Journals / Genel Tıp Dergisi / 2003 / Cilt: 13 - Sayı: 3

The effects of İNOS inhibitors and antioxidants on kidney pathology and function in sepsis

Sepsiste indüklenebilen nitrik oksit sentaz inhibitörü (iNOS) ve antioksidanların böbrek hasarı ve fonksiyonlarına etkileri

Pages
95–103
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Conclusion: Aminoguanidin and pentoxifillin may be added to treatment protocols in sepsis in order to prevent kidney tissue damage and dysfunction both of which (at least partially) caused by elevated NO levels.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: The aim of this study is to investigate the effects of pentoxyfillin, L-arginin and aminoguanidin on plasma malondialdehyde (MDA) and nitric oxide (NO) levels, and to determine the relations between MDA and NO levels on kidney pathology and functions.
📊
Key Findings & Data:The rats were divided into 6 groups, each containing 10 subjects.
💡
Conclusion & Impact:Conclusion: Aminoguanidin and pentoxifillin may be added to treatment protocols in sepsis in order to prevent kidney tissue damage and dysfunction both of which (at least partially) caused by elevated NO levels.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Modeller · teorik · Pentoksifilin

Abstract

Objective: The aim of this study is to investigate the effects of pentoxyfillin, L-arginin and aminoguanidin on plasma malondialdehyde (MDA) and nitric oxide (NO) levels, and to determine the relations between MDA and NO levels on kidney pathology and functions. Methods: Sixty Wistar Albino rats were used. The rats were divided into 6 groups, each containing 10 subjects. Sepsis was induced by cecal ligation and puncture (CLP) method. Group I: Sham group, Group II: CLP (sepsis), Group III: CLP + 10 mg/kg L-arginin administration, Group IV: CLP + 15 mg/kg aminoguanidin administration, Group V: CLP + L-arginin + aminoguanidin (as groups III and IV) Group VI: CLP+15 mg/kg/day pentoxyfillin. Blood samples were taken for the determination of NO, MDA, leukocyte counts, BUN, creatinine and as well as 1 g kidney tissue sample was obtained for determination of tissue damage. Results: Leukocyte count increased in CLP induced groups significantly. While NO levels were significantly higher in sepsis and L-arginin groups, the levels in aminoguanidin and aminoguanidin + L-arginin groups were similar to Sham group. BUN, creatinine levels were significantly higher in CLP applied groups thari in sham group, while values in aminoguanidin and aminoguanidin + L-arginin showed a significant improvement compared to sepsis and L-arginin groups. Renal tissue damage in sepsis and L-arginin groups were more severe than the other groups. MDA levels in CLP induced groups were found to be higher than the sham group. Conclusion: Aminoguanidin and pentoxifillin may be added to treatment protocols in sepsis in order to prevent kidney tissue damage and dysfunction both of which (at least partially) caused by elevated NO levels.

Özet

Amaç: Çalışmanın amacı deneysel sepsis modelinde pentoksifilin, L-arginin ve aminoguanidinin plazma nitrik oksid (NO) ve malondialdehit (MDA) düzeylerine etkisini belirlemek, NO 've MDA düzeyleri ile böbrek hasarı ve böbrek fonksiyonları arasındaki ilişkiyi incelemektir. Yöntem: Wistär albino cinsi 60 rat kullanıldı. Hatlar 10'arlı 6 gruba ayrıldı. Ratlarda çekum ligasyon-perforasyon (CLP) yöntemi ile sepsis geliştirildi. Ratlar, Grup I: Sham işlemi, Grup II: CLP (sepsis), Grup III: CLP + 10 mg/kg L-arginin , Grup IV: CLP +15 mg/kg aminoguanidin, Grup V: CLP + L-arginin + aminoguanidin (aynı dozlar), Grup Vl: CLP +15 mg/kg pentoksifilin şeklinde gruplara ayrıldı, işlemden 24 saat sonra ratlardan NO, MDA, lökosit, BUN, kreatinin tayini için kan örnekleri ve doku hasarını belirlemek için 1 g böbrek doku örnekleri alındı. Bulgular: Lökosit sayısı CLP uygulanan gruplarda anlamlı olarak arttı. NO düzeyleri sepsis grubu ve L-arginin grubunda anlamlı olarak yükselirken, aminoguanidin ve aminoguanidin + L-arginin gruplarında sham grubuna benzer bulundu. CLP uygulanan gruplarda BUN, kreatinin, sham grubuna göre anlamlı olarak yüksekti, ancak pentoksifilin, aminoguanidin ve aminoguanidin + L-arginin gruplarının değerleri sepsis ve L-arginin gruplarına göre anlamlı olarak düzelme gösterdiler. Sepsis ve L-arginin gruplarındaki MDA düzeyleri sham grubuna göre anlamlı olarak yüksek bulundu. Sonuç: Sepsiste artan MDA ve NO'nun neden olduğu böbrek hasarını ve böbrek fonksiyonlarmdaki bozulmayı önlemek amacıyla tedavi protokollerine pentoksifilin ve aminoguanidin eklenebilir.

🔖

Cite This Article

GÖLCÜK, M., TOPRAK, Ş., ŞAHİN, M., PAŞAOĞLU, H. (2003). The effects of İNOS inhibitors and antioxidants on kidney pathology and function in sepsis. Genel Tıp Dergisi, Cilt: 13 - Sayı: 3, 95–103. https://ajindex.com/articles/224984

References (19)

  1. Abraham E. Rapidly expanding horizons. New Horizons 1993;1:1-2
  2. Bone RC. Sepsis and septic shock. Consultant series in infectious disease. Ann Inter Med 1993;3:5-25
  3. Young LS. Sepsis syndrome. In: Mandell GL, Bennett JE, Dalin R, editors. Principles and practice of infectious disease 4th ed. New York: Churchill Livingstone; 1995. p.690-705
  4. Lehr HA, Bittinger F, Kirkpatrick CJ. Microcirculatory dysfunction in sepsis: A pathogenetic basis for therapy. J Pathol 2000;190:373-86
  5. Elsasser S, Schachinger H, Strabel W. Adjunctive Drug treatment in severe hypoxic respiratory failure. Drugs 1999;58:429-46
  6. Wanecek M, Weitzbeg E, Runedil A, Oldner A. The endotelian system in septic and endotoxin shock. Eur J Pharmacol 2000;407:1-7
  7. Mehta S, Javeshghani D, Datta P, Levy RD, Magder S. Porcine. Endotoxemic shock is associated with increased expired nitric oxide. Crit Care Med 1999;27:385-93
  8. Volk T, Kox WJ. Endothelium function in sepsis. Infan Res 2000;49:185-98
  9. Karima R, Matsumoto S, Higashi H, Matsushima K. The molecular pathogenesis of endotoxic shock and organ failure. Molecular Med Today 1999;123-32
  10. Hussein Z, Beerahee M, Grover R, Jordan B, Jeffs R, Donaldson J, et al. Pharmacokinetics of nitric oxide syntase inhibitor L-N-metyargininehydrochloride in patients with septic shock. Clin Pharmacol Ther 1999;65:1-9
  11. Prins HA, Houdijk AP, Wiezer MJ, Teerlink T, van Lambalgen AA, Thijs LG. The effect of mild endotoxemia during low arginine plasma levels on organ blood flow in rats. New Horizons 2000;5:66-8
  12. Shhoonover LL, Stewart AS, Clifton GD. Hemodynamic and cardiovascular effects of Nitric Oxide modulation in the therapy of septic shock Pharmacotherapy 2000;20:1184-97
  13. İskit AB, Sungur A, Gedikoğlu G. The effects of basentan, aminoguanidine and L-cavanine on mesenterric blood flow, spleen and liver in endotoxaemic mice. Eur J Pharmacol 1999;379:73-80
  14. Gibaldi M: What is NO and why are so many people studying it? J Clin Pharmacol 1993;33:488-96
  15. Archer S: Measurement of nitric oxide in biological molecules. FASEB J 1993,7:349-60
  16. Knowles R: Nitric oxide syntheses. Biochem 1993. p:3-6, 17. Grisham MB: Reactive metabolites of oxygen and nitrogen biology and medicine. 1992. p 76-84
  17. Wennmalm A, Edlund A. Metabolism and excretion of nitric oxide in humans. Circ Res 1993;73:1121-7
  18. Lazaron V. NO barrier too tight. Crit Care Med 1999;27:2318-9
  19. Kan H. Is big NO little evil twin? Crit Care Med 2000;28:16