Ratlarda Pentoksifilinin Kontrast Nefropatisi Üzerine Koruyucu Etkileri

Öz

Amaç: Antioksidan ve immüno-modülatör etkileri olan pentoksifilinin PTX , renal iskemi-reperfüzyon hasarını azalttığı gösterilmiştir. PTX’in kontrast kaynaklı nefropatinin CIN gelişmesine karşı koruyucu bir rolü olup olmadığını araştırdık.Gereç ve Yöntemler: Toplam 24 tane wistar-albino dişi sıçan rastgele-altışarlı kontrol C , kontrast madde CM , PTX ve PTX + CM şeklinde dört gruba ayrıldı. Kontrol ve CM grupları haricindekilere 5 gün boyunca günde bir kez PTX verildi. CIN, 48 saat dehidrasyondan sonra intravenöz yüksek ozmolar kontrast madde olan -diatrizoatla 6 mL/kg indüklendi. Bazal ve post-CIN böbrek fonksiyon parametreleri, inflamatuar parametreler, serum ve renal doku oksidatif stres belirteçleri ileri oksidasyon protein ürünü ve malondialdehid serum seviyeleri ve histopatolojik lezyonlar değerlendirildi.Bulgular: Serum kreatinin ve kan üre nitrojen düzeylerindeki artış ve kreatin klerensinde azalma sadece CM grubunda anlamlıydı P

Anahtar Kelimeler

• Kontrast nefropatisi, Pentoksifilin, Böbrek, Önleyici, Oksidatif stres

The Protective Effects of Pentoxifylline on Contrast Induced Nephropathy in Rats

Abstract

Objective: Pentoxifylline PTX , which has antioxidant and immunomodulatory effects, has been shown to attenuate renal ischemia-reperfusion injury. We aimed to investigate whether PTX might have a preventive role against the development of contrast induced nephropathy CIN .Material and Methods: A total of 24 Wistar-albino female rats were randomly divided into four groups n=6 each as follows; control C , contrast material CM , PTX, and PTX+CM. Except the control and CM groups, the groups were given PTX once daily orally for 5 days. CIN was induced by administration of intravenous high-osmole contrast material-diatrizoate 6 mL/kg after 48 hour of dehydration. Basal and post-CIN kidney function parameters, inflammatory parameters, serum and renal tissue oxidative stress markers serum levels of advanced oxidation protein product and malondialdehyde , and histopathological lesions were assessed.Results: The increase in serum creatinine and blood urea nitrogen levels was significantly higher only in the CM group P

Keywords

• Contrast nephropathy, Pentoxifylline, Kidney, Preventive, Oxidative stress

References

1. Roozbeh J, Jahromi AH, Sharifian M, Pakfetrat M, Afshariani R. Protective effect of pentoxifylline on contrast induced nephropathy. Saudi J Kidney Dis Transpl 2008;19:985-6.
2. Thomsen HS, Stacul F, Webb JAW. Contrast medium- induced nephropathy. Berlin, Heidelberg, Springer, Contrast Media, 2014:81-104.
3. Koc E, Reis KA, Ebinc FA, Pasaoglu H, Demirtas C, Omeroglu S, Derici UB, Guz G, Erten Y, Bali M, Arinsoy T, Sindel S. Protective effect of beta-glucan on contrast induced-nephropathy and a comparison of beta-glucan with nebivolol and N-acetylcysteine in rats. Clin Exp Nephrol 2011;15:658-65.
4. Jo SH, Koo BK, Park JS, Kang HJ, Cho YS, Kim YJ, Youn TJ, Chung WY, Chae IH, Choi DJ, Sohn DW. Prevention of radiocontrast medium-induced nephropathy using short-term high-dose simvastatin in patients with renal insufficiency undergoing coronary angiography (PROMISS) trial-a randomized controlled study. Am Heart J 2008;155:499 e1-8.
5. Yokomaku Y, Sugimoto T, Kume S, Araki SI, Isshiki K, Chin-Kanasaki M, Sakaguchi M, Nitta N, Haneda M, Koya D, Uzu T. Asialoerythropoietin prevents contrast- induced nephropathy. J Am Soc Nephrol 2008;19:321-8.
6. Buyuklu M, Kandemir FM, Ozkaraca M, Set T, Bakirci EM, Topal E. Protective effect of curcumin against contrast induced nephropathy in rat kidney: What is happening to oxidative stress, inflammation, autophagy and apoptosis. Eur Rev Med Pharmacol Sci 2014;18:461-70.
7. Weisbord SD, Palevsky PM. Prevention of contrast- induced nephropathy with volume expansion. Clin J Am Soc Nephrol 2008;3:273-80.
8. Doherty G, Jensen JC, Alexander H, Buresh C, Norton J. Pentoxifylline suppression of tumor necrosis factor gene transcription. Surgery 1991;110:192-8.

9. Chen YM, Chiang WC, Lin SL, Tsai TJ. Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: An update. J Biomed Sci 2017;24:84.
10. Nasiri-Toosi Z, Dashti-Khavidaki S, Khalili H, Lessan- Pezeshki M. A review of the potential protective effects of pentoxifylline against drug-induced nephrotoxicity. Eur J Clin Pharmacol 2013;69:1057-73.
11. Bhat VB, Madyastha KM. Antioxidant and radical scavenging properties of 8-oxo derivatives of xanthine drugs pentoxifylline and lisofylline. Biochem Biophys Res Commun 2001;288:1212-7.
12. Horvath B, Marton Z, Halmosi R, Alexy T, Szapary L, Vekasi J, Biro Z, Habon T, Kesmarky G, Toth K. In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine. Clin Neuropharmacol 2002;25:37-42.
13. Topsakal C, Erol FS, Ozveren MF, Yilmaz N, Ilhan N. Effects of methylprednisolone and dextromethorphan on lipid peroxidation in an experimental model of spinal cord injury. Neurosurg Rev 2002;25:258-66.
14. Shifow AA, Naidu MU, Kumar KV, Prayag A, Ratnakar KS. Effect of pentoxifylline on cyclosporine-induced nephrotoxicity in rats. Ind J Exp Biol 2000;38:347-52.
15. Yavari V, Ostovan MA, Kojuri J, Afshariani R, Hamidian A, Roozbeh J, Pakfetrat M. The preventive effect of pentoxifylline on contrast-induced nephropathy: A randomized clinical trial. Int Urol Nephrol 2014;46:41-6.
16. Babiak RM, Campello AP, Carnieri EG, Oliveira MB. Methotrexate: pentose cycle and oxidative stress. Cell Biochem Funct 1998;16:283-93.
17. Agmon Y, Peleg H, Greenfeld Z, Rosen S, Brezis M. Nitric oxide and prostanoids protect the renal outer medulla from radiocontrast toxicity in the rat. J Clin Invest 1994;94:1069-75.
18. Carraro M, Mancini W, Artero M, Stacul F, Grotto M, Cova M, Faccini L. Dose effect of nitrendipine on urinary enzymes and microproteins following non-ionic radiocontrast administration. Nephrol Dial Transplant 1996;11:444-8.
19. Rangan GK, Wang Y, Harris DC. Pharmacologic modulators of nitric oxide exacerbate tubulointerstitial inflammation in proteinuric rats. J Am Soc Nephrol 2001;12:1696-705.
20. Navarro-González JF, Mora-Fernández C, de Fuentes MM, Chahin J, Méndez ML, Gallego E, et al. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: The PREDIAN trial. Journal of the American Society of Nephrology 2015;26(1):220-9.
21. Plotnikov MB, Aliev OI, Shamanaev AY, Sidekhmenova AV, Anfinogenova Y, Anishchenko AM, et al. Effects of pentoxifylline on hemodynamic, hemorheological, and microcirculatory parameters in young SHRs during arterial hypertension development. Clinical and Experimental Hypertension 2017;39(6):570-8.
22. Han J, Huez G, Beutler B. Interactive effects of the tumor necrosis factor promoter and 3’-untranslated regions. J Immunol 1991;146:1843-8.
23. Weinberg JB, Mason SN, Wortham TS. Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) messenger RNA (mRNA) expression in HL-60 leukemia cells by pentoxifylline and dexamethasone: dissociation of acivicin-induced TNF- alpha and IL-1 beta mRNA expression from acivicin- induced monocytoid differentiation. Blood 1992;79:3337- 43.
24. Currie MS, Rao KM, Padmanabhan J, Jones A, Crawford J, Cohen HJ. Stimulus-specific effects of pentoxifylline on neutrophil CR3 expression, degranulation, and superoxide production. J Leukoc Biol 1990;47:244-50.
25. Crouch SP, Fletcher J. Effect of ingested pentoxifylline on neutrophil superoxide anion production. Infect Immun 1992;60:4504-9.
26. D’Hellencourt CL, Diaw L, Cornillet P, Guenounou M. Differential regulation of TNF alpha, IL-1 beta, IL- 6, IL-8, TNF beta, and IL-10 by pentoxifylline. Int J Immunopharmacol 1996;18:739-48.
27. Domínguez‐Jiménez C, Sancho D, Nieto M, Montoya MC, Barreiro O, Sánchez‐Madrid F, González‐Amaro R. Effect of pentoxifylline on polarization and migration of human leukocytes. J Leukoc Biol 2002;71:588-96.