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Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats

Yıl 2025, Cilt: 35 Sayı: 1, 17 - 28, 28.03.2025
https://doi.org/10.26650/Tr-ENT.2025.1588521

Öz

Objective: We aimed to investigate the radioprotective effects of apigenin on the submandibular gland of rats in this study.

Material and Methods: Four experimental groups were composed of 10 rats in each group. Rats in Group 1 were administered radiotherapy solely and administered no drug. Apigenin dissolved in dimethyl sulfoxide (DMSO) at a dose of 25 mg/kg 48 h before radiotherapy administration to Group 2. In Group 3, only 1.66 ml/kg of DMSO was given intraperitoneally. Group 4 did not receive radiotherapy, and apigenin dissolved in DMSO was administered intraperitoneally at a dose of 25 mg/kg. Intraperitoneal drug admin istrations were performed simultaneously in all groups, and all rats were sacrificed 48 h after radiotherapy administration. Existence of necrosis, acinar damage, ductal damage, vacuolisation, and TNFα expression were scored as 0,1,2,3.

Results: As a result of the statistical analyses, it was observed that Group 2 was significantly protected compared to Group 1 in terms of necrosis, acinar damage and vacuolisation (p values: 0.004, 0.003, 0.001, respectively). Similarly, TNFα expression was also significantly decreased (p<0.001). In comparisons between Groups 1 and 3, there was no significant difference in terms of necrosis and acinar damage (p values: 0.328, 0.325, respectively), while the difference between the two groups was significant in terms of vacuolisation and TNFα expression (p values: 0.005, 0.02, respectively).

Conclusion: Apigenin was found to be an effective radioprotectant agent in terms of preventing necrosis, acinar damage and vacuolisation, histopathologically. It has been shown that apigeninDMSO solution decreases TNFα levels, immunohistochemically.

Kaynakça

  • Nguyen NP, SaLLah S, KarLsson U, Antoine JE. Combined chemotherapy and radiation therapy for head and neck maLignancies: quaLity of Life issues. Cancer 2002;94(4):1131-41. google scholar
  • Salehi B, Venditti A, Sharifi-Rad M, KrşgieL D, Sharifi-Rad J, Durazzo A, et al. The Therapeutic PotentiaL of Apigenin. İnt J MoL Sci 2019;20(6):1305. google scholar
  • Rithidech KN, Tungjai M, Whorton EB. Protective effect of apigenin on radiation-induced chromosomal damage in human Lymphocytes. Mutat Res 2005;585(l-2):96-104. google scholar
  • Begum N, Rajendra Prasad N, Kanimozhi G, AgiLan B. Apigenin prevents gamma radiation-induced gastrointestinal damages by modulating inflammatory and apoptotic signalling mediators. Nat Prod Res 2022;36(6):1631-5. google scholar
  • Lopez-Jornet P, Gömez-Garcîa F, Garcıa Carrillo N, Valle-Rodrıguez E, Xerafin A, Vicente-Ortega V. Radioprotective effects of Lycopene and curcumin during local irradiation of parotid glands in Sprague Dawley rats. Br J Oral Maxillofac Surg 2016;54(3):275-9. google scholar
  • Kim JH, Kim KM, Jung MH, Jung JH, Kang KM, Jeong BK, et al. Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats. Oncotarget 2016;7(20):29143-53. google scholar
  • Vissink A, van Luijk P, Langendijk JA, Coppes RP. Current ideas to reduce or salvage radiation damage to salivary glands. Oral Dis 2015;2l(l):1-10. google scholar
  • Elsurer C, Çelik ZE, Yavas G, Yavas C. Spironolactone ameliorates the radiation-induced late fibrosis in salivary glands in a rat model. International J Radiation Res 2020;18(l):149-55. google scholar
  • Kashima HK, Kirkham WR, Andrews JR. Postirradiation sialoadentis. Am J Roentgenol 1965;94:271-91. google scholar
  • Nagler RM. The enigmatic mechanism of irradiation-induced damage to the majör salivary glands. Oral Dis 2002;8(3):141-6. google scholar
  • Alfouzan AF. Radiation therapy in head and neck cancer. Saudi Med J 2021;42(3):247-54. google scholar
  • De la Cal C, Fernândez-Solari J, Mohn C, Prestifilippo J, Pugnaloni A, Medina V et al. Radiation produces irreversible chronic dysfunction in the submandibular glands of the rat. Öpen Dent J 2012;6:8-13. google scholar
  • Krishnan M, Tennavan A, Saraswathy S, Sekhri T, Singh AK, Nair V. Acute Radiation-induced Changes in Sprague-Dawley Rat Submandibular Glands: A Histomorphometric Analysis. World J Oncol 2017;8(2):45-52. google scholar
  • Kim JY, An CH, Kim JY, Jung JK. Experimental Animal Model Systems for Understanding Salivary Secretory Disorders. int J Mol Sci 2020;21(22):8423. google scholar
  • Rosen EM, Day R, Singh VK. New approaches to radiation protection. Front Oncol 2015;4:381. google scholar
  • Nagler R, Marmary Y, Golan E, Chevion M. Novel protection strategy against X-ray-induced damage to salivary glands. Radiat Res 1998;149(3):271-6. google scholar
  • Teymoortash A, Müller F, Juricko J, Bieker M, Mandic R, Librizzi D et al. Botulinum toxin prevents radiotherapy-induced salivary gland damage. Oral Oncol 2009;45(8):737-9. google scholar
  • Fischer N, Seo EJ, Efferth T. Prevention from radiation damage by natural products. Phytomedicine 2018;47:192-200. google scholar
  • Gradolatto A, Basly JP Berges R, Teyssier C, Chagnon MC, Siess MH, Canivenc-Lavier MC. Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metab Dispos 2005;33(l):49-54. google scholar
  • Raskovic A, Gigov S, Capo I, Paut Kusturica M, Milijasevic B, Kojic-Damjanov S, Martin N. Antioxidative and protective actions of apigenin in a paracetamol-induced hepatotoxicity rat model. Eur J Drug Metab Pharmacokinet 2017;42(5):849-56. google scholar
  • Begüm N, Prasad NR, Thayalan K. Apigenin protects gamma-radiation induced oxidative stress, hematological changes and animal survival in whole body irradiated Swiss albino mice. Int J Nutrition Pharmacol Neurological Dis 2012;2(l):45-52. google scholar
  • Singh P, Mishra SK, Noel S, Sharma S, Rath SK. Acute exposure of apigenin induces hepatotoxicity in Swiss mice. PLoS One 2012;7(2):31964. google scholar
  • Peng R, Zhang W, Zuo Z, Shan Y, Liu X, Tang Y, et al. Dimethyl sulfoxide, a potent oral radioprotective agent, confers radioprotection of hematopoietic stem and progenitor cells independent of apoptosis. Free Radic Biol Med 2020;153:1-11. google scholar
  • Yang C, Tang H, Wang L, Peng R, Bai F, Shan Y, et al. Dimethyl sulfoxide prevents radiation-induced oral mucositis through facilitating DNA double-strand break repair in epithelial stem cells. Int J Radiat Oncol Biol Phys 2018;102(5):1577-89. google scholar
  • Nagler RM, Baum BJ, Fox PC. Acute effects of X irradiation on the function of rat salivary glands. Radiat Res 1993;136(l):42-7. google scholar
  • Silvers AR, Som PM. Salivary glands. Radiol Clin North Am 1998;36(5):941-vi. google scholar
  • Choi EM. Apigenin increases osteoblastic differentiation and inhibits tumor necrosis factor-alpha-induced production of interleukin-6 and nitric oxide in osteoblastic MC3T3-E1 cells. Pharmazie 2007;62(3):216-20. google scholar
  • Park CH, Min SY, Yu HW, Kim K, Kim S, Lee HJ, et al. Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-allergic, anti-inflammatory, and skin-protective activities. Int J Mol Sci 2020;21(13):4620. google scholar
  • Limaye A, Hail BE, Zhang L, Cho A, Prochazkova M, Zheng C, et al. Targeted TNF-a overexpression drives salivary gland inflammation. J Dent Res 2019;98(6):713-9. google scholar
Yıl 2025, Cilt: 35 Sayı: 1, 17 - 28, 28.03.2025
https://doi.org/10.26650/Tr-ENT.2025.1588521

Öz

Kaynakça

  • Nguyen NP, SaLLah S, KarLsson U, Antoine JE. Combined chemotherapy and radiation therapy for head and neck maLignancies: quaLity of Life issues. Cancer 2002;94(4):1131-41. google scholar
  • Salehi B, Venditti A, Sharifi-Rad M, KrşgieL D, Sharifi-Rad J, Durazzo A, et al. The Therapeutic PotentiaL of Apigenin. İnt J MoL Sci 2019;20(6):1305. google scholar
  • Rithidech KN, Tungjai M, Whorton EB. Protective effect of apigenin on radiation-induced chromosomal damage in human Lymphocytes. Mutat Res 2005;585(l-2):96-104. google scholar
  • Begum N, Rajendra Prasad N, Kanimozhi G, AgiLan B. Apigenin prevents gamma radiation-induced gastrointestinal damages by modulating inflammatory and apoptotic signalling mediators. Nat Prod Res 2022;36(6):1631-5. google scholar
  • Lopez-Jornet P, Gömez-Garcîa F, Garcıa Carrillo N, Valle-Rodrıguez E, Xerafin A, Vicente-Ortega V. Radioprotective effects of Lycopene and curcumin during local irradiation of parotid glands in Sprague Dawley rats. Br J Oral Maxillofac Surg 2016;54(3):275-9. google scholar
  • Kim JH, Kim KM, Jung MH, Jung JH, Kang KM, Jeong BK, et al. Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats. Oncotarget 2016;7(20):29143-53. google scholar
  • Vissink A, van Luijk P, Langendijk JA, Coppes RP. Current ideas to reduce or salvage radiation damage to salivary glands. Oral Dis 2015;2l(l):1-10. google scholar
  • Elsurer C, Çelik ZE, Yavas G, Yavas C. Spironolactone ameliorates the radiation-induced late fibrosis in salivary glands in a rat model. International J Radiation Res 2020;18(l):149-55. google scholar
  • Kashima HK, Kirkham WR, Andrews JR. Postirradiation sialoadentis. Am J Roentgenol 1965;94:271-91. google scholar
  • Nagler RM. The enigmatic mechanism of irradiation-induced damage to the majör salivary glands. Oral Dis 2002;8(3):141-6. google scholar
  • Alfouzan AF. Radiation therapy in head and neck cancer. Saudi Med J 2021;42(3):247-54. google scholar
  • De la Cal C, Fernândez-Solari J, Mohn C, Prestifilippo J, Pugnaloni A, Medina V et al. Radiation produces irreversible chronic dysfunction in the submandibular glands of the rat. Öpen Dent J 2012;6:8-13. google scholar
  • Krishnan M, Tennavan A, Saraswathy S, Sekhri T, Singh AK, Nair V. Acute Radiation-induced Changes in Sprague-Dawley Rat Submandibular Glands: A Histomorphometric Analysis. World J Oncol 2017;8(2):45-52. google scholar
  • Kim JY, An CH, Kim JY, Jung JK. Experimental Animal Model Systems for Understanding Salivary Secretory Disorders. int J Mol Sci 2020;21(22):8423. google scholar
  • Rosen EM, Day R, Singh VK. New approaches to radiation protection. Front Oncol 2015;4:381. google scholar
  • Nagler R, Marmary Y, Golan E, Chevion M. Novel protection strategy against X-ray-induced damage to salivary glands. Radiat Res 1998;149(3):271-6. google scholar
  • Teymoortash A, Müller F, Juricko J, Bieker M, Mandic R, Librizzi D et al. Botulinum toxin prevents radiotherapy-induced salivary gland damage. Oral Oncol 2009;45(8):737-9. google scholar
  • Fischer N, Seo EJ, Efferth T. Prevention from radiation damage by natural products. Phytomedicine 2018;47:192-200. google scholar
  • Gradolatto A, Basly JP Berges R, Teyssier C, Chagnon MC, Siess MH, Canivenc-Lavier MC. Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metab Dispos 2005;33(l):49-54. google scholar
  • Raskovic A, Gigov S, Capo I, Paut Kusturica M, Milijasevic B, Kojic-Damjanov S, Martin N. Antioxidative and protective actions of apigenin in a paracetamol-induced hepatotoxicity rat model. Eur J Drug Metab Pharmacokinet 2017;42(5):849-56. google scholar
  • Begüm N, Prasad NR, Thayalan K. Apigenin protects gamma-radiation induced oxidative stress, hematological changes and animal survival in whole body irradiated Swiss albino mice. Int J Nutrition Pharmacol Neurological Dis 2012;2(l):45-52. google scholar
  • Singh P, Mishra SK, Noel S, Sharma S, Rath SK. Acute exposure of apigenin induces hepatotoxicity in Swiss mice. PLoS One 2012;7(2):31964. google scholar
  • Peng R, Zhang W, Zuo Z, Shan Y, Liu X, Tang Y, et al. Dimethyl sulfoxide, a potent oral radioprotective agent, confers radioprotection of hematopoietic stem and progenitor cells independent of apoptosis. Free Radic Biol Med 2020;153:1-11. google scholar
  • Yang C, Tang H, Wang L, Peng R, Bai F, Shan Y, et al. Dimethyl sulfoxide prevents radiation-induced oral mucositis through facilitating DNA double-strand break repair in epithelial stem cells. Int J Radiat Oncol Biol Phys 2018;102(5):1577-89. google scholar
  • Nagler RM, Baum BJ, Fox PC. Acute effects of X irradiation on the function of rat salivary glands. Radiat Res 1993;136(l):42-7. google scholar
  • Silvers AR, Som PM. Salivary glands. Radiol Clin North Am 1998;36(5):941-vi. google scholar
  • Choi EM. Apigenin increases osteoblastic differentiation and inhibits tumor necrosis factor-alpha-induced production of interleukin-6 and nitric oxide in osteoblastic MC3T3-E1 cells. Pharmazie 2007;62(3):216-20. google scholar
  • Park CH, Min SY, Yu HW, Kim K, Kim S, Lee HJ, et al. Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-allergic, anti-inflammatory, and skin-protective activities. Int J Mol Sci 2020;21(13):4620. google scholar
  • Limaye A, Hail BE, Zhang L, Cho A, Prochazkova M, Zheng C, et al. Targeted TNF-a overexpression drives salivary gland inflammation. J Dent Res 2019;98(6):713-9. google scholar
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Kulak Burun Boğaz
Bölüm Araştırma Makaleleri
Yazarlar

Bekir Büyükçelik 0000-0002-3620-2443

Mustafa Tüz 0000-0002-7680-7105

Özlem Özmen 0000-0002-1835-1082

Yusuf Çağdaş Kumbul 0000-0002-0713-2933

Mehmet Emre Sivrice 0000-0002-2396-6794

Hasan Yasan 0000-0002-5470-6784

Erdoğan Okur 0000-0003-4384-840X

Vural Akın 0000-0002-0050-4837

Yayımlanma Tarihi 28 Mart 2025
Gönderilme Tarihi 20 Kasım 2024
Kabul Tarihi 12 Mart 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 35 Sayı: 1

Kaynak Göster

APA Büyükçelik, B., Tüz, M., Özmen, Ö., Kumbul, Y. Ç., vd. (2025). Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats. The Turkish Journal of Ear Nose and Throat, 35(1), 17-28. https://doi.org/10.26650/Tr-ENT.2025.1588521
AMA Büyükçelik B, Tüz M, Özmen Ö, Kumbul YÇ, Sivrice ME, Yasan H, Okur E, Akın V. Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats. Tr-ENT. Mart 2025;35(1):17-28. doi:10.26650/Tr-ENT.2025.1588521
Chicago Büyükçelik, Bekir, Mustafa Tüz, Özlem Özmen, Yusuf Çağdaş Kumbul, Mehmet Emre Sivrice, Hasan Yasan, Erdoğan Okur, ve Vural Akın. “Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats”. The Turkish Journal of Ear Nose and Throat 35, sy. 1 (Mart 2025): 17-28. https://doi.org/10.26650/Tr-ENT.2025.1588521.
EndNote Büyükçelik B, Tüz M, Özmen Ö, Kumbul YÇ, Sivrice ME, Yasan H, Okur E, Akın V (01 Mart 2025) Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats. The Turkish Journal of Ear Nose and Throat 35 1 17–28.
IEEE B. Büyükçelik, M. Tüz, Ö. Özmen, Y. Ç. Kumbul, M. E. Sivrice, H. Yasan, E. Okur, ve V. Akın, “Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats”, Tr-ENT, c. 35, sy. 1, ss. 17–28, 2025, doi: 10.26650/Tr-ENT.2025.1588521.
ISNAD Büyükçelik, Bekir vd. “Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats”. The Turkish Journal of Ear Nose and Throat 35/1 (Mart 2025), 17-28. https://doi.org/10.26650/Tr-ENT.2025.1588521.
JAMA Büyükçelik B, Tüz M, Özmen Ö, Kumbul YÇ, Sivrice ME, Yasan H, Okur E, Akın V. Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats. Tr-ENT. 2025;35:17–28.
MLA Büyükçelik, Bekir vd. “Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats”. The Turkish Journal of Ear Nose and Throat, c. 35, sy. 1, 2025, ss. 17-28, doi:10.26650/Tr-ENT.2025.1588521.
Vancouver Büyükçelik B, Tüz M, Özmen Ö, Kumbul YÇ, Sivrice ME, Yasan H, Okur E, Akın V. Radioprotective Effect of Apigenin on the Submandibular Gland of Irradiated Rats. Tr-ENT. 2025;35(1):17-28.