Perbedaan ekspresi TGF-B1 dan Fibrosis Interstisial pada kejadian Nefrotoksis Doxorubicin dan Nefroprotektif Pentoxifylin
https://doi.org/10.33476/jky.v17i2.208
Keywords:
doxorubicin, pentoxyfilline, interstitial fibrosis, albuminuriaAbstract
Nephrotoxic effects of Doxorubicin (DXR) is still a problem in clinical practice. On the other hand Pentoxyfilline (PTX) as an electron-donor material can be nephroprotective. Therefore, combination of DXR and PTX would be expected to reduce nephrotoxic effects of DXR. In this study we examined the effects of PTX on TGF-B1 expression and interstitial fibrosis in an experimental model of DXR nephropathy in mice. Mice were divided into three groups of eight each i.e. untreated Swiss mice (controls), DXR treatment alone to induce nephropathy, and DXR treatment followed by PTX. Following 4 week treatment, each group was sacrificed. Examination of TGF-B1 expression was carried out by immunohistochemistry employing monoclonal antibody. Interstitial fibrosis examination was performed by a histopathologist using Verheoff van Giesen staining and the one way Anova was used for statistical analysis. It was observed that DXR treatment followed by PTX treatment prevented the increase of TGF-B1 expression and interstitial fibrosis in mice with DXRnephropathy (p<0.05). These findings suggested the beneficial nephroprotective effect of PTX.References
Baratawidjaja KG, Iris R2009. Imunologi Dasar. Edisi VIII. FK Universitas Indonesia.
Bawazier LA2006. Albuminuri. Buku Ajar Penyakit Dalam: Ed IV. Dept. Penyakit Dalam. Fakultas Kedokteran Universitas Indonesia.
Belloc F, Dumani P 1995. Effect of Pentoxifilline on Apoptosis of Cultural Cells.J.Cardiovase Pharmacal 25:71–74.
Blobe GC, Schiemann WP, and Lodish HF. 2000.Role of Transforming Growth Factor ß in Human Disease.N Engl J Med 343(3):1350-58.
David D, Abbe S 1993. Protective Effect of Recombinant Human Interlukin-1? in Doxorubicin Treated Normal and Tumor Bearing Mice. Cancer Research S3:1565 – 1570.
Davila ME, Esqueda, Martinez F, Morales 2004. Pentoxifyllin Diminshes the Oxidative Damage to Renal Tissue Induced Shreptotozocin in Rat. Experimental Diab Res 5: 245–251.
Erlan JF, Desmant 2001.Transfers of Ferritin-Bound Iron to Andriamicyn.FEBS letters 176: 97 – 100.
Fang CC, Lai MN, Chien CT, Hung KY, Tsai CC, Tsai TJ, and Hsieh BS 2003. Effects Of Pentoxifylline On Peritoneal Fibroblasts And Silica-Induced Peritoneal Fibrosis.Peritoneal Dialysis International 23: 228–236.
Gameson R, Reeves WB 2007. TNF-? Mediates Chemokine and Sitokine Expression and Renal Injury in Cesplation Nephrotoxcity. J. Clin Invest 110: 835-842.
Guntur AH 2006. SIRS dan SEPSIS (Imunologi, Diagnosis, Penatalaksanaan). Sebelas Maret University Press. Surakarta.
Guo J, Ananthakrishnan R, Qu W, Lu Y, Reiniger N, Zeng S, Ma W, Rosario R, Yan SF, Ramasamy R, D’Agati V,and Schmidt AM 2008. RAGE Mediates Podocyte Injury in Adriamycin-induced Glomerulosclerosis. J Am Soc Nephrol19: 961–972.
Hasinoff BB 1989. Self Reduction of the Iron (III) Doxorubicin Complex.Free Radic Bio Med 7(6): 583 – 93.
Koli K, Saharinen J, Hyytiainen M, Penttinen C, Keski-Oja J 2001.Latency, activation, and binding proteins of TGF-beta.Microsc Res Tech52:354–362.
Kupsakova, Docolomansky P, Ryber M, Brier A 2002. Carbonyl Group of Aliphatic Side Chain on Pentoxifyllin does not Play Role for P. Glycoprotein Antagonizing Effect of Pentoxifyllin. Gen Physol Biophys 21: 471–8.
Li J, Campanale NV, Liang RJ, Deane JA, Bertram JF, and Ricardo SD 2006. Inhibition of p38 MitogenActivated Protein Kinase and Transforming Growth Factor-B1/Smad Signaling Pathways Modulates the Development of Fibrosis in Adriamycin-Induced Nephropathy. Am J Pathol 169(5): 1527–1540
Lin SL, Chen YM, Chien CT, Chiang WC, Tsai CC, Tsai TJ 2002. Pentoxifylline Attenuated the Renal Disease Progression in Rats with Remnant Kidney. J Am Soc Nephrol 13: 2916–2929
Loscalzo J 2009. Azotemia and Urinary Abnormalitis. In Harison’s Manual of Medicine. 17th edition. New York, Mc Graw Hill, pp 274-280
Mandy Y, Magy Z 1997. Effect of Tumor Necrosis Factor for Pentoxifilline on Icam-1 Expression on Human Poly Morpho Nuclear Granulocytes.Int Arch Allergy Immunal 114:329 – 335.
Mayes PA 2003.Structure and Function of Lipofilic Vitamin.Harpers Biochemistry.25th edition. 613–622.
Robbins and Cotran 2005.General Pathology.Bassic Pathology Dissease. EGC;I:20-43.
Sankar 2006.Handbook of Transcription Factor NF Kappa B Bocca Rator.CRC ISBN 8493 - 2794 – 6.
Strutz F, Heeg M, Kochsiek T, Siemers G, Zeisberg M, Muller GA 2000. Effects of pentoxifylline, pentifylline and gamma-interferon on proliferation, differentiation, and matrix synthesis of human renal fibroblasts.Nephrol Dial Transplant 15:1535–1546.
Suryohudoyo P 2000.Oksidan, anti-oksidan dan Radikal Bebas.Kapita Selekta. Ilmu Kedokteran Molekuler. CV Agung Seto. Jakarta. Hal 31 – 47.
Tamaki K, Seiya O, Takashi A 1994. TGF-B in Glomerulosklerosis and Interstitial Fibrosis, of Andriamicyn Neprhopaty.Kidney International
:525 – 536.
Usta Y, Ismailaglu 2004. Effect of Pentoxifilline Adriamicun (DXR) Included Renal Dissease in Rats. Pedriatri Nephoral19: 840–843.
Wang W, Koka V, Lan HY 2005. Transforming growth factor-beta and Smad signalling in kidney diseases.Nephrology (Carlton) 10:48–56.
Wang Y, Wang YP 2001. Role of CD 8th Cells in the Progression of Murine Adiramycin Neprhropaty. Kidney International 59:941 – 949.
Weir MR 2007.Microalbuminuria and Cardiovascular Disease.Clin J Am Nephrol 2: 581-590.
WHO 2008.WHO Global Info Base. http://www.who.int/infobase-/cancer.aspx (diunduh tanggal 12 Pebruari 2010)
WHO 2010.Cancer.http://www.who.int/cancer (diunduh tanggal 12 Pebruari 2010)
Xiong LJ, Zhu JF, Luo DD, Zen LL, Cai SQ 2003. Effects of pentoxifylline on the hepatic content of TGF-b1 and collagen in Schistosomiasis japonica mice with liver fibrosis.World J Gastroenterol 9(1):152-154