An Evaluation of Potent Radioprotective Effect of Dimethyl Sulfoxide for Acute Radiation-Induced Lung Injury: Tc99m-DTPA Transalveolar Clearance Scintigraphy Correlated by Histopathologic Findings

Year 2022, Volume: 9 Issue: 3, 266 - 272, 30.12.2022

Bengu Depboylu

https://doi.org/10.47572/muskutd.1076492

Abstract

This study aims to investigate the radioprotective effects of dimethyl sulfoxide in the acute phase of radiation-induced lung injury by technetium-99m-diethylenetriaminepentaacetic acid transalveolar clearance scintigraphy in a rabbit model. Twenty white New Zealand rabbits were grouped as (1) control, (2) sham irradiation, (3) irradiation plus dimethyl sulfoxide, and (4) dimethyl sulfoxide alone. Right hemithorax regions of the rabbits in the sham irradiation and irradiation plus dimethyl sulfoxide groups were irradiated with a single dose of 20 Gy by a Cobalt60 treatment unit. Dimethyl sulfoxide (4.5 gr/kg) was administered intraperitoneally, 30 minutes before irradiation. The technetium-99m-diethylenetriaminepentaacetic acid transalveolar clearance scintigraphy was performed on the 14th day after irradiation. The rabbits were sacrificed on the 15th day, and both lungs were removed for histopathologic evaluation. Administration of dimethyl sulfoxide before irradiation caused a marked prolongation in the transalveolar clearance rate of diethylenetriaminepentaacetic acid through the alveolocapillary membrane (p=0.028), protected the anatomic ultrastructure of the lung parenchyma, markedly decreased the severity of exudate in the alveoli in histopathologic evaluation. Our study results showed that dimethyl sulfoxide has safely eliminated inflammatory response induced by irradiation while not causing any negative alterations in the structure of the normal lung tissue and preserving the integrity of the alveolocapillary membrane, especially in the acute phase. Dimethyl sulfoxide appears to be a safe and well-tolerated protective agent for the prevention of RILI. Technetium-99m-diethylenetriaminepentaacetic acid transalveolar clearance scintigraphy is accepted as a cheap, easily reproducible, sensitive assay to monitor radiation toxicity reactions in acute RILI.

Keywords

dimethyl sulfoxide, radioprotective agent, radiation-induced acute lung injury, transalveolar clearance scintigraphy, radioprotector

Supporting Institution

Trakya Üniversitesi

Project Number

Protokol Numarası: TUTFEK-2007/83

Thanks

The author extends her gratitude to Prof. Dr. Zafer Koçak for his mentorship during the study.

Akut Radyasyona Bağlı Akciğer Hasarlanmalarında Dimetil Sülfoksitin Radyokoruyucu Etkisinin Tc99m-DTPA Transalveolar Klirens Sintigrafisi ve Histopatolojik Bulgularla Araştırılması

Abstract

Bu çalışma, bir tavşan modelinde teknesyum-99m-dietilentriaminpentaasetik asit transalveolar klirens sintigrafisi ile radyasyona bağlı akciğer hasarının akut fazında dimetil sülfoksitin radyoprotektif etkilerini araştırmayı amaçlamaktadır. Yirmi beyaz Yeni Zelanda tavşanı (1) kontrol, (2) ışınlama, (3) ışınlama artı dimetil sülfoksit ve (4) tek başına dimetil sülfoksit şeklinde gruplandırıldı. Işınlama ve ışınlama artı dimetil sülfoksit gruplarındaki tavşanların sağ hemitoraks bölgeleri Cobalt60 tedavi ünitesi ile tek doz 20 Gy ışınlandı. Işınlamadan 30 dakika önce intraperitoneal yolla dimetil sülfoksit (4.5 gr/kg) uygulandı. Teknesyum-99m-dietilentriaminpentaasetik asit transalveolar klirens sintigrafisi ışınlamadan sonraki 14. günde yapıldı. Tavşanlar 15. günde sakrifiye edildi ve histopatolojik değerlendirme için her iki akciğer çıkarıldı. Işınlamadan önce dimetil sülfoksitin uygulanması, histopatolojik değerlendirmede dietilentriaminpentaasetik asidin alveolokapiller membrandan transalveolar klirens hızında belirgin bir uzamaya neden oldu (p=0.028), akciğer parankiminin anatomik yapısını korudu, alveollerdeki eksüda şiddetini belirgin şekilde azalttı (p=0.042). Çalışma sonuçlarımız, dimetil sülfoksitin, normal akciğer dokusunun yapısında olumsuz bir değişikliğe neden olmadan ve özellikle akut fazda alveolokapiller membranın bütünlüğünü koruyarak, ışınlamaya bağlı inflamatuar yanıtı güvenli bir şekilde ortadan kaldırdığını göstermiştir. Dimetil sülfoksit, RILI'nin önlenmesi için güvenli ve iyi tolere edilen bir koruyucu ajan gibi görünmektedir. Teknesyum-99m-dietilentriaminpentaasetik asit transalveolar klirens sintigrafisi, akut RILI'de radyasyon toksisitesini izlemek için ucuz, kolay tekrarlanabilir, hassas bir test olarak kabul edilmektedir.

Keywords

dimetil sülfoksit, radyoprotektif ajan, radyasyona bağlı akut akciğer hasarı, transalveolar klirens sintigrafisi, radyoprotektör

Project Number

Protokol Numarası: TUTFEK-2007/83

References

• 1. Abratt RP, Morgan GW, Silvestri G, et al. Lung toxicity following chest irradiation in patients with lung cancer. Lung Cancer. 2002;35:103-9.
• 2. Shepherd AF, Iocolano M, Leeman J, et al. Clinical and Dosimetric Predictors of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation Therapy Pract Radiat Oncol. 2021;11(1): 52-62.
• 3. Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21(1):109-22.
• 4. Rodrigues G, Lock M, D’Souza D, et al. Prediction of radiation pneumonitis by dose - volume histogram parameters in lung cancer--a systematic review. Radiother Oncol. 2004;71(2):127-38.
• 5. Bledsoe TJ, Nath SK, Decker RH. Radiation Pneumonitis. Clin Chest Med. 2017 ;38(2):201-8.
• 6. Schallenkamp JM, Miller RC, Brinkmann DH, et al. Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates. Int J Radiat Oncol Biol Phys. 2007;67(2):410-6.
• 7. Vogelius IR, Bentzen SM. A literature-based meta-analysis of clinical risk factors for development of radiation induced pneumonitis. Acta Oncol. 2012;51(8):975-83.
• 8. Palma DA, Senan S, Tsujino K, et al. Predicting radiation pneumonitis after hemoradiation therapy for lung cancer: An international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2013;85:444-50.
• 9. Lee YH, Kim YS, Lee SN, et al. Interstitial Lung Change in Pre-radiation Therapy Computed Tomography Is a Risk Factor for Severe Radiation Pneumonitis. Cancer Res Treat. 2015;47(4):676-86.
• 10. Xia C, Shi W, Zhang Y, et al. Prevention and treatment of radiation-induced lung injury. Future Med Chem. 2020;12(23):2161-73.
• 11. Vujaskovic Z, Feng QF, Rabbani ZN, et al. Assessment of the protective effect of amifostine on radiation-induced pulmonary toxicity. Exp Lung Res. 2002;28(7):577-90.
• 12. Bourhis J, Blanchard P, Maillard E, et al. Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol. 2011;29(18):2590-7.
• 13. Calveley VL, Jelveh S, Langan A, et al. Genistein can mitigate the effect of radiation on rat lung tissue. Radiat Res. 2010;173(5):602-11.
• 14. Day RM, Barshishat-Kupper M, Mog SR, et al. Genistein protects against biomarkers of delayed lung sequelae in mice surviving high-dose total body irradiation. J Radiat Res. 2008;49(4):361-72.
• 15. Giuranno L, Ient J, De Ruysscher D, et al. Radiation-Induced Lung Injury (RILI). Front Oncol. 2019;9:877.
• 16. Ozturk B, Egehan I, Atavci S, et al. Pentoxifylline in prevention of radiation-induced lung toxicity in patients with breast and lung cancer: a double-blind randomized trial. Int J Radiat Oncol Biol Phys. 2004;58(1):213-9.
• 17. Prasanna PG, Stone HB, Wong RS, et al. Normal tissue protection for improving radiotherapy: where are the gaps? Transl Cancer Res. 2012;1:35-48.
• 18. Koukourakis MI. Radiation damage and radioprotectants: new concepts in the era of molecular medicine. Br J Radiol. 2012; 85:313-30.
• 19. Leake CD, Rosenbaum EE, Jacob SW. Summary of the New York Academy of Sciences symposium on the “biological actions of dimethyl sulfoxide”. Ann N Y Acad Sci. 1967;141(1):670-1.
• 20. Highman B, Hansell JR, White DC. Radioprotective effect of dimethyl sulfoxide in rats. Radiat Res. 1967;30(3):563-8.
• 21. Brayton CF. Dimethyl sulfoxide (DMSO): a review. Cornell Vet. 1986;76(1):61-90.
• 22. Kashino G, Liu Y, Suzuki M, et al. An alternative mechanism for radioprotection by dimethyl sulfoxide; possible facilitation of DNA double-strand break repair. J Radiat Res. 2010;51(6):733-40.
• 23. Galvao J, Davis B, Tilley M, et al. Unexpected low-dose toxicity of the universal solvent DMSO. FASEB J. 2014;28(3):1317-30.
• 24. Petković VD, Keta OD, Vidosavljević MZ, et al. Biological outcomes of γ-radiation induced DNA damages in breast and lung cancer cells pretreated with free radical scavengers. Int J Radiat Biol. 2019;95(3):274-85.
• 25. Osterreicher J, Pejchal J, Skopek J, et al. Role of type II pneumocytes in pathogenesis of radiation pneumonitis: dose response of radiation-induced lung changes in the transient high vascular permeability period. Exp Toxicol Pathol. 2004;56(3):181-7.
• 26. Abid SH, Malhotra V, Perry MC. Radiation-induced and chemotherapy-induced pulmonary injury. Curr Opin Oncol. 2001;13(4):242-8.
• 27. Suga K, Alderson PO, Mitra A, et al. Early retardation of 99mTc-DTPA radioaerosol transalveolar clearance in irradiated canine lung. J Nucl Med. 2001;42(2):292-9.
• 28. McDonald S, Rubin P, Chang AY,et al. Pulmonary changes induced by combined mouse beta-interferon (rMuIFN-beta) and irradiation in normal mice--toxic versus protective effects. Radiother Oncol. 1993;26(3):212-8.
• 29. Johnston CJ, Piedboeuf B, Rubin P, et al. Early and persistent alterations in the expression of interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor alpha mRNA levels in fibrosis-resistant and sensitive mice after thoracic irradiation. Radiat Res. 1996;145(6):762-7.
• 30. Uzal C, Durmus-Altun G, Caloglu M, et al. The protective effect of amifostine on radiation-induced acute pulmonary toxicity: detection by (99m) Tc-DTPA transalveolar clearances. Int J Radiat Oncol Biol Phys. 2004;60(2):564-9.
• 31. Redlich CA, Rockwell S, Chung JS, et al. Vitamin A inhibits radiation-induced pneumonitis in rats. J Nutr. 1998;128(10):1661-4.
• 32. Susskind H, Weber DA, Lau YH, et al. Impaired permeability in radiation-induced lung injury detected by technetium-99m-DTPA lung clearance. J Nucl Med. 1997;38(6):966-71
• 33. Atkins HL, Weber DA, Susskind H, et al. MIRD dose estimate report no. 16: radiation absorbed dose from technetium-99m-diethylenetriaminepentaacetic acid aerosol. J Nucl Med. 1992;33(9):1717-9.
• 34. O’Doherty MJ, Peters AM. Pulmonary technetium-99m diethylene triamine penta-acetic acid aerosol clearance as an index of lung injury. Eur J Nucl Med. 1997;24(1):81-7.
• 35. Ahmed IH, el-Khatib E, Logus JW, et al. Altered pulmonary epithelial permeability in canine radiation lung injury. J Appl Physiol (1985). 1986;61(3):971-81.
• 36. Jackson IL, Xu P, Hadley C, et al. A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule. Health Phys. 2012;103(4):463-73.
• 37. Gross NJ. Radiation pneumonitis in mice. Some effects of corticosteroids on mortality and pulmonary physiology. J Clin Invest. 1980;66(3):504-10.
• 38. Käsmann L, Dietrich A, Staab-Weijnitz CA, et al. Radiation-induced lung toxicity - cellular and molecular mechanisms of pathogenesis, management, and literature review. Radiat Oncol. 2020;15(1):214.
• 39. Ashwood-Smith MJ. Current concepts concerning radioprotective and cryoprotective properties of dimethyl sulfoxide in cellular systems. Ann N Y Acad Sci. 1975;243:246-56.
• 40. Peng R, Zhang W, Zuo Z, 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.
• 41. Raaphorst GP, Azzam EI. Fixation of radiation-induced potentially lethal damage by anisotonic treatment and its modification by DMSO or BrdUrd in V79 cells. Radiat Environ Biophys. 1985;24(3):175-84.
• 42. Chen HH, Jia RF, Yu L, et al. Bystander effects induced by continuous low-dose-rate 125I seeds potentiate the killing action of irradiation on human lung cancer cells in vitro. Int J Radiat Oncol Biol Phys. 2008;72(5):1560-6.
• 43. Neklasova NIu, Sharinov GM, Vinokurov VL, et al. Local application of dimethyl sulfoxide at different concentrations to the prevention of radiation-induced damages in patient with cancer of the cervix uteri. Vestn Rentgenol Radiol. 2006;(3):47-51.
• 44. Zharinov GM, Vershinina SF, Dran’kova OI. Profilaktika luchevykh povrezhdeniĭ mochevogo puzyria i priamoĭ kishki s pomoshch’iu lokal’nogo primeneniia dimetilsul’foksida [Prevention of radiation damage to the bladder and rectum using local application of dimethyl sulfoxide]. Med Radiol (Mosk). 1985;30(3):16-8.
• 45. Vinokurov VL, Zharinov GM, Stoliarova IV, et al. Rezultaty modifitsirovannoĭ luchevoĭ terapii bolńykh rakom matki [Results of modified radiotherapy in the treatment of patients with uterine cancer]. Vestn Rentgenol Radiol. 1993;(5):55-7
• 46. Zúñiga A, Burdach R, Rubio S. Dimethyl sulfoxide therapy in bronchiolitis. Ann N Y Acad Sci. 1975;243:460-7.
• 47. Scott, AH. Respiratory Problems. In Scott AH, The DMSO Handbook for Doctors. 2013; 104-106. iUniverse, LLC; Bloomington-USA.