Montelukast attenuates radioactive I131-induced pulmonary damage on rats

Abstract

Purpose: Radioactive I131 (RAI) therapy is a standard method to ablate the remnant thyroidal tissue after total thyroidectomy and its metastases in differentiated thyroid carcinomas; however, I131 also accumulates in nonthyroidal tissue, which may cause adverse effects and limit the I131 dose required for treatment. We hypothesized that montelukast, a known agent with anti-inflammatory and anti-oxidant properties, would ameliorate the radiation-induced histopathological characteristics such as pneumonitis and fibrosis in rat lungs after RAI.

Methods: Fifty female Wistar albino rats were randomly separated into five groups of 10. Group 1 was the control group; Group 2 was administered RAI only; Group 3 was administered RAI and montelukast, Group 4 was administered RAI after total thyroidectomy and Group 5 was administered RAI and montelukast after total thyroidectomy. All rats were sacrificed after 12 weeks and the lungs were evaluated in the histological examination to determine the degree of inflammation and fibrosis and for immunohistochemical (IHC) staining for tissue expression of IL-1, IL-6 and TNF-alpha and TGF-beta.

Results: The RAI-administered groups, Group 2 and Group 4, were significantly different from the control group, however, the groups medicated with both RAI and montelukast, Group 3 and Group 5, were not significantly different from the control group. All histopathological and IHC parameters were significantly less in the groups administered with montelukast compared to the groups not administered with montelukast.

Conclusions: The results of this study demonstrated the radioprotective effect of montelukast in the pulmonary system through histopathological and IHC examination.

Keywords:

• Radioprotectors
• pulmonary damage
• montelukast
• radioactive I131
• radiation fibrosis

Acknowledgments

No sources of public funds or private financial support were used in this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

Arif Osman Tokat

Arif Osman Tokat, M.D., holds a permanent joint appointment as a Professor in the Department of Thoracic Surgery at Bozok University School of Medicine, Erdogan Akdag Research and Application Hospital, Yozgat. He is the founding director of his department. In addition, he had been the founder Director of Ankara Liv Hospital department of Thoracic Surgery in Ankara. Dr Tokat’s research interests include pulmonary carcinoma surgery interventions. He also serves on the editorial boards of numerous medical journals.

Aylin Akbulut

Aylin Akbulut, M.D., works as a Senior Nuclear Medicine Physician at a university hospital. Dr Akbulut’s research interests include radioprotective agents, radioiodine therapy and oncologic imaging with SPECT and PET in small animals. She had post-doc studies in Geneva University Hospital.

Deniz Billur

Deniz Billur, M.D., works as an Associate Professor at Histologist and Embryologist at an University Hospital. Dr Billur’s research interests include morphological changes in small animals and in embryo models.

Gokhan Koca

Gökhan Koca, M.D., works as an Associate Professor at an university hospital. Dr Koca’s research interests include radiosynovectomy and radioprotection in small animal models. He also serves on the editorial boards of numerous medical journals and consults radioprotection committee of the hospital.

Pinar Bayram

Pinar Bayram, M.D., works as a research fellow at Histologist and Embryologist at an university hospital. Dr Bayram’s research interests include genetic expression of apoptosis in animal models.

Serdar Kuru

Serdar Kuru, M.D., holds a permanent joint appointment as an Associate Professor in the Department of General Surgery at an university hospital. Dr Kuru’s research interests include thyroid and abdominal surgery and its effects on animal models. He also performed the total thyroidectomy of our animals in this study.

Sezgin Karasu

Sezgin Karasu, M.D., works as a Senior Thoracic Surgeon at a university hospital. Dr Karasu’s research interests include thoracic surgery in inflammatory pulmonary disease. He also performed the excision of the lungs of our animals in this study together with Dr Tokat and Dr Cakmak.

Suheyla Aydogmus

Suheyla Aydogmus, M.D., works as a Senior Obstetric And Gynecologist at a university hospital. She performed the statistical analysis results of our study.

Hüseyin Cakmak

Hüseyin Cakmak, M.D., works as a Senior Thoracic Surgeon at a private hospital. Dr Cakmak is a famous surgeon with several case series. He also performed the excision of the lungs of our animals in this study together with Dr Tokat and Dr Karasu.

Sengul Ozmert

Dr. Sengul Ozmert, works as a Senior Anesthesiologist at a Training and Research Hospital. Dr Ozmert’s research interests include pediatric anesthesiology. And she also helped us for sedation of our animals.

Meliha Korkmaz

Meliha Korkmaz, M.D., Professor and Director, holds a permanent joint appointment as a Professor in the Department of University Hospital. She is also the founding Director of Nuclear Medicine Department at this hospital. Her research interests include imaging of small animal study models in oncology. She also serves on the editorial boards of numerous medical journals. Dr. Korkmaz received her M.D. degree from Hacettepe University and she had post-doc studies in M.D. Anderson Cancer Center and Ph.D. degrees in Radiopharmacy from Hacetttepe University.