Effects of Pentoxifylline on Renal Structure After Urethral Obstruction in Rat: A Stereological Study

Overview

Journal Cent European J Urol

Specialty Urology

Date 2014 Mar 1

PMID 24578857

Citations 6

Authors

Mehdi Shirazi

Ali Noorafshan

Amir Farrokhi

Affiliations

Soon will be listed here.

Abstract

Objective: Chronic renal failure due to tubulointerstitial fibrosis is one of complications of lower urinary tract obstruction. Since pentoxifylline is a xanthine derivative that inhibits some inflammatory mediators, we conducted this study to investigate whether pentoxifylline inhibits renal fibrosis in a rat model of partial urethral obstruction (PUO).

Methods: All the rats underwent experimental PUO. Then, the animals were divided randomly into two groups: positive control group and experimental group. The experimental group received pentoxifylline 100 mg/kg per day via oral gavages for 4-weeks. The control group received the same dose of normal saline. After 4-weeks, all the rats underwent left nephrectomy. Kidney volume and weight and fractional and absolute volumes of the glomeruli, tubules, interstitium and vessels were determined with stereological methods. To reduce the workload of reference (kidney) volume estimation, the total kidney volume was determined after estimation of tissue shrinkage on isotropic uniform random histological sections. The total volume (amount) of each renal structure including fibrosis was estimated to avoid the bias conclusion due to relying on volume density alone.

Results: The absolute volume of interstitial fibrosis was lower in the experimental group (PUO with pentoxifylline treatment) (~84%; p ≤0.006) in comparison with the control group (PUO with no treatment).

Conclusion: Pentoxifylline reduces interstitial renal fibrosis after partial urethral obstruction in rats.

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References

Lin S, Chen R, Chen Y, Chiang W, Lai C, Wu K . Pentoxifylline attenuates tubulointerstitial fibrosis by blocking Smad3/4-activated transcription and profibrogenic effects of connective tissue growth factor. J Am Soc Nephrol. 2005; 16(9):2702-13. DOI: 10.1681/ASN.2005040435. View

Kwon H, Kim S, Chung W, Cho M, Kim J, Moon S . Effect of pentoxifylline on radiation response of non-small cell lung cancer: a phase III randomized multicenter trial. Radiother Oncol. 2000; 56(2):175-9. DOI: 10.1016/s0167-8140(00)00221-8. View

Aslan A, Karaguzel G, Gungor F, Izgut-Uysal N, Aydin F, Melikoglu M . The effects of pentoxifylline on renal function and free radical production in unilateral ureteral obstruction. Urol Res. 2003; 31(5):317-22. DOI: 10.1007/s00240-003-0342-1. View

Nyengaard J . Stereologic methods and their application in kidney research. J Am Soc Nephrol. 1999; 10(5):1100-23. DOI: 10.1681/ASN.V1051100. View

Diamond J, Ricardo S, KLAHR S . Mechanisms of interstitial fibrosis in obstructive nephropathy. Semin Nephrol. 1998; 18(6):594-602. View

Zabel P, Schade F, Schlaak M . Inhibition of endogenous TNF formation by pentoxifylline. Immunobiology. 1993; 187(3-5):447-63. DOI: 10.1016/S0171-2985(11)80356-6. View

Tseng T, Stoller M . Obstructive uropathy. Clin Geriatr Med. 2009; 25(3):437-43. DOI: 10.1016/j.cger.2009.06.003. View

Paramothayan S, Lasserson T . Treatments for pulmonary sarcoidosis. Respir Med. 2007; 102(1):1-9. DOI: 10.1016/j.rmed.2007.08.010. View

Yalniz M, Bahcecioglu I, Kuzu N, Celebi S, Ataseven H, Ustundag B . Amelioration of steatohepatitis with pentoxifylline in a novel nonalcoholic steatohepatitis model induced by high-fat diet. Dig Dis Sci. 2007; 52(9):2380-6. DOI: 10.1007/s10620-006-9194-1. View

10.

Misseri R, Rink R, Meldrum D, Meldrum K . Inflammatory mediators and growth factors in obstructive renal injury. J Surg Res. 2004; 119(2):149-59. DOI: 10.1016/j.jss.2004.02.016. View

11.

Shirazi M, Noorafshan A, Bahri M, Tanideh N . Captopril reduces interstitial renal fibrosis and preserves more normal renal tubules in neonatal dogs with partial urethral obstruction: a preliminary study. Urol Int. 2007; 78(2):173-7. DOI: 10.1159/000098078. View

12.

Reed W, DEGOWIN R . Suppressive effects of pentoxifylline on natural killer cell activity. J Lab Clin Med. 1992; 119(6):763-71. View

13.

Zhang M, Xu Y, Saini H, Turan B, Liu P, Dhalla N . Pentoxifylline attenuates cardiac dysfunction and reduces TNF-alpha level in ischemic-reperfused heart. Am J Physiol Heart Circ Physiol. 2005; 289(2):H832-9. DOI: 10.1152/ajpheart.00178.2005. View

14.

Mandarim-de-Lacerda C . Stereological tools in biomedical research. An Acad Bras Cienc. 2003; 75(4):469-86. DOI: 10.1590/s0001-37652003000400006. View

15.

Coroneos E, ASSOUAD M, Krishnan B, Truong L . Urinary obstruction causes irreversible renal failure by inducing chronic tubulointerstitial nephritis. Clin Nephrol. 1997; 48(2):125-8. View

16.

Payton S . Therapeutic benefit of pentoxifylline for Peyronie's disease. Nat Rev Urol. 2010; 7(5):237. DOI: 10.1038/nrurol.2010.53. View

17.

Shirazi M, Noorafshan A, Kroup M, Tanideh N . Comparison of the effects of captopril, tamoxifen and L-carnitine on renal structure and fibrosis after total unilateral ureteral obstruction in the rat. Scand J Urol Nephrol. 2007; 41(2):91-7. DOI: 10.1080/00365590600917974. View

18.

Fedorowicz Z, Shih-Yen E, Dorri M, Nasser M, Newton T, Shi L . Interventions for the management of oral submucous fibrosis. Cochrane Database Syst Rev. 2008; (4):CD007156. DOI: 10.1002/14651858.CD007156.pub2. View

19.

Hoseini L, Roozbeh J, Sagheb M, Karbalay-Doust S, Noorafshan A . Nandrolone decanoate increases the volume but not the length of the proximal and distal convoluted tubules of the mouse kidney. Micron. 2008; 40(2):226-30. DOI: 10.1016/j.micron.2008.08.004. View

20.

Rule A, Lieber M, Jacobsen S . Is benign prostatic hyperplasia a risk factor for chronic renal failure?. J Urol. 2005; 173(3):691-6. DOI: 10.1097/01.ju.0000153518.11501.d2. View