Ratlarda Cyclophosphamide ile İndüklenen Nefrotoksisitede Bazı Hematolojik Parametreler ve Böbreğin Histopatolojisi Üzerine Naringinin Protektif Etkileri

Öz

Bu çalışmada cyclophosphamide (CYP) ile indüklenen nefrotoksisitede Naringin’in protektif etkilerinin araştırılması

amaçlanmıştır. Araştırmamızda yaklaşık 200-250 g ağırlığında, 40 adet erkek erişkin Sprague Dawley ırkı rat kullanıldı ve 5

grup oluşturuldu. Hematolojik ve biyokimyasal parametrelerin ölçümü Abocus Junior Vet5 hemogram cihazında rat modunda

ve Modüler PP otoanalizöründe yapıldı. CYP’li gruplarda alyuvar sayısı, akyuvar sayısı, hematokrit değer, trombosit sayısı ve

lenfosit (%) düşmesine rağmen, nötrofil (%) ve monosit (%) miktarı arttı (P<0.05). CYP gruplarında potasyum (K) ve sodyum

(Na) düzeyinde istatistiki anlamda (P<0.05) düşüş görülürken, fosfor (P), magnezyum (Mg), klor (CI) ve kalsiyum (Ca)’da düşüş

görülmedi. Böbrek fonksiyon testlerinden glikoz, kreatin ve ürik asit seviyeleri istatistiki açıdan anlamlı bir şekilde yükselirken

(P<0.05), üre, BUN ve laktat dehidrojenaz (LDH) değerlerindeki yükseliş ise anlamsız bulundu. Histopatolojik incelemede;

CYP’nin etkisiyle böbrek dokusu tubul epitellerinde şiddetli hidropik dejenerasyon ve koagulasyon nekrozu, Bowman

kapsülünde dilatasyon, intersitisyel damarlarda ve glomeruluslarda hiperemi belirlendi. Böbrekte oluşan bu hasarların

Naringin’in sitoprotektif etkisiyle doza bağlı olarak azaldığı saptandı. Naringin’in farklı dozlarının, CYP’nin olumsuz etkilerini

ve nefrotoksisiteyi baskılama etkisine sahip olduğu tespit edildi.

Anahtar Kelimeler

• CYP,Kan Parametreleri,Naringin,Nefrotoksisite,Rat.

The Protective Effects of Naringin on Some Blood Paremeters and Kidney Histopathology in Cyclophosphamide Induced Nephrotoxicity in Rats

Öz

In this study, it was aimed to investigate the protective effects of Naringin on nephrotoxicity by Cyclophosphamide

(CYP)-induced rats. In our study, forty male adult Sprague Dawley rat weighing approximately 200-250 g were used and 5

gropus formed. Measurement of hematologic and biochemical parameters were done in the rat mode on the Abocus Junior

Vet 5 hemogram and on Modular PP autoanalyzer instruments. In the CYP groups, Neutrophil (%) and monocyte (%) increase

despite red blood cell count, white blood cell count, hematocrit value, thrombocyte count and lymphocyte (%) decrease

(P<0.05). While there were a decrease in potasium and sodium levels (P<0.05), but no decrease in other parameters such as

phosphorus, magnesium, chlorine and calcium. Altough glucose, creatinine and uric acid levels from renal function tests were

statistically significantly increased at (P<0.05), the increase in urea, BUN and lactate dehydrogenase (LDH) values were not

significant. In the histopathological exemination; It was determined that severly hydropic degeneration and coagulation

necrosis in tubule ephitelia, dilatation in Bowman capsule, hyperemia in interstitial vein and glomerulus of kidney tissue by

the effects of CYP. These damages in the kidney were found to be reduced as dose-dependent due to cytoprotective effects

of Naringin. It was determined that different doses of Naringin suppress nephrotoxicity and the negative effect of CYP.

Anahtar Kelimeler

• CYP,Heamatological Parameters,Naringin,Nephrotoxicity,Rat

Kaynakça

1. 1. Nasrin S., Masuda E., Kugaya H., Ito Y., Yamada S., 2013. Improvement by phytotherapeutic agent of detrusor overactivity, down-regulation of pharmacological receptors and urinary cytokines in rats with cyclophosphamide induced cystitis. J Urol, 189, 1123-1129.
2. 2. Miller CR., Ruppert AS., Fobare S., Chen TL., Liu C., Lehman A., Blachly JS., Zhang X., Lucas DM., Grever MR., Tallman MS., Flinn IW., Rassenti LZ., Kipps TJ., Sampath D., Coombes KR., Hertlein EK., 2017. The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia. Oncotarget, 8, 25942-25954.
3. 3. Cerulla N., Arcusa A., Navarro JB., Garolera M., Enero C., Chico G., Fernandez Morales L., 2017. Role of taxanes in chemotherapy-related cognitive impairment: A prospective longitudinal study. Breast Cancer Res Treat,162, 1-9.
4. 4. Clowse ME., Harward L., Criscione Schreiber L., Pisetsky D., Copland S., 2012. Anti Müllerian hormone: A better marker of ovarian damage from cyclophosphamide. Arthritis Rheum, 64, 1305-1310.
5. 5. Anderson D., Bishop JB., Garner RC., Ostrosky Wegman P., Selby PB., 1995. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res, 330, 115-181.
6. 6. Atalay F., Gülmez Ö., Özsancak AU., 2014. Cardiotoxicity following cyclophosphamide therapy: a case report. J Med Case Rep, 8, 252.
7. 7. Kanno TYN., Sensiate LA., Paula NA., Salles MJS., 2009. Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice. Braz J Pharm Sci, 45, 313-319.
8. 8. Nizamlıoğlu NM., Nas S., 2010. Meyve ve sebzelerde bulunan fenolik bileşikler; yapıları ve önemleri. EJFT, 2010, 5, 25-35.

9. 9. Jagetia GC., Reddy TK., Venkatesha VA., Kedlaya R., 2004. Influence of naringin on ferric iron induced oxidative damage in vitro. Clin Chim Acta, 347, 189-197.
10. 10. Zhou X., Zhang P., Zhang C., Zhu Z., 2010. Promotion of bone formation by naringin in a titanium particle induced diabetic murine calvarial osteolysis model. J Orthop Res, 28, 451-456.
11. 11. Kim SY., Kim HJ., Lee MK., Jeon SM., Do GM., Kwon EY., Cho YY., Kim DJ., Jeong KS., Park YB., 2006. Naringin time dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high fat and high cholesterol diet. J Med Food, 9, 582-586.
12. 12. Choe SC., Kim HS., Jeong TS., Bok SH., Park YB., 2001. Naringin has an antiatherogenic effect with the inhibition of inter cellular adhesion molecule 1 in hypercholesterolemic rabbits. J Cardiovasc Pharmacol , 38, 947-955.
13. 13. Camargo CA., Gomes Marcondes MC., Wutzki NC., Aoyama H., 2012. Naringin inhibits tumor growth and reduces interleukin 6 and tumor necrosis factor alpha levels in rats with Walker 256 carcinosarcoma. Anticancer Res , 32, 129-133.
14. 14. Liu Q., Lu L., Xiao M., 2012. Cell surface engineering of αlrhamnosidase for naringin hydrolysis. Bioresour Technol, 123, 144 149.
15. 15. Sinanoglu O., Yener AN., Ekici S., Midi A., Benli Aksungar F., 2012. The Protective Effects of Spirulina in Cyclophosphamide Induced Nephrotoxicity and Urotoxicity in Rats. Basic Transl Sci, 80, 1392-1392.
16. 16. Abraham P., Isaac B., 2010. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats. Hum Exp Toxicol, 30, 616-623.
17. 17. Besse A., Clapp GD., Bernard S., Nicolini FE., Levy D., Lepoutre T., 2017. Stability analysis of a model of ınteraction between the ımmune system and cancer cells in chronic myelogenous leukemia. Bull Math Biol, 1-27.
18. 18. Erkurt MA., Kuku İ., Kaya E., Aydoğdu İ., 2009. Kanser kemoterapisi ve böbrek. İnönü Univ Tıp Fak Derg, 16, 63-68.
19. 19. Ernest E., Girndt M., Pliquett RU., 2014. A case of granulomatosis with polyangiitis complicated by cyclophosphamide toxicity and opportunistic infections: choosing between Scylla and Charybdis. BMC Nephrol, 15, 28.
20. 20. Ghosh S., Misro M., Das UB., Maiti R., Debnath JM., Ghosh D., 2001. Effect of human chorionic gonadotrophin co administration on ovarian steroidogenic and folliculogenic activities in cyclophosphamide treated albino rats. Reprod Toxicl, 15, 221-225.
21. 21. Kenney LB., Laufer MR., Grant FD., Grier H., Diller L., 2001. High risk of infertility and long term gonadal damage in males treated with high dose cyclophosphamide for sarcoma during childhood. Cancer, 91, 613-621.
22. 22. Hochster H., Wasserheit C., Speyer J., 1995. Cardiotoxicity and cardioprotection during chemotherapy. Curr Opin Oncol, 7, 304-309.
23. 23. Braverman AC., Antin JH., Plappert MT., Cook EF., Lee RT., 1991. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol, 9, 1215-1223.
24. 24. Çelebi F., Gelen V., Çınar A., Şengül E., 2014. The effect of rutin on overactive contractility of bladder smooth muscle in the model of cyclophosphamide-induced cystitis in rats. The FASEB Journal, 28, 690-15.
25. 25. Şengül E., Gelen V., Gedikli S., Özkanlar S., Gür C., Çelebi F., Çınar A. 2017. The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats. Biomed Pharmacother, 92, 303-307.
26. 26. Gelen V., Şengül E., Gedikli S., Çelebi F., Çınar A., Kara A., Özkanlar S., Gür C., 2016. The effects of quercetin on cyclophosphamide-induced cardiotoxicity in rats. Acta Physiol, 218, 14-15.
27. 27. Yılmaz B., 2000. Fizyoloji. 2. baskı, Feryal Matbaacılık, Ankara.
28. 28. Konuk T., 1981. Pratik Fizyoloji I. 2. baskı, Ankara Üniversitesi Basımevi, Ankara.
29. 29. Comba B., Mis L., Comba A., Çınar A., Tas A., 2014. Deneysel olarak diabet olusturulmus ratlarda yara ıyilesmesinde sildenafil sitratın bazı hematolojik parametrelere ve mineral maddelere etkisi. Atatürk Üniversitesi Vet Bil Derg, 9, 180-186.
30. 30. Gencer GY., Çınar A., Comba B., 2015. Stresin ratlarda bazı karaciğer enzimleri AST, ALT, ALP üzerine etkilerinin araştırılması. Atatürk Üniversitesi Vet Bil Derg, 10, 21-26.
31. 31. Yıldırım S., Oto G., Comba B., Ekın S., Cınar A., 2017. An investıgation of the protective effects of resveratrol on some biochemical parameters and histopathological findings in experımentally-induced chronic flurosis in rats. Fluoroide, 50, 367-375.
32. 32. Maaroufi K., Chekir L., Creppy EE., Ellouz F., Bacha H., 1996. Zearalenone induces modifications of haematological and biochemical parameters in rats. Toxicon, 34, 535-540.
33. 33. He ML., Wang YZ., Xu ZR., Chen ML., Rambeck WA., 2013. Effect of dietary rare earth elements on growth performance and blood parameters of rats. J Anim Phsiol Anim Nutr, 87, 229-235.
34. 34. Comba B., Çınar A., Comba A., Gencer GY., 2016. Sıçanlarda ACTH uygulamasının böbrek fonksiyon testleri, elektrolitler ve hematolojik parametreler üzerine etkileri. Ankara Üniv Vet Fak Derg, 63, 229-233.
35. 35. Belge F., Çınar A., Selçuk M., 2003. Effects of stress produced by adrenocorticotropin (ACTH) on the lipid peroxidation and some antioxidants in vitamin C treated and nontreated chickens. S Afr J Anim Sci, 33, 201-205.
36. 36. Schneider PL., Beede DK., Wilcox CJ., 1988. Nycterohemeral patterns of acid-base status, mineral concentrations and digestive function of lactating cows in natural or chamber heat stress environments. J Anim Sci, 66, 112-125.
37. 37. Yıldırım S., Çelıkezen FC., Oto G., Sengül E., Bulduk M., Cinar A., 2017. An investigation of protective effects of litium borate on blood and histopathological parameters in acute cadmium-induced rats. Biol Trace Elem Res, 1-6.
38. 38. Noyan A., 2011. Yaşamda ve Hekimlikte Fizyoloji, 10. Baskı., 606-620, Palme Yayıncılık, Ankara.
39. 39. Rehman MU., Tahir M., Ali F., Qamar W., Lateef A., Khan R., Quaiyoom A., Oday-O-Hamiza., Sultana S., 2012. Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid. Mol Cell Biochem, 365, 119-127.
40. 40. Amien AI., Fahmy SR., Abd-Elgleel FM., Elaskalany SM., 2015. Renoprotective effect of Mangifera indica polysaccharides and silymarin against cyclophosphamide toxicity in rats. JOBAZ, 72, 154-162.