Kefirin sıçanlarda siklofosfamid-nedenli oksidatif stres ve akciğer hasarı üzerine antioksidan ve koruyucu etkilerinin in vitro olarak değerlendirilmesi

Year 2024, Volume: 5 Issue: 1, 11 - 18, 30.04.2024

Songül Çetik Yıldız Cemil Demir Mustafa Cengiz Betül Peker Cengiz Adnan Ayhancı

https://doi.org/10.58605/bingolsaglik.1436057

Abstract

Amaç: Doğal bir probiyotik olan kefir, antioksidatif ve antitümör özelliklerinin yanı sıra mikrobiyal türler ve fermantasyondan kaynaklanan yararlı özelliklere de sahiptir. Siklofosfamid (SF), kanser tedavisinde oldukça tercih edilen ancak hem humoral hem de hücresel bağışıklığı baskılayabilen sitotoksik bir ilaçtır. SF'nin immünsüpresif etkisinin olması ve akciğer gibi çoklu organ toksisitesine neden olması nedeniyle etkili yüksek dozda kullanımı sınırlıdır.
Yöntem: Wistar albino sıçanlar 6 gruba ayrıldı. Kontrol, 150 mg/kg SF, 5 mg/kg kefir, 5 mg/kg kefir +150 SF, 10 mg/kg kefir, 10 mg/kg kefir+150 SF. Ratlara 1., 2. ve 3. günlerdeki fermente kefirler karıştırılarak 12 gün süreyle verilirken, deneyin 12. gününde SF tek doz ve i.p. olarak verildi. Alınan kan ve doku parametreleri değerlendirildi.
Bulgular: Oksidatif stresi gösteren OSI değerinin SF uygulanan grupta arttığı, SF+kefir gruplarında ise bu düzeyin kontrole yaklaştığı görüldü. Ayrıca SF uygulanan sıçanların akciğer parankiminde dejenerasyon, interalveoler bölgede yoğun inflamasyon, alveollerde kollaps ve bronşiyol çevresinde yoğun inflamasyon gözlenirken, kefir verilen gruplarda bu etkilerin etkin bir şekilde düzeldiği gözlendi.
Sonuç: Sonuç olarak deneysel çalışmamızda kefirin SF kaynaklı oksidatif stres, konjesyon, alveolar hasar ve inflamasyon üzerinde antioksidatif ve koruyucu etkiler gösterdiği gözlendi.

Keywords

Kefir, siklofosfamid, antioksidan, oksidatif stres, akciğer hasarı, sıçan

Ethical Statement

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

Supporting Institution

This study was financed by Mardin Artuklu Univ. BAP Coordination Office (MAU.BAP.20.SHMYO.004).

Project Number

MAU.BAP.20.SHMYO.004

Evaluation of in vitro antioxidative and protective effects of kefir on cyclophosphamide-upon oxidative stress and lung damage in rats

Abstract

Purpose: Kefir, a natural probiotic, has antioxidative and antitumor properties, as well as potential beneficial properties resulting from microbial species and fermentation. Cyclophosphamide (CYP) is a cytotoxic drug that is highly preferred in cancer therapy but can suppress both humoral and cellular immunity. The use of effective doses is limited because CYP has an immunosuppressive effect and causes multiple organ toxicity such as the lungs, and the use of effective high doses is restricted.
Methods: Wistar albino rats were divided into 6 groups. As; control, 150 mg/kg CYP, 5 mg/kg kefir, 5 mg/kg kefir +150 CYP, l0 mg/kg kefir, l0 mg/kg kefir+150 CYP. Fermented kefirs from the 1st, 2nd and 3rd days were mixed and given to the rats for 12 days, while CYP was given as a single dose and ip on the 12th day of the experiment. The received parameters were evaluated.
Results: It was observed that the OSI value, which indicates oxidative stress, increased in the CYP-administered group, and this level approached control in the CYP+kefir groups. In addition, while degeneration, intense inflammation in the interalveolar area, collapse of the alveoli, and intense inflammation around the bronchioles were observed in the lung parenchyma of CYP-administered rats, it was observed that these effects were effectively improved in the groups given kefir+CYP.
Conclusion: In conclusion, in our study, it was observed that kefir showed antioxidative and protective effects on CYP-induced oxidative stress, congestion, alveolar damage and inflammation.

Keywords

Kefir, cyclophosphamide, antioxidant, oxidative stress, lung damage, rats

Project Number

MAU.BAP.20.SHMYO.004

References

• Akalin AS, Tokusoglu O. A Potential Anticarcinogenic Agent: Conjugated Linoleic Acid. Pakistan J Nutr 2003;2:109-110.
• Sarica E. Production, characteristics, and alcohol content of kefir. J Halal & Ethical Res 2022;4(2):69-82.
• 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;8:412-423.
• Rosa DD, Dias MS, Grześkowiak LM, Milk Kefir. Nutr Res Rev. 2017;30(1):82-96.
• Ahmed Z, Wang Y, Ahmad A, et al. Kefir and health: a contemporary perspective. Crit Rev Food Sci Nutr 2013;53:422-434.
• 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.
• Akbay GD. Anticarcinogenic Role of Kefir. Cumhuriyet Üniv. Sağ Bil Enst Derg 2020;(5)2:73-82.
• 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 H. triquetrifolium seed extract against CY-induced toxicity. Braz Arch Biol Technol 2019b;62(4).
• Roy P, Waxman DJ. Activation of oxazaphosphorines by cytochrome P450: application to gene-directed enzyme prodrug therapy for cancer. Toxicol in Vitro 2006;20:176-186
• 1Kern JC, Kehrer JP. Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chem Biol Interact 2002;139(1):79-95
• 1MacAllister 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):259-266.
• 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):13-19.
• Marshall V. Observations on the structure of kefir grains and the distribution of the microflora. J Appl Bacteriol 1984;57:491-497.
• Cooper JAD, Jr While DA, Matthay RA, et al. Drug-induced pulmonary disease. Am Rev Respir Dis 1986;133:321-340.
• Matsuu M, Shichijo K, Okaichi K, et al. The protective effect of fermented milk kefir on radiation-induced apoptosis in colonic crypt cells of rats. J Dairy Res 2003;44:111-115
• Mohamed MT, Zaitone SA, Ahmed A, Mehanna ET, El-Sayed NM. Raspberry ketones attenuate cyclophosphamide-induced pulmonary toxicity in mice through inhibition of oxidative stress and NF-ΚB pathway. Antioxidants 2020;9:1168.
• Naraoka T, Sumi T, Keira Y, Nakata H, Chiba H. Epirubicin and Cyclophosphamide-induced acute fibrinous and organizing pneumonia. Am J Respir Crit Care Med 2021;204:92-93.
• Abd El‐Ghafar OA, Hassanein EH, Sayed AM, Rashwan EK, Shalkami AGS, Mahmoud AM. Acetovanillone prevents cyclophosphamide‐induced acute lung injury by modulating PI3K/Akt/mTOR and Nrf2 signaling in rats. Phytother Res 2021;35:4499-4510.
• 1Guven 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):412-416.
• Liu, JR, Chen MJ, Lin CW. Antimutagenic and antioxidant properties of milk-kefir and soymilk-kefir. J Agric Food Chem 2005;53:2467-2474.
• Tomar O, Caglar A, Akarca G. Kefir and its importance for health. AKU J Sci 2017;17(2):834-853.
• 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):341-349.
• Arslan S. A review: Chemical, microbiological and nutritional characteristics of kefir. CyTA-J Food 2015;13:340-345.
• Rosa DD, Dias MS, Grześkowiak LM, Reis SA, Conceiçao LL, Peluzio MCG. Milk Kefir. Nutr Res Rev 2017;30(1):82-96.
• Gozuoglu G, Yıldız SC. Myeloprotective and hematoprotective role of kefir on cyclophosphamide toxicity in rats. Arch Clin Exp Med 2021;6(2):77-82.
• Gould VE, Miller J. Sclerosing alveolilis induced by cyclophosphamide. Am J Pathol 1975;81:513-520.
• Sengul E, Gelen V, Gedikli S, Ozkanlar S, Gur C, Celebi F, Cınar A. The protective effect of quercetin on cyclophosphamide-induced lung toxicity in rats. Biomed Pharmacother 2017;92:303-307
• Yazici GN. Kemoterapi uygulamasının sıçan akciğer dokusuna etkilerinin yapısal düzeyde incelenmesi. Gazi Üniv Sağlık Bil Enst. Histoloji ve Embriyoloji Anabilim Dalı. Yükseklisans Tezi, 2009.
• Pouzet MT, Travis EL. No change in repair capacity of mouse lung irradiated three mounths after a single dose of cyclophosphamide. Cancer Res. 1992;52:1096-100.
• Akbay GD. Kefirin Antikanserojenik Rolü. Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Derg 2020;5(2):73-82
• 3Guzel-Seydim ZB, Seydim AC, Greene AK. Comparison of amino acid profiles of milk, yogurt and Turkish kefir. Milchwissenschaft 2003;58(3-4):158-160.
• Furukawa N, Matsuoka A, Takahashi T,Yamanaka Y. Anti-metastatic effect of Kefir grain components on Lewis lung carcinoma and highly metastatic B16 melanoma in mice. J Agric Sci 2000;45:62-70.
• Cevikbas A, Yemni E, Ezzedenn FW, Yardimici T. Antitumoural antibacterial and antifungal activities of kefir and kefir grain. Phytother Res 1994;8:78-82
• Yildiz SC. Current immunotherapeutic approaches in cancer immunotherapy. Taser F, Editor. Advances in Basic Medical Sciences. Platanus Publishing; 2023:25-39.