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Siklosporin A'nın sıçanlarda oluşturduğu nefrotoksisiteye Vitamin C ile Vitamin E'nin ve verapamilin etkilerinin ışık mikroskobunda değerlendirilmesi

Effects of Vitamin C, Vitamin E and verapamil on cyclosporin induced nephrotoxicity in rats: a light microscobic study

Journal Name:

  • Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi

Publication Year:

  • 2005

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Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Aim: Cyclosporin A (CsA) is an important agent used in organ transplantation to prevent rejection. This immunosupressive drug's most important secondary effect is nephrotoxicity. There are two hypotheses for the nephrotoxicity mechanism i) vasoconstruction in afferent arteriole ii) the role of reactive oxygen species. In this study we planned to see the individual or combined effects of antioxidant vitamins E and C with a calcium channel blocker verapamil. Materials and Methods: 25 rats divided into five groups equally; a vehicle group, CsA treated group, CsA + vitamin E and C treated group, CsA + verapamil treated group and CsA+ vitamin E and C + verapamil treated group. CsA administered 50 mg/kg/day (per oral by catheter), vitamin E administered 150 mg/kg/day (intramusculer), vitamin C administered 200 mg/kg/day (intraperitoneal), verapamil administered 0.5 mg/kg/day (intramusculer) for 10 days. At the end of study rats' blood samples and kidney tissues were taken under ether anesthesia. Tissue sections of kidney were fixed in %10 formalin. Parafin sections were cut at 5 |jm, then examined after staining with hematoxylin-eosin. Results: In CsA treated rats, significant morphological changes were observed in kidney sections. Although in CsA + vitamin E,C and CsA + verapamil treated rats, these changes were reduced but the most significant improvement observed in the CsA + vitamin C and E + verapamil treated group. Also most significant rise of antioxidant enzymes, catalaz and glutathion peroxidase in renal tissue was seen in this group. Conclusion: We suggest that using the combination of verapamil, vitamin E and C will be more useful to prevent the nephrotoxicity caused by CsA.
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Abstract (Original Language): 
Amaç: Siklosporin A (CsA) organ nakillerinde atılımı önlemede önemli bir kullanım alanına sahiptir. Bu güçlü bağışıklık sistemini baskılayıcı ajanın en önemli yan etkisi nefrotoksisitedir. Bu yan etkinin oluşumunda suçlanan en önemli iki mekanizma; i) böbrekte afferent arteriyolde yaptığı vazokonstrüksiyon ii) antioksidan sistem enzimleri üzerine yaptığı etki serbest oksijen radikallerini arttırmasıdır. CsA uygulanan deneklere antioksidan özelliği olan Vit E ve Vitamin C ile birlikte kalsiyum kanallarını bloke ederek vazodilatatör etkinlik gösteren verapamili vererek, farklı deney gruplarında böbrek korteksindeki histopatalojik değişiklikleri değerlendirmek ve bu değişikliklere antioksidan ve vazodilatatör ajanların tek tek ve birlikte verildiklerindeki etkilerini araştırmak amacıyla bu çalışmayı yaptık. Materyal ve Metod: 25 sıçan; kontrol grubu, siklosporin A (CsA) verilen grup, CsA+ vitamin EveC verilen grup, CsA+verapamil verilen grup ve CsA+vitamin+verapamil verilen grup olmak üzere beş gruba ayrıldı. 10 gün boyunca CsA nazogastrik sonda ile oral olarak 50 mg/kg dozunda, E vitamini 150 mg/kg dozunda intramüsküler olarak; C vitamini 200 mg/kg dozunda intraperitoneal olarak, verapamil 0.5 mg/kg dozunda intramüsküler olarak verildi. Çalışmanın sonunda sıçanların kanları ve böbrek dokuları eter anestezisi altında alındı. Böbrek dokusu %10'luk formolde tespit edildi. Rutin histolojik takip ile bloklanan dokulardan 5|jm 'lik kesitler alındı ve hematoksilen-eozin ile boyanarak değerlendirildi. Bulgular: Çalışmamızın sonunda CsA verilen grupta histolojik olarak belirgin yapısal değişiklikler ortaya çıktı. Bu değişiklikler CsA + vitamin EveC verilen grup ve CsA + verapamil verilen gruplarda kısmen düzelmekle birlikte; normal histolojik yapıya en yakın görünüm CsA + vitamin + verapamil alan grupta görüldü. Ayrıca böbrek dokusunda antioksidan enzimlerden glutatyon proksidaz ve katalazda en belirgin yükselme ve böbrek fonksiyon testlerinden BUN ve kreatinin de en belirgin düzelme de bu grupta izlendi. Sonuç: CsA'nın yaptığı nefrotoksisitenin önlenmesi için; verapamil, vitamin E ve C'nin birlikte kullanılmasının daha faydalı olacağı kanaatindeyiz.
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REFERENCES

References: 

1. Dieperink H. Cylosporin A nephrotoxicity. Dan.Med.Bull. 36:235-248, 1989
2.
Benne
t WM. The nephrotoxicity of immunusupressant drugs. ClinNephrol, 43:s3-7, 1995
3. Dieperink H, Frandsen NE, Kemp E. Cyclosporin A. Bright prospects for organ transplantation?. Ugeskr Laeger. 145:36:2749-52,1983
4. Borel JF,Feurer C, Gubler HU, Stahelin H. Biological effects of cyclosporin A: a new antilymphotic agent, AgentsActions, 43:179-186,1976
5. Calne RY, White DJ, Thiru S, Evans DB, McMaster P, Dunn DC, Craddock GN, Pentlow BD, Rolles K. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet, 2:1323-1327,1978
6. Durkan am,Hodson EM,Willis NS, Craig JC. Ýmmunsupressive agents in childhood nephrotic syndrome: a meta-analysis ofrandomized controlled trials. Kidneyint. 59,1919-1927, 2001
7. High KP. The antimicrobial activities ofcyclosporin, FK506 andrapamycin. Transplantation. 57,1689-1700, 1994
8. Thiel G, Landmann J, Mihatsch MJ: Ciclosporin:acute or chronic toxicity, or rejection?AM Hassaballah (ed), Excerptamedica, Amsterdam,122-133, 1987
9. Murray BM, Paller MS, Ferris TF: Effects of CsA administration on renal hemodynamic in conscious rats. Kidney Int, 28:767-74,1985
10. Strzelecki T, Kumar S, Khaulý R, et al: Impairment by cyclosporine ofmembrane-mediated functions in kidney mitochondria. Kidney Int, 34:234-240,1988
11. Orugun EO, Smart LM, Whiting PH: The effect of calcium blockade with verapamil on experimental cyclosporinenephrotoxicity. TransplantProc 1991, 23:1:354-5.
12. Dawidson I, Rooth P, Fry WR, et al: Preventation of acute cyclosporine induced renal blood inhibition and improved immunosuppresion with verapamil. Transplantation, 48:4:575-80,1989
13. Dieperink H, Leyssac PP, Starklint H, et al: Nephrotoxicity ofcyclosporine A: a lithium clearence and micropuncture study in rats. Eur J Clin Invest 1986, 16:69.
14. Salducci MD, Chauvet-Monges AM, Berland Y, et al: The restoration ofATP synthesis may explain in protective effect ofcalcium antagonists against CyclosporineAnephrotoxicity. Life Sciences, 50:2053¬58,1992
15. Duriebe VA, Okanmah A, Blyden GD. Effect ofCsA on rat liver and kidney glutathione content. Pharmacology, 39:205-212,1989
16. Ýnselmann G, Hannemann J, Baumann K. Cylosporin A induced lipid peroxidation and influence on glucose 6 phosphatase in rat hepatic and renal microzomes. Res Common Chem Pathol Pharmacol, 68:189¬203,1990
17. Wang CH, Salahudeen AK. Cylosporin nephrotoxicity: attenuation by an antioxidant inhibitor oflipid peroxidation in vitro and in vivo. Transpantation 58:940¬946, 1994
18. Ýnselmann G, Baumann K. Effect ofcyclosporin A on accumulation oftetraethylammonium and p-aminohippurat and on lipit peroxidation in rat renal microzomes and cortical slices. Ren Fail.12:165-169, 1990
19. MaCay PB, King MM: Vitamin E: Its role as a biological free radical scavenger and its relationship to the microsomal mixed-function oxidase system. Vitamin E, New York, 1980, Marcel Dekker Inc, pp:289-317.
20. Pascoe GA, Reed DJ: Cell calcium, vitamin E and the thiol redox system in cytotoxicity. Free Radical Biology and Medicine, 6:209-24,1989
21. Marubayashi S, Dohi K, Ochi K, et al: Role ofthe free radicals in ischemic rat liver cell injury: preventation ofdamage by a -tocopherol administration. Surgery , 99:2:184-191,1986
22. Kunisaki M, Umeda F, Inoguchi T, et al: Vitamin E binds to spsific binding sites and enhances prostacyclin production by cultured aortic endotelial cells. Thromb Haemost,68:774,1992
23. Lunec J, Blake D, Oxygen Free Radicals. Their relevance to disease processes . In : Cohen RD, Lewis B, Albert KGMM. The Metabolic and Moleculer Basis ofAcquired Disease. Balliere Tindall, London. 189¬212, 1990.
24. Jialal I, Fuller CJ. Oxidized LDL and antioxidants . ClinCardiol. 16:1-9,1993.
25. Lawry OH, Rosebrough NJ,Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 182:265,1951.
26. Mihatsch Mj, Thiel G, Basler V, Ryffel B, et all. Morphological patterns in cyclosporin-treated renal transplantrecipients. TransplantProc,4(suppl 1):101-16,1985
27. Thiel G. Experimental cyclosporin nephrotoxicity. Clin Nephrol, 25(suppl 1):205-10,1986
28. Zhong Z,Arteel GE, Connor HD, et all. Am J Physiol, 275:F595,1998
29. Yang JJ, Finn WF. Ren Fail, 20:85,1998
30.
Kadayýfç
ý A. Dahiliye. 1.baský, Atlas Kitapçýlýk, Ankara, 199-297, 2001
31. Hebert SC,Kriz W. Diseases ofkidney. Schrier RW, Gottschalk CW (ed), vol1:3-37,1997
32. Tisher CC, Madsen KM. Anatomy ofthe kidney. Brenner BM (ed), The Kidney,3:62,1996
S.D.Ü. Týp pak.
Derg
. 2005:12(4)/ 28-35
Ural, Siklosporinin böbrek toksisitesine Vitamin C, E ve verapamilin etkisi
35
33. Venkatachalam MA, Bernard DB, Donohoe JF. ischemic damage and repair in the rat proximal tubule. Kidneyint, 14:31-49,1978
34. Kim JY, Suh KS. Light microscobic and electron microscobic feautures ofCyA nephrotoxicity in rats. J Kor MED Sci,10:5:352-59,1995
35. Massicot F, Thevenin M, Martin C, et all, Effect of cyclosporin on kidney glutathion mrtabolizm ang ccytocrom p450 in the rabbit. Drug chem toxicol,17:449-62,1994
36. Ýnselmann G, Blank M, Baumann K. Cyclosporin induced lipit peroxidation in microsomes ofrat kidney. Res. Commun. ChemPatholPharmacol,62:207-20,1988
37. Walker PD, Das C, Shah SV. Cyclosporin A induced lpid peroxidation in renal cortical mitocondria. Kidney int, 29:311,1986
38. Ýnselmann G, Barth A, Engemann R, Heidemann H. Cyclosporin A induced lipid peroxidation in human liver microsomes. Eur J Clin Ýnvest,21:461-65,1991
39. Ketterer B, Beale D, Meyer D,. The structure ofmultiple functions ofglutathiontransferases. Biochem Soc
Trans, 10:82-84, 1982
40. Mun Kc, Suh SI. Effect ofmelatonin on renal function in cyclosporin nephrotoxicity. Transplantation proc, 32:1919-20,2000
41. Durak I, Karabacak HI, Buyukkocak S, Cimen MY, Kacmaz M ve ark. Ýmpaired antioxidant defens system in the kidney tissues from rabbits treated with cyclosporin: Protective effects ofvitamins E and C. Nephron,78(2):207-11,1998
42.
Özdemi
r M, Aktan Y, Dündar E, Çolak Ö, Cingi ÝM, Tel N. Siklosporin A nefrotoksisitesine karþý vitamin E'nin etkisi. Çukurovaüniv Týp Fak Derg, 23:2:67¬71,1998
43.
Kayaal
p O. Týbbi Farmakoloji. Vitaminler. Cilt 2, 9. Baský, Hacettepe Taþ Kitabevi, 1541-1575, 2000
44. Faustman DL, Hauptfeld V, Davie JM, Lacy PE. Ýncrase in urinary thromboxane B2 in rats caused by cyclosporine. Transplant,40:2:214-17, 1985
45. Petric R, Freeman D, Wallace C, et all. Amelioration of experimental cyclosporin A nephrotoxicity by calcium channel inhibition. Brief communications, 1103-1105,1992
46. English J, Evan A, Houghton DC, Bennet WM. Cyclosporin induced acute dysfunction in the rat. Transplant,44:1:14-17,1986
47. Bokemeyer D, Friedrichs U, Backer A, et all. Cyclosporin A Enhances total cell calcium independent ofNA-K-ATPaz in vasculer smooth muscle cells. Clin Ýnvestig, 72:12:992-5,1994
48. Bhardwaj R, Moore PK. The effect ofarginin and NO on resistance blood vessels ofthe perfused rat kidney. Br J Pharmacol, 97:739-44,1989
49. Darlametsos IE, PapanikalaouN, Varanos DD. Effect
ofnifedipine in CyA induced nephrotoxicity in rats. Prostaglandins leukotriens and essential Fatty
acids,63:5:263-69,2000
50. L'Azou B, Lagroye I, Plande J,et all. Protective effect ofverapamil and dopamine against CyA induced vazoconstruction in isolated glomeruli in rats. Presse Med,21:41:2021-3,1992
51. Abraham JS, Bentley FR, Garrison RN. Calcium channel blockade in rats with cyclosporin induced vasoconstrýction. Ýnvest Surg, 6:5:401-12,1993

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