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Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats

Year 2020, Volume 42, Issue 4, 363 - 372, 13.07.2020
https://doi.org/10.20515/otd.549371

Abstract

To investigate the therapeutic potential of Morus Nigra on the mucositis of digestive system induced via 5-fluorouracil in rats. A total of 26 rats were divided into 4 groups as control (C), mucositis (M), Morus nigra extract-1(MN-1) and Morus nigra extract-2 (MN-2). Mucositis was induced by intraperitoneal injection of 60 mg/kg 5-fluorouracil (5-FU). The antioxidant enzyme levels in blood samples were analysed by ELISA. Histological analysis and immunohistochemical staining for NF-kB and TNF-α were done. Increased oxidative markers were found in mucositis group and increased antioxidative status was found in MN-1 and MN-2 groups. All histochemical analyses suggested that 5-FU causes intestinal degeneration; the MN-1 extract reduced this degeneration but did not completely treat it. The therapeutic potential of MN-2 extract was lower than the MN-1. Results of the present study suggest that, though partly, MN-1 extract in particular may have biochemically and histologically positive effects against experimental mucositis induced by 5-FU in rats.

References

  • 1. Alterio D, Jereczek-Fossa BA, Piperno G, Laudati A, Ferrari AM, Giugliano G, et al. Oral cavity overinfection during non surgical cancer therapies: Review of the literature. International Journal of Clinical Dentistry. 2008:123.
  • 2. Lalla R, Bowen J, Barasch A, Elting L, Epstein J, Keefe D, et al. Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(10):1453-61.
  • 3. Silverman Jr S. Diagnosis and management of oral mucositis. The journal of supportive oncology. 2007;5(2 Suppl 1):13-21.
  • 4. Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet F, Barasch A, et al. Patient‐reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy. Cancer. 2008;113(10):2704-13.
  • 5. Lalla RV, Schubert MM, Bensadoun R-J, Keefe D. Anti-inflammatory agents in the management of alimentary mucositis. Supportive Care in Cancer. 2006;14(6):558-65.
  • 6. Shameem R, Lacouture M, Wu S. Incidence and risk of high-grade stomatitis with mTOR inhibitors in cancer patients. Cancer investigation. 2015;33(3):70-7.
  • 7. Vera-Llonch M, Oster G, Ford CM, Lu J, Sonis S. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Supportive Care in Cancer. 2007;15(5):491-6.
  • 8. Ye Y, Carlsson G, Agholme MB, Karlsson-Sjöberg J, Yucel-Lindberg T, Pütsep K, et al. Pretherapeutic plasma pro-and anti-inflammatory mediators are related to high risk of oral mucositis in pediatric patients with acute leukemia: a prospective cohort study. PLoS One. 2013;8(5):e64918.
  • 9. Stokman M, Spijkervet F, Boezen H, Schouten J, Roodenburg J, De Vries E. Preventive intervention possibilities in radiotherapy-and chemotherapy-induced oral mucositis: results of meta-analyses. Journal of dental research. 2006;85(8):690-700.
  • 10. Walsh L. Clinical assessment and management of the oral environment in the oncology patient. Australian dental journal. 2010;55(s1):66-77.
  • 11. Bowen JM, Gibson RJ, Keefe DM. Animal models of mucositis: implications for therapy. The journal of supportive oncology. 2011;9(5):161-8.
  • 12. Can G, Enç N, Akkaya S. Onkoloji hemşireliğinde kanıta dayalı semptom yönetimi. Konsensus. 2007;7:64-6.
  • 13. Harris DJ, Harriman A, Cashavelly BJ, Cathy Maxwell R. Putting evidence into practice®: Evidence-based interventions for the management of oral mucositis. Clinical journal of oncology nursing. 2008;12(1):141.
  • 14. de Queiroz GT, Santos TR, Macedo R, Peters VM, Leite MN, de Oliveira Guerra M. Efficacy of Morus nigra L. on reproduction in female Wistar rats. Food and chemical toxicology. 2012;50(3-4):816-22.
  • 15. Ercisli S, Orhan E. Chemical composition of white (Morus alba), red (Morus rubra) and black (Morus nigra) mulberry fruits. Food Chemistry. 2007;103(4):1380-4.
  • 16. Hassimotto NMA, Genovese MI, Lajolo FM. Absorption and metabolism of cyanidin-3-glucoside and cyanidin-3-rutinoside extracted from wild mulberry (Morus nigra L.) in rats. Nutrition research. 2008;28(3):198-207.
  • 17. Jain P, Keservani R, Dahima R. I-VIVO CHARACTERIZATIO OF HYDROGEL FOR TREATME T OF CHEMO-RADIOTHERAPY I DUCED ORAL MUCOSITIS. 2010.
  • 18. Aras MH, Sezer U, Erkilic S, Demir T, Dagli SN. Effect of dietary boron on 5-fluorouracil induced oral mucositis in rats. European journal of dentistry. 2013;7(3):310.
  • 19. Lima V, Brito G, Cunha F, Rebouças C, Falcão B, Augusto R, et al. Effects of the tumour necrosis factor‐α inhibitors pentoxifylline and thalidomide in short‐term experimental oral mucositis in hamsters. European journal of oral sciences. 2005;113(3):210-7.
  • 20. Tanideh N, Tavakoli P, Saghiri MA, Garcia-Godoy F, Amanat D, Tadbir AA, et al. Healing acceleration in hamsters of oral mucositis induced by 5-fluorouracil with topical Calendula officinalis. Oral surgery, oral medicine, oral pathology and oral radiology. 2013;115(3):332-8.
  • 21. Cool JC, Dyer JL, Xian CJ, Butler RN, Geier MS, Howarth GS. Pre-treatment with insulin-like growth factor-I partially ameliorates 5-fluorouracil-induced intestinal mucositis in rats. Growth hormone & IGF research. 2005;15(1):72-82.
  • 22. Huang T-Y, Chu H-C, Lin Y-L, Ho W-H, Hou H-S, Chao Y-C, et al. Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model. Biochemical and biophysical research communications. 2009;389(4):634-9.
  • 23. Renck D, Santos AA, Machado P, Petersen GO, Lopes TG, Santos DS, et al. Human uridine phosphorylase-1 inhibitors: a new approach to ameliorate 5-fluorouracil-induced intestinal mucositis. Investigational new drugs. 2014;32(6):1301-7.
  • 24. Al-Asmari A, Al-Zahrani A, Khan A, Al-Shahrani H, Ali Al Amri M. Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study. Human & experimental toxicology. 2016;35(1):10-20.
  • 25. Cawley MM, Benson LM. Current trends in managing oral mucositis. Clinical journal of oncology nursing. 2005;9(5).
  • 26. Elting L, Keefe D, Peterson D, Schubert M, Hauer-Jensen M, Bekele B, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 Suppl):1995-2025.
  • 27. Chen H, Pu J, Liu D, Yu W, Shao Y, Yang G, et al. Anti-inflammatory and antinociceptive properties of flavonoids from the fruits of black mulberry (Morus nigra L.). PloS one. 2016;11(4):e0153080.
  • 28. Feng R-Z, Wang Q, Tong W-Z, Xiong J, Wei Q, Zhou W-H, et al. Extraction and antioxidant activity of flavonoids of Morus nigra. International journal of clinical and experimental medicine. 2015;8(12):22328.
  • 29. Arfan M, Khan R, Rybarczyk A, Amarowicz R. Antioxidant activity of mulberry fruit extracts. International journal of molecular sciences. 2012;13(2):2472-80.
  • 30. Turgut NH, Mert DG, Kara H, Egilmez HR, Arslanbas E, Tepe B, et al. Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of d-galactose-induced aging mice. Pharmaceutical biology. 2016;54(6):1052-64.
  • 31. Y.P M. Efficiacy of the fruits of black mulberry (Morus nigra L.) for pharyngitis. Xinjiang J Tradit Chin Med. 2002;20:83-4.
  • 32. Wang Z, Xiao G, Liu X, Tang C, Luo G, Wu F. Anti-inflammatory activity of anthocyanins from mulberry on adjuvant-injuced arthritis. Chin J Public Health. 2009:181-3.
  • 33. Sarkar S, Mazumder S, J Saha S, Bandyopadhyay U. Management of inflammation by natural polyphenols: A comprehensive mechanistic update. Current medicinal chemistry. 2016;23(16):1657-95.
  • 34. Chi YS, Lim H, Park H, Kim HP. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochemical pharmacology. 2003;66(7):1271-8.
  • 35. Shiota A, Hada T, Baba T, Sato M, Yamanaka-Okumura H, Yamamoto H, et al. Protective effects of glycoglycerolipids extracted from spinach on 5-fluorouracil induced intestinal mucosal injury. The Journal of Medical Investigation. 2010;57(3, 4):314-20.

Morus Nigra'nın sıçanlarda 5-florourasil ile oluşturulmuş gastrointestinal mukozite karşı olası tedavi ediciliği

Year 2020, Volume 42, Issue 4, 363 - 372, 13.07.2020
https://doi.org/10.20515/otd.549371

Abstract

Bu çalışmanın amacı sıçan gastrointestinal mukozasında 5-florourasil ile oluşturulmuş mukozit üzerine Morus nigra ekstresinin olası tedavi edici etkisini araştırmaktır.Toplam 26 adet sıçan eşit olarak kontrol, mukozit, mukozit+morus nigra ekstre 1 (MN-1) ve mukozit + morus nigra ekstre 2 (MN-2) olarak bölünmüştür. Mukozit sıçanlarda 60 mg/kg 5-fluorourasilin (5-FU) intraperitoneal olarak enjeksiyonuyla oluşturulmuştur. ELISA ile kandaki oksidan ve antioksidan seviyeleri ölçüldü. Histokimyasal ve immunohistokimyasal boyamalar (NF-kB ve TNF-α antikorları için) yapıldı.  Mukozit grubunda artmış oksidatif stres belirteçleri görülürken Morus nigra ekstresi verilen gruplarda antioksidan belirteçlerin arttığı saptandı. Histokimyasal olarak 5-FU'nun mukozit oluşturduğu ve MN-1 ekstresinin tam olarak olmasa da tedavi edici olduğu gösterildi. MN-1 ekstresi MN-2 ekstresine göre daha iyi bir tedavi edici ajan olduğu belirlendi. Sonuç olarak bu çalışmada 5-FU ile oluşturulmuş mukozite karşı MN-1 ekstresinin kısmi olarak tedavi edici olduğu biyokimyasal ve histopatolojik olarak gösterildi.

References

  • 1. Alterio D, Jereczek-Fossa BA, Piperno G, Laudati A, Ferrari AM, Giugliano G, et al. Oral cavity overinfection during non surgical cancer therapies: Review of the literature. International Journal of Clinical Dentistry. 2008:123.
  • 2. Lalla R, Bowen J, Barasch A, Elting L, Epstein J, Keefe D, et al. Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120(10):1453-61.
  • 3. Silverman Jr S. Diagnosis and management of oral mucositis. The journal of supportive oncology. 2007;5(2 Suppl 1):13-21.
  • 4. Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet F, Barasch A, et al. Patient‐reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy. Cancer. 2008;113(10):2704-13.
  • 5. Lalla RV, Schubert MM, Bensadoun R-J, Keefe D. Anti-inflammatory agents in the management of alimentary mucositis. Supportive Care in Cancer. 2006;14(6):558-65.
  • 6. Shameem R, Lacouture M, Wu S. Incidence and risk of high-grade stomatitis with mTOR inhibitors in cancer patients. Cancer investigation. 2015;33(3):70-7.
  • 7. Vera-Llonch M, Oster G, Ford CM, Lu J, Sonis S. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Supportive Care in Cancer. 2007;15(5):491-6.
  • 8. Ye Y, Carlsson G, Agholme MB, Karlsson-Sjöberg J, Yucel-Lindberg T, Pütsep K, et al. Pretherapeutic plasma pro-and anti-inflammatory mediators are related to high risk of oral mucositis in pediatric patients with acute leukemia: a prospective cohort study. PLoS One. 2013;8(5):e64918.
  • 9. Stokman M, Spijkervet F, Boezen H, Schouten J, Roodenburg J, De Vries E. Preventive intervention possibilities in radiotherapy-and chemotherapy-induced oral mucositis: results of meta-analyses. Journal of dental research. 2006;85(8):690-700.
  • 10. Walsh L. Clinical assessment and management of the oral environment in the oncology patient. Australian dental journal. 2010;55(s1):66-77.
  • 11. Bowen JM, Gibson RJ, Keefe DM. Animal models of mucositis: implications for therapy. The journal of supportive oncology. 2011;9(5):161-8.
  • 12. Can G, Enç N, Akkaya S. Onkoloji hemşireliğinde kanıta dayalı semptom yönetimi. Konsensus. 2007;7:64-6.
  • 13. Harris DJ, Harriman A, Cashavelly BJ, Cathy Maxwell R. Putting evidence into practice®: Evidence-based interventions for the management of oral mucositis. Clinical journal of oncology nursing. 2008;12(1):141.
  • 14. de Queiroz GT, Santos TR, Macedo R, Peters VM, Leite MN, de Oliveira Guerra M. Efficacy of Morus nigra L. on reproduction in female Wistar rats. Food and chemical toxicology. 2012;50(3-4):816-22.
  • 15. Ercisli S, Orhan E. Chemical composition of white (Morus alba), red (Morus rubra) and black (Morus nigra) mulberry fruits. Food Chemistry. 2007;103(4):1380-4.
  • 16. Hassimotto NMA, Genovese MI, Lajolo FM. Absorption and metabolism of cyanidin-3-glucoside and cyanidin-3-rutinoside extracted from wild mulberry (Morus nigra L.) in rats. Nutrition research. 2008;28(3):198-207.
  • 17. Jain P, Keservani R, Dahima R. I-VIVO CHARACTERIZATIO OF HYDROGEL FOR TREATME T OF CHEMO-RADIOTHERAPY I DUCED ORAL MUCOSITIS. 2010.
  • 18. Aras MH, Sezer U, Erkilic S, Demir T, Dagli SN. Effect of dietary boron on 5-fluorouracil induced oral mucositis in rats. European journal of dentistry. 2013;7(3):310.
  • 19. Lima V, Brito G, Cunha F, Rebouças C, Falcão B, Augusto R, et al. Effects of the tumour necrosis factor‐α inhibitors pentoxifylline and thalidomide in short‐term experimental oral mucositis in hamsters. European journal of oral sciences. 2005;113(3):210-7.
  • 20. Tanideh N, Tavakoli P, Saghiri MA, Garcia-Godoy F, Amanat D, Tadbir AA, et al. Healing acceleration in hamsters of oral mucositis induced by 5-fluorouracil with topical Calendula officinalis. Oral surgery, oral medicine, oral pathology and oral radiology. 2013;115(3):332-8.
  • 21. Cool JC, Dyer JL, Xian CJ, Butler RN, Geier MS, Howarth GS. Pre-treatment with insulin-like growth factor-I partially ameliorates 5-fluorouracil-induced intestinal mucositis in rats. Growth hormone & IGF research. 2005;15(1):72-82.
  • 22. Huang T-Y, Chu H-C, Lin Y-L, Ho W-H, Hou H-S, Chao Y-C, et al. Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model. Biochemical and biophysical research communications. 2009;389(4):634-9.
  • 23. Renck D, Santos AA, Machado P, Petersen GO, Lopes TG, Santos DS, et al. Human uridine phosphorylase-1 inhibitors: a new approach to ameliorate 5-fluorouracil-induced intestinal mucositis. Investigational new drugs. 2014;32(6):1301-7.
  • 24. Al-Asmari A, Al-Zahrani A, Khan A, Al-Shahrani H, Ali Al Amri M. Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study. Human & experimental toxicology. 2016;35(1):10-20.
  • 25. Cawley MM, Benson LM. Current trends in managing oral mucositis. Clinical journal of oncology nursing. 2005;9(5).
  • 26. Elting L, Keefe D, Peterson D, Schubert M, Hauer-Jensen M, Bekele B, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(9 Suppl):1995-2025.
  • 27. Chen H, Pu J, Liu D, Yu W, Shao Y, Yang G, et al. Anti-inflammatory and antinociceptive properties of flavonoids from the fruits of black mulberry (Morus nigra L.). PloS one. 2016;11(4):e0153080.
  • 28. Feng R-Z, Wang Q, Tong W-Z, Xiong J, Wei Q, Zhou W-H, et al. Extraction and antioxidant activity of flavonoids of Morus nigra. International journal of clinical and experimental medicine. 2015;8(12):22328.
  • 29. Arfan M, Khan R, Rybarczyk A, Amarowicz R. Antioxidant activity of mulberry fruit extracts. International journal of molecular sciences. 2012;13(2):2472-80.
  • 30. Turgut NH, Mert DG, Kara H, Egilmez HR, Arslanbas E, Tepe B, et al. Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status of d-galactose-induced aging mice. Pharmaceutical biology. 2016;54(6):1052-64.
  • 31. Y.P M. Efficiacy of the fruits of black mulberry (Morus nigra L.) for pharyngitis. Xinjiang J Tradit Chin Med. 2002;20:83-4.
  • 32. Wang Z, Xiao G, Liu X, Tang C, Luo G, Wu F. Anti-inflammatory activity of anthocyanins from mulberry on adjuvant-injuced arthritis. Chin J Public Health. 2009:181-3.
  • 33. Sarkar S, Mazumder S, J Saha S, Bandyopadhyay U. Management of inflammation by natural polyphenols: A comprehensive mechanistic update. Current medicinal chemistry. 2016;23(16):1657-95.
  • 34. Chi YS, Lim H, Park H, Kim HP. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochemical pharmacology. 2003;66(7):1271-8.
  • 35. Shiota A, Hada T, Baba T, Sato M, Yamanaka-Okumura H, Yamamoto H, et al. Protective effects of glycoglycerolipids extracted from spinach on 5-fluorouracil induced intestinal mucosal injury. The Journal of Medical Investigation. 2010;57(3, 4):314-20.

Details

Primary Language English
Subjects Health Care Sciences and Services
Journal Section ORİJİNAL MAKALE
Authors

Semra YİĞİTASLAN This is me (Primary Author)
ESKISEHIR OSMANGAZI UNIVERSITY
0000-0001-6722-2394
Türkiye


Ayşe ÖZKARAMAN
ESKISEHIR OSMANGAZI UNIVERSITY
0000-0002-0507-4100


Ayfer AÇIKGÖZ
ESKISEHIR OSMANGAZI UNIVERSITY
0000-0002-7507-3824


Güler BALCI ALPARSLAN
ESKISEHIR OSMANGAZI UNIVERSITY
0000-0003-3734-3843


Çiğdem TOPRAK This is me
ESKISEHIR OSMANGAZI UNIVERSITY
0000-0003-3718-5195


Fatih GÖGER
ESKISEHIR OSMANGAZI UNIVERSITY
0000-0002-9665-0256


Erhan SAHİN
ESKISEHIR OSMANGAZI UNIVERSITY
0000-0003-2152-0542
Türkiye

Publication Date July 13, 2020
Published in Issue Year 2020, Volume 42, Issue 4

Cite

Bibtex @research article { otd549371, journal = {Osmangazi Tıp Dergisi}, issn = {1305-4953}, eissn = {2587-1579}, address = {}, publisher = {Eskişehir Osmangazi University}, year = {2020}, volume = {42}, pages = {363 - 372}, doi = {10.20515/otd.549371}, title = {Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats}, key = {cite}, author = {Yiğitaslan, Semra and Özkaraman, Ayşe and Açıkgöz, Ayfer and Balcı Alparslan, Güler and Toprak, Çiğdem and Göger, Fatih and Sahin, Erhan} }
APA Yiğitaslan, S. , Özkaraman, A. , Açıkgöz, A. , Balcı Alparslan, G. , Toprak, Ç. , Göger, F. & Sahin, E. (2020). Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats . Osmangazi Tıp Dergisi , 42 (4) , 363-372 . DOI: 10.20515/otd.549371
MLA Yiğitaslan, S. , Özkaraman, A. , Açıkgöz, A. , Balcı Alparslan, G. , Toprak, Ç. , Göger, F. , Sahin, E. "Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats" . Osmangazi Tıp Dergisi 42 (2020 ): 363-372 <https://dergipark.org.tr/en/pub/otd/issue/55942/549371>
Chicago Yiğitaslan, S. , Özkaraman, A. , Açıkgöz, A. , Balcı Alparslan, G. , Toprak, Ç. , Göger, F. , Sahin, E. "Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats". Osmangazi Tıp Dergisi 42 (2020 ): 363-372
RIS TY - JOUR T1 - Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats AU - Semra Yiğitaslan , Ayşe Özkaraman , Ayfer Açıkgöz , Güler Balcı Alparslan , Çiğdem Toprak , Fatih Göger , Erhan Sahin Y1 - 2020 PY - 2020 N1 - doi: 10.20515/otd.549371 DO - 10.20515/otd.549371 T2 - Osmangazi Tıp Dergisi JF - Journal JO - JOR SP - 363 EP - 372 VL - 42 IS - 4 SN - 1305-4953-2587-1579 M3 - doi: 10.20515/otd.549371 UR - https://doi.org/10.20515/otd.549371 Y2 - 2019 ER -
EndNote %0 Osmangazi Journal of Medicine Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats %A Semra Yiğitaslan , Ayşe Özkaraman , Ayfer Açıkgöz , Güler Balcı Alparslan , Çiğdem Toprak , Fatih Göger , Erhan Sahin %T Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats %D 2020 %J Osmangazi Tıp Dergisi %P 1305-4953-2587-1579 %V 42 %N 4 %R doi: 10.20515/otd.549371 %U 10.20515/otd.549371
ISNAD Yiğitaslan, Semra , Özkaraman, Ayşe , Açıkgöz, Ayfer , Balcı Alparslan, Güler , Toprak, Çiğdem , Göger, Fatih , Sahin, Erhan . "Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats". Osmangazi Tıp Dergisi 42 / 4 (July 2020): 363-372 . https://doi.org/10.20515/otd.549371
AMA Yiğitaslan S. , Özkaraman A. , Açıkgöz A. , Balcı Alparslan G. , Toprak Ç. , Göger F. , Sahin E. Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats. Osmangazi Tıp Dergisi. 2020; 42(4): 363-372.
Vancouver Yiğitaslan S. , Özkaraman A. , Açıkgöz A. , Balcı Alparslan G. , Toprak Ç. , Göger F. , Sahin E. Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats. Osmangazi Tıp Dergisi. 2020; 42(4): 363-372.
IEEE S. Yiğitaslan , A. Özkaraman , A. Açıkgöz , G. Balcı Alparslan , Ç. Toprak , F. Göger and E. Sahin , "Therapeutic potential of morus nigra on 5-fluorouracil-induced gastrointestinal mucositis in rats", Osmangazi Tıp Dergisi, vol. 42, no. 4, pp. 363-372, Jul. 2020, doi:10.20515/otd.549371

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