepatic tis-sues. Transplant Immunology 2002; 10: 255-8.
13. Van Sureli C, Boczkovvski J, Pasguier C, Du Y, Franzini E, Aubier M. Effects of N-acetylcysteine on diaphragmaoc funetion and malondialdehyde content in Escherichia coli endotoxemic rats. Am Rev Respir Dis. 1992; 146. 730-4.
14. Konrad F. Sthoenberg MH. Wiedmann H, Kilian J, Georgieff M. The application of n-acelyleysteine as an antioxidant and mucofytic in mechanical ventilation in intensive care patients. A prospeetive, randomized, placebo-controlled. double-blind study Anaesthesist. 1995; 44: 651 -8

15 Hallıwel 6 Reactıve oxygen specıes ın Irvıng systems; cru-osıty. cause. or consequence Lancet 1994; 344:721-4
16 Ozdulger A Önel I, Köksel O, Önel L et ali. The protectıve effect of N-acetylcysteıne on apoptotıc lung mjury ın cecal lıgatıon and puncture-ınduced sepsis model. Shock. 2003; !9(4J:366-72
17. Rank N. Michel C. Haertel C Lenhart A et ali; N-acetyl-cysteine ıncreases liver blood flovv and ımproves liver function ın septıc shock patıents: results of a prospectıve. randomızed. double-blmd study Cnt Care Med 2000; 28[ 12] 3799-807
18 Ozaras R. Tahan V. Aydın S. Uzun H. Kaya S. Senturk H N- acetylcysteıne attenuates alcohol-ınduced oxıdatıve stree ın rats WorId J Gastroenterol 2003; 9:791-4.
19. Anton EO. Ouinella AG. Sato AL Lıova J. Perez LF. Cecal lıgatıon and puncture as a model of sepsis m the rai: ınfluence of the puncture size on mortalıty, bacteremıa. endotoxemıa and tumor necrosıs factor alpha levels Eur Surg Res 2001. 33: 77-9.
20. Draper HH, Hadley M Malondialdehyde determmatıon as index of fıpıd peroxıdatıon. Methods Enzymol. 1990; 186: 421-431.
2! Powell RJ. Machıedo GW. Rush BF Jr, Dıkdan GS. Effect of oxygen-free radical scavengers on survıval ın sepsis. Am Surg 1999; 57; 86-8.
22 Goode HF. Webster NR. Free radicals and antıoxıdants ın sepsis clinıcal oxidant research Group Cnt Care Med 1993; 21: 1770-6
23. Henderson A Hayes P. Acetylcysteıne as a cytoproteaıve antıoxıdant in patıents vvith severe sepsis: potential new use for an old drug. Australıa Ann Pharmacother 1994; 28; 1086-8
24. Gryasettin B. Okkes Y, Sait C. Abdullah Y, Ferit M. G. Effects of certaın micronutrients and melatonin on plas-ma lıpıd, lipid peroxidation and homocysteme levels ın rats. Archives of Medıcal Research 2002; 33: 515-9.
25. Bhattacharyya J, Data AG. Studıes on the effects of lıpopolysacchande on lipid peroxıdation of erythrocyte and ıts reversal by mannıtol and glycerol. Journal of Physıology and pharmacology 200; 52:145-52.
26 Ozaras R. Tahan V. Aydın S. Uzun H. Kaya S. Senturk H N-acetylcysteine attenuates alcohol-induced oxıdative stress in rats World J Gastroenterol 2003; 9: 791-4.
27. Van Sureli C. Boczkovvskı J. Pasquıer C, Du Y, Franzıni E. Aubıer M Effects of N-acetylcysteine on dıaphragmatıc function and malondialdehyde content ın Escherıchıa colı endotoxemıc rats. Am Rev Respır Dıs. 1992. 146:730¬734.
28. Katsuya M. Kahoru N. Shun-ıchi K. Hıdefumı O. Propofol attenuates diaphragmatic dysfunction ınduced by septıc peritonitıs ın hamsters Anesthesıology 200 i. 94. 652-60.
29. Govinder JS. Flora K, Prahlad KS Beneficıal effects of s-adenosyl-l-methıonine on amınolevulımc acıd dehy-dratase. glutathıone and lıpıd peroxidatıon dunng acute lead- ethanol admimstration in mice Alcohol 1999; 18: 103-8.
30 Chrıstian L ü U. Glutathone and glutathione ethyl ester supplemantatıon of mıce after glutathione homeostasıs dunng exercıse. Am Socıety for Nutritional Sciences 1998; 2420-6.
31 Zhang H. Spapen H. Nguyen DN. Benlabed M. Buurman WA Vıncent JL Protectıve effects of N-acetyFL-cysteme ın endotoxemıa Amj Physıol 1994; 266 1746-54
32 Sanz AG. Obeso A Agapıto MT. Gonzalez C Reduced to oxıdızed glutathione ratios and oxygen sensıng ın calf and rabbıt carotıd body chemoreceptor cells Journal of Physıology 2000; 537: 209-20
33 Zhang H. Spapen H, Nguyen DN. Benlabed M. Buurman WA Vıncent JL Protectıve effects of N-acetyH.-cysteıne m endotoxemıa AmJ Physiol 1994. 266: 1746-54.
34 Perıstens P. Clark BD. Gatti S. Faggıonı R. Mantovanı A_ Mengozzı M. Orencole SF. Sıron/ M. Ghezzı P. N-acetyl¬cysteıne and glutathione as ınhıbıtors of tumor necrosıs factor productıon. Celi Immunol. 1992; 140:390-9

35. Powell RJ. Machiedo GW. Rush BF Jr. Dıkdan GS Effect of oxygen-free radical scavengers on survrval ın sepsis Am Surg. 1991; 57; 86-8
36. Goode HF. VVebster NR Free radicals and antıoxıdants ın sepsis Cnt Care Med 1993; 21:1770-6.
37. Victor VM, Guayerbas N. Garrote D. Del Rio M. De la Fuente M Modulatıon of murıne macrophage function by N-acetylcysteıne ın a model of endotoxıc shock Bıofactors 1999. 10:347-57
38. Broner CW, Shenep JL. Stidham GL Stokes DC. Faırlough D. Rehg JE. Hıldner WK Effect of antioxıdants ın exper/-mental Escherichıa coli septıcemia. Orc Shock 1989; 29: 77-92
39. De la Fuente M, Victor VM. Ascorbıc acid and N-acetyl¬cysteine improve ın vitro the function of lymphocytes from mice with endotoxin-induced oxidatıve stress Free Radic Res. 2001; 35: 73-84.
40. Ozdulger A Cınel 1, Köksel O. Cinel L et al, The protectıve effect of N-acetylcysteıne on apoptotıc lung mjury ın cecal lıgatıon and puncture-ınduced sepsis model Shock 2003,19: 366-72.
41. Heller AR. Groth G, Heller SC, Breitkreutz R. Nebe T. Ouintel M. Koch T. N-acetylcysteine reduces resp/ratory burst but augments neutrophil phagocytosıs m ıntensrve care unıt patıents. Cnt Care Med. 2001; 29:272-6.
42. Spapen H. Zhang H. Demanet C. Vlemınckx W. Vıncent JL Huyghens L Does N-acetyl-L-cysteme ınfluence cytokıne response during early human septıc shock? Chest. 1998; 1 13: 1616-24.
43. Dombusch HJ, Strenger V, Kerbl R, Lackner H. Schvvınger W, Sovınz P. Urban C. Procalcıtonın and C-reactıve pro¬tein do not dıscrımınate betvveen febnle reactıon to antı-T-Iymphocyte antıbodıes and Gram-negatıve sepsis Bone MarrovvTranspfant. 2003; 32: 941-45.
44 Kepa L Oczko-Gr2esık B Usefulness of plasma C-react/ve protein |CRP) estımation ın patıents wıth Dacterıal sepsis Przegl Epıdemıol 2001; 55: 63-7
45. Molnar Z. Szakmany T, Koszegı T Prophylactıc N-aceryl-cysteine decreases serum CRP but not PCT levels and mıcroalbumınurıa follovvıng majör abdomınal surgery A prospectıve. randomısed, double-blınded. placebo-con-trolled clinıcal trial. Intensıve Care Med 2003; 29. 749¬55.
46 Ruetten H. Thıemermann C. Effect of caipam ınhıbıtor I, an ınhıbıtor of the proteolysıs of I kappa B, on the cırcu-latoıy failure and multiple organ dysfunction caused by endotoxrn ın the rat Br J Pharmacol. 1997; 121: 695¬704

47. Ravvson JS, Achord JL Shock liver. South Med J 1985; 78: İ42İ-5.
48. U/ang P, Ba 7F, Tair S M, 7hou M. Chauriry (H Alterations ın cırculating blood voiume during polymicrobial sepsis. Circ Shock 1993; 40: 92-98.
49. Hong KW, Kim KE, Rhim BY. Lee WS, Kim CD. Effect of rebamipide on liver damage and increased tumor necro-sıs factor in a rat model of endotoxin shock. Dig Dis Sci. 1998; 43:154-9
50. Hıdeki Y, Tomohiro W. Hatsue M. Kazuo E, Tsunemichi H. akio K, Ravi G, Shoichi F. İn vivo evidence for accelerared generation of hydroxyl radicals in liver of long-evans cin-namon |LEC] rars with acute hepatitis. Free Radical Biologyand Med. 2001; 30: 547-54.
5İ Al; O, İsmail C, Oğuz K, Leyla C. Dincer A Ali U, Hülya O, Murat D, Uğur O. The protectıve effects of N-acetylcys-teine on apopitotic lung injury in cecal ligation and punc-ture-induted sepsis model. Shock 2003. 19: 366-72
52. Corinne RS, Miranda A, Vvinkelhuyzenjanssen L, Colinda JMA, Johannes FLM van O, Tjomme Van Der B. Low-dose n-acetylcysteine protects rats against endotoxin-medıated oxidative stress, but high-dose "ıncreases mor-tality. AmJ Respir Crit Care Med. 1998, 157.1283-93.

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