Possible protective effect of Zataria multiflora Boiss. on salivary glands in patients with differentiated thyroid carcinoma treated with radioiodine: A randomized, double-blind, placebo-controlled clinical trial

Document Type : Original Article

Authors

1 Research Center for Traditional Medicine and History of Medicine, Department of Persian Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Phytopharmaceuticals (Traditional Pharmacy), Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Nuclear Medicine, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Introduction: The standard treatment for differentiated thyroid carcinoma is post-surgical radioiodine ablation; however, salivary gland damage is prevalent. This study aimed to evaluate the efficacy of Zataria multiflora Boiss. (ZM) aerial part essential oil in protecting salivary glands from post-radioiodine therapy damage in differentiated thyroid cancer patients.
Methods: In this randomized clinical trial, 24 patients with differentiated thyroid cancer were randomly allocated to two groups: 11 patients in the ZM essential oil group and 13 in the placebo group. Patients in the intervention and placebo groups received 20 oral drops three times a day of ZM essential oil or placebo respectively, starting from one week before radioiodine therapy to 4 weeks afterward. Salivary gland function was assessed using scintigraphic parameters before and six months following radioiodine therapy.
Results: Follow-up scintigraphy demonstrated significant decrease in parotid UI in the placebo group (P=0.032) while significant increase in UI (P=0.025) and EF (P=0.042) of the parotid was observed in the ZM group. Comparing changes in functional indices of salivary glands between the two groups after six months revealed significantly better function in parotid UI (P=0.005) and parotid EF (P=0.006) in the ZM group. Substantial damage to parotid UI was significantly less in the ZM group (P=0.044).
Conclusion: Results of this study demonstrated that administration of ZM essential oil to patients with differentiated thyroid cancer may protect the salivary glands from radioiodine injury.

Keywords

Main Subjects


  1. Farhood B, Geraily G, Alizadeh A. Incidence and mortality of various cancers in iran and compare to other countries: a review article. Iran J Public Health. 2018 Mar;47(3):309-16.
  2. Hollingsworth B, Senter L, Zhang X, Brock GN, Jarjour W, Nagy R, Brock P, Coombes KR, Kloos RT, Ringel MD, Sipos J, Lattimer I, Carrau R, Jhiang SM. Risk factors of 131I-induced salivary gland damage in thyroid cancer patients. J Clin Endocrinol Metab. 2016 Nov;101(11):4085-93.
  3. Jung JH, Lee CH, Son SH, Jeong JH, Jeong SY, Lee SW, Lee J, Ahn BC. High prevalence of thyroid disease and role of salivary gland scintigraphy in patients with xerostomia. Nucl Med Mol Imaging. 2017 Jun;51(2):169-77.
  4. Baudin C, Lussey-Lepoutre C, Bressand A, Buffet C, Menegaux F, Soret M, Broggio D, Bassinet C, Huet C, Armengol G, Leenhardt L. Salivary Dysfunctions and Consequences After Radioiodine Treatment for Thyroid Cancer: Protocol for a Self-Controlled Study (START Study). JMIR Res Protoc. 2022 Jul 22;11(7):e35565.
  5. Moreddu E, Baumstarck-Barrau K, Gabriel S, Fakhry N, Sebag F, Mundler O, Chossegros C, Taïeb D. Incidence of salivary side effects after radioiodine treatment using a new specifically-designed questionnaire. Br J Surg . 2017 Jul 1;55(6):609-12.
  6. Fard-Esfahani A, Fallahi B, Karimi M, Beiki D, Saghari M, Emami-Ardekani A, Fard-Esfahani P, Ansari M, Eftekhari M. Changes in salivary gland function following radioiodine therapy of thyroid diseases: A comparison of high-dose therapy for thyroid cancer and low-dose therapy for benign thyroid disease. Iran J Nucl Med. 2015;23(1):1-7.
  7. Verburg FA, Hänscheid H, Luster M. Radioactive iodine (RAI) therapy for metastatic differentiated thyroid cancer. Best Pract Res Clin Endocrinol Metab. 2017 Jun 1;31(3):279-90.
  8. Charalambous A. Seeking optimal management for radioactive iodine therapy-induced adverse effects. Asia-Pac J Oncol Nurs. 2017 Oct 1;4(4):319-22.
  9. Alidadi S, Monfared AS, Amiri M, Zabihi E, Assadollahi E, Gholami A, Moazezi Z, Abedian Z. The efficacy of melatonin against radiotoxicity of iodine-131 and its response to treatment in hyperthyroid patients: a randomized controlled trial. Nucl Med Rev 2022;25(1):31-6
  10. Taheri A, Rostamzadeh A, Gharib A, Fatehi D. Radioprotective effects of Silymarin, a natural medical herb, in modulation and prevention of radiation induced damages. Der Pharm Lett. 2016;8(9):146-50.
  11. Son H, Lee SM, Yoon RG, Lee H, Lee I, Kim S, Chung WY, Lee JW. Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer. Hell J Nucl Med. 2017;20(1):62-70.
  12. Upadhyaya A, Zhou P, Meng Z, Wang P, Zhang G, Jia Q, Tan J, Li X, Hu T, Liu N, Wang S. Radioprotective effect of vitamin E on salivary glands after radioiodine therapy for differentiated thyroid cancer: a randomized-controlled trial. Nucl Med Commun. 2017 Nov 1;38(11):891-903.
  13. Han EJ, Im ST, Ahn G, Lee SH. Radio-protective effects of Thymus quinquecostatus Celak extract in mice. Appl Radiat Isot. 2023 May 30:110881.
  14. Safaei M, Jafarpour SM, Mohseni M, Salimian M, Akbari H, Karami F, Aliasgharzadeh A, Farhood B. Vitamins E and C prevent DNA double-strand breaks in peripheral lymphocytes exposed to radiations from Iodine-131. Indian J Nucl Med. 2018 Jan;33(1):20.
  15. Maier P, Wenz F, Herskind C. Radioprotection of normal tissue cells. Strahlenther Onkol. 2014 Aug 1;190(8):745.
  16. Klubo-Gwiezdzinska J, Costello Jr J, Jensen K, Patel A, Van Nostrand D, Burman KD, Wartofsky L, Vasko V. Amifostine does not protect thyroid cancer cells in DNA damaging in vitro models. Endocr Connect. 2017 Oct;6(7):469.
  17. Christou A, Papastavrou E, Merkouris A, Frangos S, Tamana P, Charalambous A. Clinical studies of nonpharmacological methods to minimize salivary gland damage after radioiodine therapy of differentiated thyroid carcinoma: systematic review. Evid-based Complement Altern Med.2016 Oct;2016.
  18. Ahani N, Sangtarash MH, Eskandani MA, Houshmand M. Zataria multiflora boiss. Essential oil induce apoptosis in two human colon cancer cell lines (HCT116 & SW48). Iran J Public Health. 2020 Apr;49(4):753.
  19. Hajihashemi S, Jafarian T, Ahmadi M, Rahbari A, Ghanbari F. Ameliorative effects of Zataria multiflora hydro-alcoholic extract on gentamicin induced nephrotoxicity in rats. Drug Res. 2018 Jul;68(07):387-94.
  20. Shams MR, Rahimi R, Farjazmand F, editors. Makhzanoladvieh.Tehran; 2012.
  21. Aghili-khorasani MH. Kholase al hekmah. 1st ed. Tehran: Iranian Teb publisher; 2017.
  22. Sharafati Chaleshtori R, Rafieian Kopaei M, Rokni N, Mortezaei S, Sharafati Chaleshtori A. Antioxidant activity of Zataria multiflora hydroalcoholic extract and its antibacterial effect on Staphylococcus aureus. J Maz Univ Med. 2012 Feb 10;21(1):88-94.
  23. Aghamohammadi A, Moslemi D, Akbari J, Ghasemi A, Azadbakht M, Asgharpour A, Hosseinimehr SJ. The effectiveness of Zataria extract mouthwash for the management of radiation-induced oral mucositis in patients: A randomized placebo-controlled double-blind study. Clin Oral Investig. 2018 Jul;22:2263-72.
  24. Mahboubi M. Therapeutic potential of Zataria multiflora boiss in treatment of irritable bowel syndrome (IBS). J Diet Suppl. 2019;16(1):119-28.
  25. Norooznezhad AH, Keshavarz M, Norooznezhad F, Mansouri K. Inhibition of Angiogenesis: A Novel Effect of Zataria Multiflora. Int J Hematol Oncol Stem Cell Res. 2017 Apr 1;11(2):96-101.
  26. Sodouri M, Masoudi Alavi N, Fathizadeh N, Taghizadeh M, Azarbad Z, Memarzadeh M. Effects of Zataria Multi-Flora, Shirazi thyme, on the Severity of Premenstrual Syndrome. Nurs Midwifery Stud. 2013 Dec;2(4):57-63.
  27. Minaiyan M, Sajjadi SE, Amini K. Antiulcer effects of Zataria multiflora Boiss. on indomethacin-induced gastric ulcer in rats. Avicenna J Phytomed. 2018 Sep-Oct;8(5):408-15.
  28. Mahmoodi M, Koohpeyma F, Saki F, Maleksabet A, Zare MA. The protective effect of Zataria multiflora Boiss. hydroalcoholic extract on TNF-α production, oxidative stress, and insulin level in streptozotocin-induced diabetic rats. Avicenna J Phytomed. 2019 Jan-Feb;9(1):72-83.
  29. Hosseinimehr SJ, Mahmoudzadeh A, Ahmadi A, Ashrafi SA, Shafaghati N, Hedayati N. The radioprotective effect of Zataria multiflora against genotoxicity induced by γ irradiation in human blood lymphocytes. Cancer Biother Radiopharm. 2011 Jun;26(3):325-9.
  30. Fatemi F, Asri Y, Rasooli I, Alipoor ShD, Shaterloo M. Chemical composition and antioxidant properties of γ-irradiated Iranian Zataria multiflora extracts. Pharm Biol. 2012 Feb;50(2):232-8.
  31. Sajed H, Sahebkar A, Iranshahi M. Zataria multiflora Boiss. (Shirazi thyme)--an ancient condiment with modern pharmaceutical uses. J Ethnopharmacol. 2013 Feb 13;145(3):686-98.
  32. Hashemipour H, Kermanshahi H, Golian A, Veldkamp T. Effect of thymol and carvacrol feed supplementation on performance, antioxidant enzyme activities, fatty acid composition, digestive enzyme activities, and immune response in broiler chickens. Poult Sci. 2013 Aug;92(8):2059-69.
  33. Arivalagan S, Thomas NS, Kuppusamy T, Namashivayam N. Radioprotective effect of carvacrol against X-Radiation-Induced cellular damage in cultured human peripheral blood lymphocytes. J Environ Pathol Toxicol Oncol. 2015;34(3):263-75.
  34. Abedi SM, Yarmand F, Motallebnejad M, Seyedmajidi M, Moslemi D, Bijani A, Hosseinimehr SJ. Radioprotective effect of thymol against salivary glands dysfunction induced by ionizing radiation in rats. Iran J Pharm Res. 2016 Fall;15(4):861-6.
  35. Majlessi N, Choopani S, Kamalinejad M, Azizi Z. Amelioration of amyloid β-induced cognitive deficits by Zataria multiflora Boiss. essential oil in a rat model of Alzheimer's disease. CNS Neurosci Ther. 2012 Apr;18(4):295-301.
  36. Babaee N, Baradaran M, Mohamadi H, Nooribayat S. Therapeutic effects of Zataria Multiflora essential oil on recurrent oral aphthous lesion. Dent Res J (Isfahan). 2015 Sep-Oct;12(5):456-60.
  37. Klutmann S, Bohuslavizki KH, Kröger S, Bleckmann C, Brenner W, Mester J, Clausen M. Quantitative salivary gland scintigraphy. J Nucl Med Technol. 1999 Mar;27(1):20-6.
  38. Fallahi B, Beiki D, Abedi SM, Saghari M, Fard-Esfahani A, Akhzari F, Mokarami B, Eftekhari M. Does vitamin E protect salivary glands from I-131 radiation damage in patients with thyroid cancer? Nucl Med Commun. 2013 Aug;34(8):777-86.
  39. Upadhyaya A, Meng Z, Wang P, Zhang G, Jia Q, Tan J, Li X, Hu T, Liu N, Zhou P, Wang S, Liu X, Wang H, Zhang C, Zhao F, Yan Z. Effects of first radioiodine ablation on functions of salivary glands in patients with differentiated thyroid cancer. Medicine (Baltimore). 2017 Jun;96(25):e7164.
  40. Jeong SY, Kim HW, Lee SW, Ahn BC, Lee J. Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms. Thyroid. 2013 May;23(5):609-16.
  41. Son H, Lee SM, Yoon RG, Lee H, Lee I, Kim S, Chung WY, Lee JW. Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer. Hell J Nucl Med. 2017 Jan-Apr;20(1):62-70.
  42. Riachy R, Ghazal N, Haidar MB, Elamine A, Nasrallah MP. Early Sialadenitis After Radioactive Iodine Therapy for Differentiated Thyroid Cancer: Prevalence and Predictors. Int J Endocrinol. 2020 Aug 4;2020:8649794.
  43. Tanwar KS, Rana N, Mittal BR, Bhattacharya A. Early Quantification of Salivary Gland Function after Radioiodine Therapy. Indian J Nucl Med. 2021 Jan-Mar;36(1):25-31.
  44. Afzelius P, Nielsen MY, Ewertsen C, Bloch KP. Imaging of the major salivary glands. Clin Physiol Funct Imaging. 2016 Jan;36(1):1-10.
  45. Kang JY, Jang SJ, Lee WW, Jang SJ, Lee YJ, Kim SE. Evaluation of Salivary Gland Dysfunction Using Salivary Gland Scintigraphy in Sjögren's Syndrome Patients and in Thyroid Cancer Patients after Radioactive Iodine Therapy. Nucl Med Mol Imaging. 2011 Sep;45(3):161-8.
  46. Krčálová E, Horáček J, Gabalec F, Žák P, Doležal J. Scintigraphic evaluation of salivary gland function in thyroid cancer patients after radioiodine remnant ablation. Eur J Oral Sci. 2020 Jun;128(3):204-10.
  47. Lv X, Yin L, Wu W, Li N, Zhang R, Li X, Jia Q, Tan J, Wang P, Zheng X, He X, Huang C, Li D, Wang Y, Meng Z. Quantitative Scintigraphy Evaluated the Relationship between 131I Therapy and Salivary Glands Function in DTC Patients: A Retrospective Analysis. J Healthc Eng. 2022 Apr 14;2022:7640405.
  48. Ma D, Yin X, Liu J, Fang Q, He Q, Xiong Y, Gong F. Different medications for preventing 131I-induced salivary gland damage in thyroid cancer patients: a network meta-analysis. Chin Gen Pract. 2021 Oct 20;24(30):3828.
  49. Khazdair MR, Ghorani V, Alavinezhad A, Boskabady MH. Pharmacological effects of Zataria multiflora Boiss L. and its constituents focus on their anti-inflammatory, antioxidant, and immunomodulatory effects. Fundam Clin Pharmacol. 2018 Feb;32(1):26-50.
  50. Khazdair MR, Rajabi O, Balali-Mood M, Beheshti F, Boskabady MH. The effect of Zataria multiflora on pulmonary function tests, hematological and oxidant/antioxidant parameters in sulfur mustard exposed veterans, a randomized doubled-blind clinical trial. Environ Toxicol Pharmacol. 2018 Mar;58:180-8.
  51. Burlage FR, Faber H, Kampinga HH, Langendijk JA, Vissink A, Coppes RP. Enhanced proliferation of acinar and progenitor cells by prophylactic pilocarpine treatment underlies the observed amelioration of radiation injury to parotid glands. Radiother Oncol. 2009 Feb;90(2):253-6.
  52. Zamani N, Shams M, Nimrouzi M, Zarshenas MM, Abolhasani Foroughi A, Fallahzadeh Abarghooei E, Fattahi MR. The effects of Zataria multiflora Boiss. (Shirazi thyme) on nonalcoholic fatty liver disease and insulin resistance: A randomized double-blind placebo-controlled clinical trial. Complement Ther Med. 2018 Dec;41:118-123.