Ratlarda Siklofosfamid ile İndüklenen Oral Mukozitte Lokal Olarak Uygulanan Karanfil ve Yeşil Çay Hidrosollerinin Etkileri

Abstract

Bu araştırmada, ratlarda siklofosfamid ile oluşturulan oral mukozit modelinde lokal uygulanan karanfil ve yeşil çay hidrosolünün etkisi araştırılmıştır. Bu çalışma, preklinik, in vivo deneysel ve analitik bir araştırmadır. Çalışma, 40 dişi Wistar albino rat kullanılarak yürütülmüş ve ratlar rastgele 8 gruba ayrılmıştır. Mukozit indüksiyonu için ratlara intraperitoneal olarak tek yüksek dozda (300 mg/kg) siklofosfamid uygulanmıştır. Mukozit bakımını sağlamak için deney gruplarındaki ratlara günde iki kez karanfil veya yeşil çay hidrosolü ağız spreyi şeklinde uygulanmıştır. Bu uygulamalara kalp kanı ve sağ yanak mukozasından doku örneklerinin alındığı deneyin 4. gün ve 8. gününe kadar devam edilmiştir. Toplanan kan örneklerinden serum toplam antioksidan seviyesi (TAS) ve toplam oksidan seviyesi (TOS) ölçülmüş, doku örnekleri ise erozyon, fibrozis ve inflamatuar hücre infiltrasyonu açısından incelenmiştir. Karanfil ve yeşil çay hidrosolü uygulanan gruplarda serum TAS ortalama değeri daha yüksek, TOS değeri ise daha düşüktü. Ayrıca pozitif kontrol gruplarına kıyasla, karanfil ve yeşil çay hidrosolü uygulanan gruplarda erozyon istatistiksel olarak anlamlı derecede (P=0,003) daha az gelişti. Sekizinci gün karanfil ve yeşil çay hidrosolü gruplarında fibrozis daha az ve inflamatuar hücre infiltrasyonu minimum seviyedeydi. Ratlarda, siklofosfamide bağlı gelişen oral mukozitte karanfil ve yeşil çay hidrosolünün erozyonu önlemede etkili olduğu saptanmıştır. Karanfil ve yeşil çay hidrosolünün hastalarda oral mukoziti önlemeye yönelik etkisinin çalışmalarla araştırılması önerilmektedir.

Keywords

• Karanfil
• Oral mukozit
• Siklofosfamid
• Yeşil çay
• Kanser

Effects of Locally Applied Clove and Green Tea Hydrosols on Cyclophosphamide-Induced Oral Mucositis in Rats

Abstract

This study investigated the effect of clove and green tea hydrosol applied locally in a rat model of oral mucositis induced with cyclophosphamide. This study is a preclinical, in vivo, experimental, and analytical study. The study was conducted using 40 female Wistar albino rats and were randomly divided into 8 groups. A single high-dose cyclophosphamide injection was administered intraperitoneally for mucositis induction. For mucositis care, the rats received twice daily oral spray clove or green tea hydrosol in the experimental groups. These interventions continued until collection of cardiac blood samples and oral mucosal tissue samples from the right cheek on day 4 or day 8. Serum total antioxidant status (TAS) and total oxidant status (TOS) were determined from the blood samples, and the tissue samples were analyzed for erosion, fibrosis, and inflammatory cell infiltration. Mean serum TAS was higher and TOS was lower in the clove and green tea hydrosol groups. There was also significantly less erosion in the clove and green tea hydrosol groups than in the positive control groups (P=0.003). On day 8, the clove and green tea hydrosol groups had less fibrosis and showed minimal inflammatory cell infiltration. In rats, clove and green tea hydrosols were found to be effective in preventing erosion associated with cyclophosphamide-induced oral mucositis. It is recommended that studies be conducted to investigate the effect of clove and green tea hydrosols on preventing oral mucositis in patients.

Keywords

• Clove
• Cyclophosphamide
• Green tea
• Oral mucositis
• Cancer

References

1. Almeida, S.B.D., Monteiro, M.C.S.A., Lima, A.V.P.D., Menezes, D.B.D., & Monteiro, S.M.N. (2014). Protective effect of Camellia sinensis on methotrexate-induced small intestinal mucositis in mice. Food and Nutrition Sciences, 5, 443-448. https://doi.org/10.4236/fns.2014.55052
2. Al-Refai, A.S., Ali, A.B.H., & Kamal, K.A. (2014). Immunohistochemical Study of the Effect of Green Tea Extract on Methotrexate-Induced Oral Mucositis in Albino Rats. Journal of Cytology & Histology, 5(3), 1-7. https://doi.org/10.4172/2157-7099.1000227
3. Al-Refai, A.S. (2017). Chemoprotective effect of ascorbic acid on cyclophosphomide induced oral toxicity. Zanco Journal of Medical Sciences, 21(1), 1540-1551. https://doi.org/10.15218/zjms.2017.002
4. Aykaç, G., Uzun, M.B., & Özçelikay, G. (2014). Tea in Social Aspect “Camellia Sinensis”. Lokman Hekim Journal, 4(1), 1-5
5. Babic, A., & Murray, J. (2019). Role of Nursing in HSCT. E. Carreras, C. Dufour, M. Mohty, & N. Kröger (Eds). In: The EBMT Handbook Hematopoietic Stem Cell Transplantation and Cellular Therapies, Switzerland, Springer Nature, 237-243. https://doi.org/10.1007/978-3-030-02278-5
6. Baharvand, M., Jafari, S., & Mortazavi, H. (2017). Herbs in Oral Mucositis. Journal of Clinical and Diagnostic Research, 11(3), 5-11. https://doi.org/10.7860/JCDR/2017/21703.9467
7. Baysal, E., & Sarı, D. (2016). Current approaches in oral mucositis prevention, care and treatment in hematopoietic stem cell transplantation: Literature review. Journal of Human Sciences, 13(3), 5721-5739. https://doi.org/10.14687/jhs.v13i3.4036
8. Carulli, G., Rocco, M., Panichi, A., Chios, C.F., Ciurli, E., Mannucci, C., et al. (2013). Treatment of Oral Mucositis in Hematologic Patients Undergoing Autologous or Allogeneic Transplantation of Peripheral Blood Stem Cells: A Prospective, Randomized Study With a Mouthwash Containing Camelia Sinensis Leaf Extract. Hematology Reports, 5(1), e6. https://doi.org/10.4081/hr.2013.e6

9. Cidon, E.U. (2018). Chemotherapy induced oral mucositis: prevention is possible. Chinese Clinical Oncology, 7(1), 6. https://doi.org/10.21037/cco.2017.10.01
10. Çıtlak, K., & Kapucu, S. (2015). Current Approaches to Oral Mucositis Prevention and Treatment In Patients Receiving Chemotherapy: Evidence-Based Practices, Journal of Hacettepe University Faculty of Nursing, 70-77
11. Danthu, P., Simanjuntak, R., Fawbush, F., Tsy, J.L., Razaβimamonjison, G., Abdillahi, M.M., et al. (2020). The clove tree and its products (clove bud, clove oil, eugenol): prosperous today but what of tomorrow’s restrictions?. World, 61(58,172), 52-915. https://doi.org/10.17660/th2020/75.5.5
12. Erel, O. (2005). A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry, 38, 1103-1111. https://doi.org/10.1016/j.clinbiochem.2005.08.008
13. Erel, O. (2004). A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical Biochemistry, 37, 277-285. https://doi.org/10.1016/j.clinbiochem.2003.11.015
14. Ghorbani, A., Sadrzadeh, A., Habibi, E., Dadgar, K., Akbari, J., Moosazadeh, M., et al. (2018). Efficacy of Camellia sinensis extract against Candida species in patients with denture stomatitis. Medical Mycology, 4(3), 15. https://doi.org/10.18502/cmm.4.3.174 Giacomelli, I., Scartoni, D., Fiammetta, M., Baki, M., Zei, G., Muntoni,
15. C., et al. (2015). Oral lapacho-based medication: an easy, safe, and feasible support to prevent and/or reduce oral mucositis during radiotherapy for head and neck cancer. Nutrition and cancer, 67(8), 1249-1254. https://doi.org/10.1080/01635581.2015.1082114
16. Göktuna, G. (2017). Investigation of the frequency and risk factors of oral mucositis development in patients receiving chemotherapy. [Master’s Thesis Izmir Dokuz Eylul University]
17. Hepokur, C. Investigation of Cytotoxic Effects of Eugenia Caryophyllus (Clove). (2018). Cumhuriyet Dental Journal, 21(3), 173-177. https://doi.org/10.7126/cumudj.444426 İzgü, N. (2017). Complementary Therapies in the Management of Induced Oral Mucositis during Cancer Treatment, Journal of Education and Research in Nursing, 14(4), 304-310. https://doi.org/10.5222/HEAD.2017.304
18. Kaynar, L. (2010). The Effect of Royal Jelly on Methotrexate-Induced Mucositis and Oxidative Stress in Rats. [Subspecialty Thesis, Erciyes University] https://tez.yok.gov.tr/UlusalTezMerkezi/tezDetay. jsp?id=y7foSS3jHkgqRXXOTNubaw&no=iTRHHnx5yeWIJnYeJn9T2w
19. Kong, M., Hwang, D.S., Yoon, S.W., Kim, J. (2016). The effect of clove- based herbal mouthwash on radiation-induced oral mucositis in patients with head and neck cancer: A single-blind randomized preliminary study. Oncotargets and Therapy, 9, 4533-4538
20. Lalla, R.V., Solé, S., Becerra, S., Carvajal, C., Bettoli, P., Letelier, H., et al. (2020). Efficacy and safety of Dentoxol® in the prevention of radiation-induced oral mucositis in head and neck cancer patients (ESDOM): a randomized, multicenter, double-blind, placebo- controlled, phase II trial. Supportive Care in Cancer, 28, 5871-5879. https://doi.org/10.1007/s00520-020-05358-4
21. Magalhães, C.B., Riva, D.R., DePaula, L.J., Brando-Lima, A., Koatz, V.L.G., Leal-Cardoso J.H., et al. (2010). In vivo anti- inflammatory action of eugenol on lipopolysaccharide-induced lung injury. Journal of Applied Physiology, 108(4), 845-851. https://doi.org/10.1152/japplphysiol.00560.2009
22. Milind, P., Deepa, K. (2011). Clove: A Champion Spice. International Journal of Research in Ayurveda & Pharmacy, 2(1), 47-54
23. Mutluay Yayla, E., İzgü, N., Özdemir, L., Aslan Erdem, S., Kartal, M. (2016). Sage tea-thyme-peppermint hydrosol oral rinse reduces chemotherapy-induced oral mucositis: A randomized controlled pilot study. Complementary Therapies in Medicine, 27, 58-64. https://doi.org/10.1016/j.ctim.2016.05.010
24. Mutluay Yayla, E. (2017). Evidence-Based Practices for Mucositis. Journal of Education and Research in Nursing, 14(3), 223-227. https://doi.org/10.5222/HEAD.2017.223
25. Negrin, R. S., & Treister, N. S. (2024). Oral toxicity associated with systemic anticancer therapy. UpToDate, 17 (9). https://www. uptodate.com/contents/oral-toxicity-associated-with-systemic- anticancer-therapy
26. Oğuz, Y., Diker, N., Gülsever, S., Yılmaz Akçay, E. (2023). Effects of Hyaluronic Acid Gel Application on Incisional Oral Mucosal Wound Healing: An Experimental Study, Turkiye Klinikleri Journal of Dental Sciences, 29(2), 225-33
27. Oronsky, B., Goyal, S., Kim, M.M., Cabrales, P., Lybeck, M., Caroen, S., et al. (2018). 11A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis, Translational Oncology, (3), 771-778. https://doi.org/10.1016/j.tranon.2018.03.014
28. Özsoy, S., Yıldırım, J.G. (2012). Animal Research in Nursing. Journal of Research and Development in Nursing, 1, 56–69
29. Razmara, F., Khayamzadeh, M. (2019). An Investigation into the Prevalence and Treatment of Oral Mucositis After Cancer Treatment. International Journal of Cancer Management, 12(11), e88405. https://doi.org/10.5812/ijcm.88405Rodríguez, O., Sánchez, R., Verde, M., Núñez, M., Ríos, R., Chávez, A. (2014). Obtaining the essential oil of Syzygium aromaticum, identification of eugenol and its effect on Streptococcus mutans. Journal of Oral Research, 3(4), 218-224
30. Saleh, A.O., Khleel, A.K., Almahana, J. (2019). Simulation Assessment of the Protective Role of Vitamin C and E against Cytotoxic Effects of Cyclophosphamide in Rats Tongue Mucosa: Histological and Immunohistochemical Study. Journal of Physics: ConferenceSeries, 1279(1), 012014. https://doi.org/10.1088/1742- 6596/1279/1/012014
31. Santosa, D., Pangarsa, E.A., Setiawan, B., Naibaho, R.M., Rizky, D., Dharmana, E., et al. (2021). Establishing the hematopoietic stem cell transplant (HSCT) in a developing country; the journey of HSCT in Semarang, Indonesia. Bone Marrow Transplantation, 56(1), 270- 273. https://doi.org/10.1038/s41409-020-0973-7
32. Shahbaz, M., Zaheer, N., Sagheer, A., Arshad, A.I., Zaheer, U., Alam, M.K. (2017). Role of Green Tea Extract (Camellia sinensis) in Prevention of Nicotine-Induced Inflammatory and Epithelial Changes in Buccal Mucosa of Albino Rats. International Medical Journal, 24(2), 230
33. Sonis, S.T., Elting, L.S., Keefe, D., Peterson, D.E., Schubert, M., Hauer Jensen, M., et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. (2004). Cancer: Interdisciplinary International Journal of the American Cancer Society, 100(S9). https://doi.org/10.1002/cncr.20162
34. Sonis, S.T. (2004). The pathobiology of mucositis. Nature Reviews Cancer, 4(4), 277-284 Trevenzoli, D.A.M., Cock, N.R.O.S., De Souza, L.N.G., Vaz, S.L.D.A., Leite, M.F., De Barros, L,A,P., et al. (2018). Green Tea: a Potential Radioprotective Agent for the Oral Mucosa. Oral surgery, oral medicine, oral pathology and oral radiology, 126(3), 175-176