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Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats

Yıl 2024, Cilt: 24 Sayı: 06, 1275 - 1284

Öz

To evaluate kefir, a naturally occurring fermented dairy product, with pharmacological and therapeutic qualities including antioxidant, anti-apoptotic, and anti-inflammatory effects against cyclophosphamide (CP)-induced hemorrhagic cystitis and nephrotoxicity in rats. For this purpose, experimental rats were divided into 6 groups; control (Group 1), 150 mg/kg CP (Group 2), 5 mg/kg kefir (Group 3), l0 mg/kg kefir (Group 4), 5 mg/kg kefir+150 CP (Group 5), l0 mg/kg kefir+150 CP (Group 6). Since there was no difference in kefirs fermented on different days, kefirs from the 1st, 2nd, and 3rd days were mixed and given to the rats for 12 days, while CP was given as an only dose and i.p. on the 12th day of the experiment. Histologic evaluations revealed that CP caused toxicity in kidney and bladder. On the other hand, biochemical evaluations showed a significant increase in serum blood urea nitrogen (BUN) and creatinine (Cre) levels, which are tissue toxicity markers, and a significant decrease in catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, which are intracellular antioxidant system markers, in the CP-treated experimental group. However, all values were reversed as a result of kefir (5 and 10 mg/kg) treatment. These results showed that kefir is an effective protective agent against CP-induced hemorrhagic cystitis and nephrotoxicity.

Etik Beyan

This study was approved by Ethics Committee of Eskisehir Osmangazi University Animal Experiments Local Ethics Committee (784-145 / 2020).

Destekleyen Kurum

This experimental research was financed by Mardin Artuklu University / Coordination Unit of Scientific Research Project (MAU.BAP.20. SHMYO.004).

Kaynakça

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Probiyotik Kefirin Sıçanlarda Siklofosfamid Kaynaklı Nefrotoksisite ve Ürotoksisite Üzerine İmmünoterapötik ve Hücre Koruyucu Etkileri

Yıl 2024, Cilt: 24 Sayı: 06, 1275 - 1284

Öz

Doğal olarak oluşan fermente bir süt ürünü olan kefirin, sıçanlarda siklofosfamid (CP) ile indüklenen hemorajik sistit ve nefrotoksisiteye karşı antioksidan, anti-apoptotik ve anti-inflamatuar etkileri gibi farmakolojik ve terapötik niteliklerini değerlendirmek. Bu amaçla, deneysel sıçanlar 6 gruba ayrılmıştır; control (Grup 1), 150 mg/kg CP (Grup 2), 5 mg/kg kefir (Grup 3), l0 mg/kg kefir (Grup 4), 5 mg/kg kefir+150 CP (Grup 5), l0 mg/kg kefir+150 CP (Grup 6). Farklı günlerde fermente edilen kefirlerde farklılık olmadığı için 1., 2. ve 3. gün kefirleri karıştırılarak sıçanlara 12 gün boyunca verilmiş, CP ise deneyin 12. gününde tek doz ve i.p. olarak verilmiştir. Daha sonra elde edilen parametreler değerlendirilmiştir. Histolojik değerledirmeler sonucunda CP'nin böbrek ve mesane de toksisiteye neden olduğu belirlenmiştir. Öte yandan biyokimyasal değerlendirme ile CP uygulanan deney grubunda, doku toksisite belirteçleri olan serum kan üre nitrojen (BUN) ve kreatinin (Cre) seviyelerindeki önemli artış görülğrken hücre içi antioksidan sistem belirteçlerinden olan katalaz (CAT), glutatyon (GSH), superoksit dismutaz (SOD) ve glutatyon peroksidaz (GPx) düzeylerinde ise önemli azalma olduğu belirlenmiştir. Bununla birlikte, kefir (5 ve 10 mg/kg) tedavisi neticesinde meydana gelen tüm değerler tersine dönmüştür. Bu sonuçlar kefirin CP kaynaklı hemorajik sistit ve nefrotoksisiteye karşı etkili bir koruyucu olduğunu göstermiştir.

Etik Beyan

Bu çalışma Eskişehir Osmangazi Üniversitesi Hayvan Deneyleri Yerel Etik Kurulu tarafından onaylanmıştır (784-145/2020).

Destekleyen Kurum

Bu deneysel araştırma Mardin Artuklu Üniversitesi / Bilimsel Araştırma Projeleri Koordinasyon Birimi (MAU.BAP.20. SHMYO.004) tarafından finanse edilmiştir.

Kaynakça

  • Aboulhoda, B.E., Amin, S.N., Thomann, C., Youakim, M., and Hassan, S.S., 2020. Effect of thymoquinone on cyclophosphamide-induced injury in the rat urinary bladder. Archives of Medical Science, 16, 1-12 https://doi.org/10.5114/aoms.2020.97061
  • Abraham, P. and Isaac, B., 2011. The effects of oral glutamine on cyclophosphamide-induced nephrotoxicity in rats. Human & experimental toxicology, 30, 616-623. https://doi.org/10.1177/0960327110376552
  • Akbaş, N., Suleyman, B., Mammadov, R., Yazıcı, G. N., Bulut, S., Süleyman, H., 2022. Effect of taxifolin on cyclophosphamide-induced oxidative and inflammatory bladder injury in rats. Experimental Animals, 71 (4), 460-467. https://doi.org/10.1538/expanim.22-0030
  • Aladaileh, S.H., Hussein, O.E., Abukhalil, M.H., Saghir, S.A., Bin-Jumah, M., Alfwuaires, M. A., Mahmoud, A.M., 2019. Formononetin upregulates Nrf2/HO-1 signaling and prevents oxidative stress, inflammation, and kidney injury in methotrexate-induced rats. Antioxidants, 8 (10), 430. https://doi.org/10.3390/antiox8100430
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  • Güven, A., Güven, A. and Gülmez, M., 2003. The effect of kefir on the activities of gsh-px, gst, cat, gsh and lpo levels in carbon tetrachloride-induced mice tissues. Journal of Veterinary Medicine, Series B, 50(8), 412-416. https://doi.org/10.1046/j.1439-0450.2003.00693.x
  • Hadisaputro, S., 2011. Effects of oral clear kefir probiotics on glycemic status, lipid peroxidation, antioxidative properties of streptozotocin induced hyperglycemia wistar rats. Gizi Indonesia, 34(1). Hadisaputro, S., Djokomoeljanto, R. and Soesatyo, M., 2012. The effects of oral plain kefir supplementation on proinflammatory cytokine properties of the hyperglycemia wistar rats induced by streptozotocin. Acta Medica Indonesiana, 44(2), 100-104. Haghi-Aminjan, H., Asghari, M.H., Farhood, B., Rahimifard, M., Hashemi Goradel, N., Abdollahi, M., 2018. The role of melatonin on chemotherapy-induced reproductive toxicity. Journal of Pharmacy Pharmacology, 70(3), 291-306. https://doi.org/10.1111/jphp.12855
  • Ijaz, M.U., Mustafa, S., Batool, R., Naz, H., Ahmed, H., and Anwar, H., 2022. Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction. Human & Experimental Toxicology, 41, 09603271221132140. https://doi.org/10.1177/09603271221132140
  • Jiang, S., Zhang, Z., Huang, F., Yang, Z., Yu, F., Tang, Y., Ding, G., 2020. Protective effect of low molecular weight peptides from solenocera crassicornis head against cyclophosphamide-induced nephrotoxicity in mice via the keap1/nrf2 pathway. Antioxidants, 9(8), 745. https://doi.org/10.3390/antiox9080745
  • Jiang, X., Ren, Z., Zhao, B., Zhou, S., Ying, X., Tang, Y., (-2020). Ameliorating effect of pentadecapeptide derived from cyclina sinensis on cyclophosphamide-induced nephrotoxicity. Marine Drugs, 18(9), 462. https://doi.org/10.3390/md18090462
  • Kahraman, M., Ertekin, Y.H. and Satman, İ., 2021. The effects of kefir on kidney tissues and functions in diabetic rats. Probiotics and Antimicrobial Proteins, 13(2), 375-382. https://doi.org/10.1007/s12602-020-09698-9
  • Knights, K.M., Rowland, A. and Miners, J.O., 2013. Renal drug metabolism in humans: The potential for drug–endobiotic interactions involving cytochrome p450 (cyp) and udp-glucuronosyltransferase (ugt). British Journal of Clinical Pharmacology, 76(4), 587-602. https://doi.org/10.1111/bcp.12086
  • Kojima, N., Slaughter, T.N., Paige, A., Kato, S., Roman, R. J., Williams, J.M., 2013. Comparison of the development diabetic induced renal disease in strains of goto-kakizaki rats. Journal of diabetes & metabolism, Suppl 9(5): S9-005. https://doi.org/10.4172/2155-6156.S9-005
  • Lin, X., Yang, F., Huang, J., Jiang, S., Tang, Y., Li, J., 2020. Ameliorate effect of pyrroloquinoline quinone against cyclophosphamide-induced nephrotoxicity by activating the Nrf2 pathway and inhibiting the nlrp3 pathway. Life Sciences, 256, 117901. https://doi.org/10.1016/j.lfs.2020.117901
  • Mahmoud, A.M., Germoush, M.O., Alotaibi, M.F., Hussein, O.E., 2017. Possible involvement of nrf2 and pparγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity. Biomedicine & Pharmacotherapy, 86, 297-306. https://doi.org/10.1016/j.biopha.2016.12.047
  • Manesh, C. and Kuttan, G., 2005. Effect of naturally occurring isothiocyanates in the inhibition of cyclophosphamide-induced urotoxicity. Phytomedicine, 12(6), 487-493. https://doi.org/10.1016/j.phymed.2003.04.005
  • Marshall, V.M. and Cole, W.M., 1985. Methods for making kefir and fermented milks based on kefir. Journal of Dairy Research, 52(3), 451-456. https://doi.org/10.1017/S0022029900024353
  • McDermott, E.M. and Powell, R.J., 1996. Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide. Annals of the Rheumatic Diseases, 55(4), 224. https://doi.org/10.1136/ard.55.4.224
  • Mills, K.A., Chess-Williams, R. and McDermott, C., 2019. Novel insights into the mechanism of cyclophosphamide-induced bladder toxicity: Chloroacetaldehyde’s contribution to urothelial dysfunction in vitro. Archives of Toxicology, 93(11), 3291-3303. https://doi.org/10.1007/s00204-019-02589-1
  • Mythili, Y., Sudharsan, P.T., Selvakumar, E., Varalakshmi, P., 2004. Protective effect of dl-α-lipoic acid on cyclophosphamide induced oxidative cardiac injury. Chemico-Biological Interactions, 151(1), 13-19. https://doi.org/10.1016/j.cbi.2004.10.004
  • Peng, X., Zhang, X., Wang, C., Olatunji, O.J., 2022. Protective effects of asperuloside against cyclophosphamide-induced urotoxicity and hematotoxicity in rats. Open Chemistry, 20(1), 1444-1450. https://doi.org/10.1515/chem-2022-0234
  • Pugliero, S., Lima, D.Y., Rodrigues, A.M., Bogsan, C.S.B., Rogero, M.M., Punaro, G.R., Higa, E.M.S., 2021. Kefir reduces nitrosative stress and upregulates nrf2 in the kidney of diabetic rats. International Dairy Journal, 114, 104909. https://doi.org/10.1016/j.idairyj.2020.104909
  • Punaro, G.R., Maciel, F.R., Rodrigues, A.M., Rogero, M.M., Bogsan, C.S.B., Oliveira, M.N., Higa, E.M.S., 2014. Kefir administration reduced progression of renal injury in stz-diabetic rats by lowering oxidative stress. Nitric Oxide, 37, 53-60. https://doi.org/10.1016/j.niox.2013.12.012
  • Qiu, H., Li, J., Huang, Y., Shen, C., Dai, L., Su, Q., Li, W., 2023. Sulfhydryl functionalized hyaluronic acid hydrogels attenuate cyclophosphamide-induced bladder injury. Biomedical Materials, 18(1), 015026. https://doi.org/10.1088/1748-605X/acadc2
  • Rehman, M.U., Tahir, M., Ali, F., Qamar, W., Lateef, A., Khan, R., Sultana, S., 2012. Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of swiss albino mice: The protective effect of ellagic acid. Molecular and Cellular Biochemistry, 365(1), 119-127. https://doi.org/10.1007/s11010-012-1250-x
  • Sedlak, J. and Lindsay, R.H., 1968. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with ellman's reagent. Analytical biochemistry, 25, 192-205. Sinanoglu, O., Yener, A.N., Ekici, S., Midi, A., Aksungar, F. B., 2012. The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats. Urology, 80(6), 1392.e1391-1392.e1396. https://doi.org/10.1016/j.urology.2012.06.053
  • Sugumar, E., Kanakasabapathy, I. and Abraham, P., 2007. Normal plasma creatinine level despite histological evidence of damage and increased oxidative stress in the kidneys of cyclophosphamide treated rats. Clinica chimica acta; international journal of clinical chemistry, 376(1-2), 244-245. https://doi.org/10.1016/j.cca.2006.04.006
  • Sun, Y., Oberley, L.W. and Li, Y., 1988. A simple method for clinical assay of superoxide dismutase. Clinical chemistry, 34(3), 497-500. Temel, Y., Kucukler, S., Yıldırım, S., Caglayan, C., Kandemir, F.M., 2020. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. Naunyn-Schmiedeberg's Archives of Pharmacology, 393(3), 325-337. https://doi.org/10.1007/s00210-019-01741-z
  • Toba, T., 1987. Comparative study of polysaccharides from kefir grains, an encapsulated homofermentative lactobacillus species and lactobacillus kefir. Milchwissenschaften, 42, 565-568. Urdaneta, E., Barrenetxe, J., Aranguren, P., Irigoyen, A., Marzo, F., Ibáñez, F.C., 2007. Intestinal beneficial effects of kefir-supplemented diet in rats. Nutrition Research, 27(10), 653-658. https://doi.org/10.1016/j.nutres.2007.08.002
  • Usoh, I., Akpan, E., Etim, E., Farombi, E., 2005. Antioxidant actions of dried flower extracts of hibiscus sabdariffa l. On sodium arsenite-induced oxidative stress in rats. Pakistan journal of Nutrition, 4(3), 135-141. Valibeik, A., Naderi, N., Amini, A., Dastjerd, N.T., Monfared, S.R., Jafaripour, L., Ahmadvand, H., 2020. Effect of camphor on biochemical factors and gene expression of antioxidant enzymes, inflammatory and apoptotic factors against gentamicin-induced nephrotoxicity in rats. Journal of Renal Injury Prevention, 10(3), e21-e21. https://doi.org/10.34172/jrip.2021.21
  • Wróbel, A., Serefko, A., Bańczerowska-Górska, M., Szopa, A., Dudka, J., Poleszak, E., 2019. Intravesical administration of blebbistatin prevents cyclophosphamide-induced toxicity of the urinary bladder in female wistar rats. Neurourology and urodynamics, 38(4), 1044-1052. https://doi.org/10.1002/nau.23973
  • Yener, A., Sehitoglu, M., Ozkan, M., Bekler, A., Ekin, A., Cokkalender, O., Ozcan, S., 2015. Effects of kefir on ischemia-reperfusion injury. European Review for Medical Pharmacological Sciences, 19(5), 887-896. Yıldız, S.C. 2020. Properties and health benefits of probiotic and prebiotic kefir. Academic Studies in Science Mathematics-II, 59. Yildiz, S.Ç. and Gözüoğlu, G., 2021. Myeloprotective and hematoprotective role of kefir on cyclophosphamide toxicity in rats. Archives of Clinical Experimental Medicine, 6(2), 77-82. https://doi.org/10.25000/acem.903843
  • Zanger, U. and Klein, K., 2013. Pharmacogenetics of cytochrome p450 2b6 (cyp2b6): Advances on polymorphisms, mechanisms, and clinical relevance. Frontiers in genetics, 4 (24). https://doi.org/10.3389/fgene.2013.00024
Toplam 57 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hayvan Bilimi (Diğer)
Bölüm Makaleler
Yazarlar

Songül Çetik-yıldız 0000-0002-7855-5343

Cemil Demir 0000-0002-6365-0196

Mustafa Cengiz 0000-0002-6925-8371

Halit Irmak 0000-0002-8184-9377

Betül Peker Cengiz 0000-0002-2503-7446

Adnan Ayhancı 0000-0003-4866-9814

Erken Görünüm Tarihi 11 Kasım 2024
Yayımlanma Tarihi
Gönderilme Tarihi 23 Ocak 2024
Kabul Tarihi 11 Ağustos 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 24 Sayı: 06

Kaynak Göster

APA Çetik-yıldız, S., Demir, C., Cengiz, M., Irmak, H., vd. (2024). Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 24(06), 1275-1284.
AMA Çetik-yıldız S, Demir C, Cengiz M, Irmak H, Peker Cengiz B, Ayhancı A. Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. Kasım 2024;24(06):1275-1284.
Chicago Çetik-yıldız, Songül, Cemil Demir, Mustafa Cengiz, Halit Irmak, Betül Peker Cengiz, ve Adnan Ayhancı. “Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 24, sy. 06 (Kasım 2024): 1275-84.
EndNote Çetik-yıldız S, Demir C, Cengiz M, Irmak H, Peker Cengiz B, Ayhancı A (01 Kasım 2024) Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 24 06 1275–1284.
IEEE S. Çetik-yıldız, C. Demir, M. Cengiz, H. Irmak, B. Peker Cengiz, ve A. Ayhancı, “Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 24, sy. 06, ss. 1275–1284, 2024.
ISNAD Çetik-yıldız, Songül vd. “Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 24/06 (Kasım 2024), 1275-1284.
JAMA Çetik-yıldız S, Demir C, Cengiz M, Irmak H, Peker Cengiz B, Ayhancı A. Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2024;24:1275–1284.
MLA Çetik-yıldız, Songül vd. “Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 24, sy. 06, 2024, ss. 1275-84.
Vancouver Çetik-yıldız S, Demir C, Cengiz M, Irmak H, Peker Cengiz B, Ayhancı A. Immunotherapeutic and Cell-Protective Effects of Probiotic Kefir on Cyclophosphamide‐induced Nephrotoxicity and Urotoxicity in Rats. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2024;24(06):1275-84.