Kefirin Sıçanlarda Oluşturulmuş Siklofosfamid Toksisitesi Üzerine Myeloprotektif Ve Hematoprotektif Etkileri

Yıl 2021, Cilt: 6 Sayı: 2, 77 - 82, 02.08.2021

Songül Çetik Yıldız , Gülay Gözüoğlu

https://doi.org/10.25000/acem.903843

Cited By: 6

Öz

Amaç: Kefir, bakteri ve maya karışımı içeren kefir taneleri ile sütten üretilen egzotik tada sahip probiyotik ve prebiyotik bir içecektir. CP gibi kanser kemoterapisi için kullanılan ilaçların kullanımı, genellikle, çok sayıda organda istenmeyen şiddetli akut toksik yan etkiler yüzünden sınırlıdır. Bu amaçla bu çalışmada antitümör ve antioksidan özellikleri iyi bilinen doğal bir probiyotik olan kefirin CP nedenli hemotoksisite ve myelotoksisite üzerine koruyucu etkileri araştırılmıştır.
Gereç ve Yöntem: Grup 1(kontrol), grup 2; tek doz 150 mg/kg/b.w/i.p CP, Grup 3; 5 mg /kg / b.w kefir, grup 4; 5 mg/kg/b.w+150 mg/kg/b.w/i.p CP, grup 5; 10 mg/kg/b.w kefir, Grup 6; 10 mg /kg/b.w kefir+150 mg/kg/b.w/i.p CP. Kefir gavaj yöntemiyle 12 gün boyunca verildi. CP ise 12. Gün tek doz olarak verildi. Deneyin sonunda tüm sıçanlar disekte edilerek kan ve kemikiliği örnekleri alındı.
Bulgular: Periferik kan hücreleri (lökosit, trombositler, RBC ve Hb) ve kemik iliği çekirdekli hücre düzeylerinin CP verilen grupta düştüğü, CP+kefir verilen gruplarda ise yükseldiği ve kontrole yaklaştığı görülmüştür.
Sonuç: Sonuçlarımız antitümör, antioksidan ve sitoprotektif özellikleri olan kefirin kan ve kemik iliği hücrelerini CP hasarına karşı koruduğunu göstermiştir.

Anahtar Kelimeler

Kefir, Siklofosfamid, Myelotoksisite, Hemotoksisite, rat

Destekleyen Kurum

Mardin Artuklu Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü

Proje Numarası

MAÜ.BAP.20.SHMYO.004

Myeloprotective and hematoprotective role of kefir on cyclophosphamide toxicity in rats

Öz

Aim: Kefir is a probiotic/prebiotic drink with an exotic flavor, which has been traditionally produced with fermented milk and kefir grains containing a mixture of bacteria and yeast. Cyclophosphamide (CPx), are generally limited due to numerous unwanted and severe acute toxic side-effects. For this purpose, the cell-protective effects of kefir, a natural probiotic known for its antitumor and antioxidant properties, on CPx-induced hemotoxicity and myelotoxicity were investigated.
Methods: Group 1 using as control. Group 2 were administered a single dose of 150mg/kg CPx while Group 3 and 5 were given 5 and 10mg/kg kefir. Group 4 and 6 were given 5 and 10mg/kg kefir+150mg/kg CPx. While kefir was administered to the rats for 12 days, CPx was administered as single-dose on the 12th day.
Results: The DPPH results show that kefir possesses high antioxidant activity. It was observed that the leukocytes, thrombocytes, erythrocytes, hemoglobin, hematocrit and bone marrow nucleated cell levels decreased in the group that was administered only CPx, and increased relatively in the groups that were administered CPx+kefir, drawing close to the control.
Conclusion: The results of the present study also showed that kefir demonstrated antioxidant and cytoprotective activity, protecting blood and bone marrow cells against CPx-induced damage.

Anahtar Kelimeler

Kefir, cyclophosphamide, myelotoxicity, hemotoxicity, rat

Proje Numarası

MAÜ.BAP.20.SHMYO.004

Kaynakça

• 1. Ender G, Karagözlü C, Yerlikaya O, Akbulut N. Dünyada ve Türkiye'de tüketimi artan fermente süt içecekleri. Türkiye Bolu 9. Gıda Kongresi. 2006;149-52.
• 2. Corthesy B, Gaskins HR, Mercenier A. Cross-talk between probiotic bacteria and the host immune system. J Nutr. 2007; 137(3-2):781-90.
• 3. Ozyurt VH, Otles S. Prebiyotikler: Metabolizma için önemli bir gıda bileşeni. Akademik Gıda. 2014; 12(1):115-23.
• 4. Otles S, Cagindi O. Kefir: A probiotic dairy-composition, nutritional and therapeutic aspects. Pak J Nutr. 2003; 2(2):54-9.
• 5. Walsh AM, Crispie F, Kilcawley K, O'Sullivan O, O'Sullivan MG, Claesson MJ, et al. Microbial succession and fla¬vor production in the fermented dairy beverage kefir. mSystems. 2016; 4:1(5).
• 6. Purutoglu K, İspirli H, Yüzer MO, Serencam H, Dertli E. Diversity and functional characteristics of lactic acid bacteria from traditional kefir grains. Int J Dairy Technol. 2019; 73(1):57-66.
• 7. Wszolek M, Tamime A, Muir D, Barclay M. Properties of kefir made in Scotland and Poland using bovine, caprine and ovine milk with different starter cultures. LWT- Food Sci Technol. 2001; 34:251-61.
• 8. Leite AMO, Miguel MAL, Peixoto RS, Rosado AS, Silva JT, Paschoalin VMF. Microbiological, technological and therapeutic properties of kefir: a natural probiotic beverage. Braz J Microbiol. 2013; 44(2):341-9.
• 9. Koroglu O, Bakır E, Uludag G, Koroğlu S. Kefir and health. KSU J Agric Nat. 2015; 18(1):26-30.
• 10. Ahmed Z, Wang Y, Ahmad A, Khan ST, Nisa M, Ahmad H, Afreen A. Kefir and health: a contemporary perspective. Crit Rev Food Sci Nutr. 2013; 53:422-34.
• 11. Hacioglu G, Kurt G. Consumers’ Awareness, Acceptance and Attitudes towards Functional Foods: A Research in Izmir City. Business and Economics Res. J 2012; 3(1):161-71.
• 12. Adiloglu AK, Gönülateş N, İşler M, Şenol A. The effect of kefir consumption on human immune system: A cytokine study. Mikrobiyoloji Bülteni. 2013; 47:273-81.
• 13. Davras F, Tas TK, Guzel-Seydim ZB. Immunological effects of Kefir produced from Kefir grains versus starter cultures when fed to mice. Funct Foods Health Dis. 2018; 8(8):412-23.
• 14. Guven A, Gulmez M. The effect of kefir on the activities of GSH-Px, GST, CAT, GSH and LPO levels in carbon tetrachloride-induced mice tissues. J Vet Med B Infect Dis Vet Public Health. 2003; 50(8):412-6.
• 15. Elsayed EA, Farooq M, Dailin D, El-Enshasy HA, Othman NZ, Malek R, et al. In vitro and in vivo biological screening of kefiran polysaccharide produced by Lactobacillus kefiranofaciens. Biomed Res. 2017; 28 (2):594-600.
• 16. Yildiz SC, Demir C, Cengiz M, Ayhanci A. Protective properties of kefir on burn wounds of mice that were infected with S. aureus, P. auroginasa and E. coli. Cell Mol Biol. 2019a; 65:7.
• 17. Kalaycioglu ME, Lichtin AE, Andrese SW, Tuason L, Bolwell BJ. High-dose busulfan and cyclophosphamide followed by autologous bone morrow transplantation and/or peripheral blood progenitor cell rescue for metastatic breast cancer. Am. J Clin Oncol. 1995; 18(6):491-4.
• 18. Cavalletti E, Tofanetti O, Zunino F. Comparision of reduced glutathione with 2-mercaptoethane sulfonate to prevent cyclophosphamide induced urotoxicity. Cancer Lett. 1986; 32:1-6.
• 19. Kumar KBH, Kuttan R. Chemoprotective activity of an extract of phyllanthus amarus against cyclophosphamide-induced toxicity in mice. Phytomed. 2004; 12(6-7):494-500.
• 20. Shirani K, Hassani FV, Razavi-Azarkhiavi K, Heidari S, Zanjani BR, Karimi G. Phytotrapy of cyclophosphamide-induced immunosuppression. Environ Toxicol Pharmacol. 2015; 39:1262-75.
• 21. Roy P, Waxman DJ. Activation of oxazaphosphorines by cytochrome P450: application to gene-directed enzyme prodrug therapy for cancer. Toxicol in Vitro 2006; 20:176-86.
• 22. Kern JC, Kehrer JP. Acrolein-induced cell death: a caspase influenced decision between apoptosis and oncosis/necrosis. Chem Biol Interact. 2002; 139(1):79-95.
• 23. MacAllister SL, Martin-Brisac N, Lau V, Yang K, O’Brien PJ. Acrolein and chloroacetaldehyde: an examination of the cell and cell-free biomarkers of toxicity. Chem Biol Interact. 2013; 202(1):259-66.
• 24. Mythili Y, Sudharsan PT, Selvakumar E, Varalakshmi P. Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced oxidative cardiac injury. Chem Biol Interact. 2004; 151(1):13-9.
• 25. Abraham P, Isaac B. Ultrastructural changes in the rat kidney after single dose of cyclophosphamide-possible roles for peroxisome proliferation and lysosomal dysfunction in cyclophosphamide-ınduced renal damage. Hum Exp Toxicol. 2011; 30:1924-30.
• 26. Yildiz SC, Keskin C, Sahinturk V, Ayhanci A. A Histopathological, immunohistochemical and biochemical investigation on the in vitro antioxidant, myeloprotective, hematoprotective and hepatoprotective effects of Hypericum triquetrifolium seed extract against cyclophosphamide-induced toxicity. Braz Arch Biol Technol. 2019b; 62 (4):e19180345.
• 27. Senthilkumar S, Devaki T, Manohar BM, Babu MS. Effect of squalene on cyclophosphamide-induced toxicity. Clinica Chimitica Acta 2006; 364(1-2):335-42.
• 28. Marshall V. Observations on the structure of kefir grains and the distribution of the microflora. J Appl Bacteriol. 1984; 57:491-7.
• 29. Kubo M, Odani T, Nakamura S, Tokumaru S, Matsuda H. Pharmacological study on kefir-a fermented milk product in Caucasus. I. On antitumor activity (1) (in Japanese). Yakugaku Zasshi. 1992; 112:489-95.
• 30. Matsuu M, Shichijo K, Okaichi K, Wen CY, Fukuda E, Nakashima M, et al. The protective effect of fermented milk kefir on radiation-induced apoptosis in colonic crypt cells of rats. J Dairy Res. 2003; 44(2):111-5.
• 31. Tomar O, Çağlar A, Akarca G. Kefir ve sağlık açısından önemi. AKU J Sci. 2017; 027202:834-853.
• 32. Wang H, Sun X, Song X, Guo M. Effects of kefir grains from different origins on proteolysis and volatile profile of goat milk kefir. Food Chem. 2020; 339:128099
• 33. Alpkent Z, Kucukcetin A. Farklı sıcaklıklarda muhafaza edilen kefirlerin duyusal, fiziksel, kimyasal ve mikrobiyolojik özelliklerinde meydana gelen değişimler. Süt Mikrobiyolojisi ve Katkı Maddeleri, VI. Süt ve Süt Ürünleri Sempozyumu Tebliğler Kitabı, Editör: Mehmet Demirci, Tekirdağ, s. 2000; 363-373.
• 34. Guzel-Seydim ZB, Wyffels JT, Seydim AC, Greene AK. Turkish kefir and kefir grains: microbial enumeration and electron microscobic observation. Int J Dairy Technol. 2005; 58:25-29.
• 35. Arslan S. A review: chemical, microbiological and nutritional characteristics of kefir. CyTA-J Food. 2015; 13:340-5.
• 36. Grishina A, Kulikova I, Alieva L, Dodson A, Rowland I, Jin J. Antigenotoxic effect of kefir and ayran supernatants on fecal water induced DNA damage in human colon cells. Nutr Cancer. 2011; 63(1):73-9.
• 37. Ghoneum M, Gimzewski J. Apoptotic effect of a novel kefir product, PFT, on multidrug-resistant myeloid leukemia cells via a hole-piercing mechanism. Int J Oncol. 2014; 44(3): 830-7.
• 38. Akbay GD. Kefirin antikarsinojenik rolü. Cumhuriyet Üniv Sağ Bil Enst Derg 2020; (5)2:73-82.
• 39. Guzel-Seydim ZB, Seydim AC, Greene AK. Comparison of amino acid profiles of milk, yoğurt and Turkish kefir. Milchwissenschaft. 2003; 58(3-4):158-60.
• 40. Moore FR, Urda GA, Krishna G, Theiss JC. An invivo/invitro method for assessing micronucleus and chromosome aberration induction in rat bone morrow and spleen. 1. Studies with cyclophosphamide. Mutat Res., Environ Mutagen Relat Subj. 1995; 335(2):191-9.
• 41. Habibi E, Shokrzadeh M, Chabra A, Naghshvar F, Keshavarz-Maleki R, et al. Protective effects of Origanum vulgare ethanol extract against cyclophosphamide-induced liver toxicity in mice. Pharm Biol. 2015; 53(1):10-5.
• 42. Zarei M, Shivanandappa T. Amelioration of cyclophosphamide-induced hepatotoxicity by the root extract of Decalepishamiltonii in mice. Food Chem Toxicol. 2013; 57:179-84.
• 43. Rosa DD, Dias MS, Grześkowiak LM, Reis SA, Conceiçao LL, Peluzio MCG. Milk Kefir. Nutr Res Rev. 2017; 30(1):82-96.
• 44. Nafees S, Rashid S, Ali N, Hasan SK, Sultana S. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFkB/MAPK pathway. Chem Biol Interact. 2015; 231:98-107.
• 45. Mansour HH, El Kiki SM, Hasan HF. Protective effect of N-acetylcysteine on CP-induced cardiotoxicity in rats. Environ Toxicol Pharmacol. 2015; 40:417-22.
• 46. Yang Y, Xu S, Xu Q, Liu X, Gao Y, Steinmetz A, et al. Protective effect of dammarane sapogenins against chemotherapy-induced myelosuppression in mice. Exp Biol Med. 2011; 236:729-35.
• 47. Trasler JM, Hales BF, Robaire B. A timecourse study of chronic paternal cyclophosphamide treatment in rats: Effects on pregnancy outcome and the male reproductive and hematologic systems. Biol Reprod. 1987; 37(2):317-26.
• 48. Cengiz, M. Hematoprotective effect of boron on cyclophosphamide toxicity in rats. Cell Mol. Bio. 2018; 64(5), 62-5.
• 49. Cengiz M, Yeşildağ Ö, Ayhanci A. Siklofosfamid Nedenli Hematoksisite Üzerine Karvakrolün Sitoprotektif Etkileri. Turc J Agric Res. 2018; 5(2), 125-30.