Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy

Kutta, Hannes; Kampen, Uwe; Sagowski, C.; Brenner, Winfried; Bohuslavizki, K. H.; Paulsen, Friedrich

doi:10.1007/s00066-005-1353-3

Cited by 28 publications

(22 citation statements)

References 54 publications

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“…Apoptosis is considered a possible mechanism of SG damage induced by RAI (20). In the present study, TUNEL assays revealed more apoptotic cells in both acini and ducts in RAI-treated mice, indicating that ductal and acinar cells were damaged by RAI.…”

Section: Discussionsupporting

confidence: 57%

“…RAI-treated SGs revealed nonspecific manifestations of cellular injury combined with acinar loss and disorganization, and in some animals, glandular duct enlargement and marked lipomatosis were observed (4,(20)(21)(22). Furthermore, SGs in RAI-treated mice showed pale cytoplasm, atypical ductal configuration, septal widening, lymphocyte infiltration, cytoplasmic vacuolization with pleomorphism, and increasing fibrosis in tissues.…”

Section: Discussionmentioning

confidence: 99%

“…However, this study has some limitations that warrant consideration. First, an RAI dose of 0.01 mCi/g body weight was administered based on a review of related animal studies (0.004-0.0216 mCi/g body weight) (20,(24)(25)(26). According to our preliminary study, this dose appeared to be sufficient to damage SGs without compromising general health.…”

Section: Discussionmentioning

confidence: 99%

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Morphometric and Functional Changes of Salivary Gland Dysfunction After Radioactive Iodine Ablation in a Murine Model

Choi

Park

Kim

et al. 2013

Thyroid

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Background: Ablation of the thyroid tissue using radioactive iodine (RAI) after the surgical removal of welldifferentiated thyroid cancer can induce radiation-related salivary gland (SG) dysfunction. However, in vivo changes of SGs after RAI administration in appropriate animal models are not well described in the literature. This study was undertaken to document morphometric and functional changes during the 12 months after RAI administration in a murine model of RAI-induced SG dysfunction. Methods: Four-week-old female C57BL/6 mice (n = 60) were divided into an RAI-treated group (n = 30) that received RAI orally (0.01 mCi/g body weight) and an unexposed control group (n = 30). Mice in both groups were divided into five subgroups (n = 6 per subgroup) and euthanized at 1, 2, 3, 6, and 12 months post-RAI administration. Salivary flow rates and salivary lag times were measured at 1, 2, 3, 6, and 12 months after RAI administration. Morphological and histological examinations and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were performed. In addition, changes in salivary 99mTc pertechnetate uptake and excretion were observed by single-photon emission computed tomography. Results: In RAI-treated mice, the SGs were significantly lighter than those of unexposed controls at all study time points. Lag times to salivation in the RAI-treated group were greater than in the unexposed controls, but mean salivary flow rates were lower. Histologic examinations of SGs in the RAI group showed pale cytoplasm, atypical ductal configuration, septal widening, cytoplasmic vacuolization with pleomorphism, lymphocyte infiltration, and increased fibrosis. Furthermore, more apoptotic cells were observed in acini and ducts in the RAI group. In addition, patterns of 99m Tc pertechnetate uptake and excretion in the RAI group were quite different from those observed in controls at 1 and 12 months post-RAI. Conclusion: Various histological alterations were observed in mice exposed to RAI, that is, an increase in apoptotic acini and ductal cells and functional SG deterioration. The murine model of RAI-induced SG dysfunction used in the present study appears to be applicable to preclinical research on RAI-induced sialadenitis in patients with well-differentiated thyroid cancer.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Morphometric and Functional Changes of Salivary Gland Dysfunction After Radioactive Iodine Ablation in a Murine Model

Choi

Park

Kim

et al. 2013

Thyroid

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“…The most convincing results are available for a reduction of radiation-induced xerostomia [5,25]. A recent meta-analysis [29] revealed positive effects also for other organs, but nonblinded studies were included.…”

Section: Introductionmentioning

confidence: 99%

Amelioration of Early Radiation Effects in Oral Mucosa (Mouse) by Intravenous or Subcutaneous Administration of Amifostine

Dörr

2006

Strahlenther Onkol

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“…Preclinical studies reported that while amifostine (Ethyol ® ) decreased the level of damage to the parotid gland due to its cytoprotective property, it also protected normal tissues other than the parotid gland against the side effects of RT and chemotherapy (CT). [11][12][13][14][15][16][17][18] Amifostine is a phosphorylated aminothiol (WR2721) prodrug that preferentially accumulates in the salivary gland where it is metabolized to its active form by alkaline phosphatase, WR1065. 19 This active metabolite acts as a free radical scavenger and is considered the effective cytoprotector against side effects of both CT and RT.…”

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confidence: 99%

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

Demiroz¹,

Özkan²,

Cebelli³

et al. 2012

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : We aimed to investigate the effect of amifostine on acute and late side effects, and its tolerability in head and neck cancer patients treated with radiotherapy (RT). M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : The study included 87 patients with primary head and neck cancers and cervical lymph node metastases from unknown primary cancers treated with RT alone or combined with chemotherapy (CT). Forty-one patients (47%) received amifostine combined with RT (ART group) and 46 patients (52%) received RT without amifostine (RT group). The patients were evaluated every week during the treatment and at month 1 and 2 after the completion of RT for acute side effects and month 3, 6, 9, 12, and 24 after the treatment for late side effects according to SOMA/LENT scale. Amifostine was administered prior to RT, along with anti-emetic prophylaxis. The two groups were compared with the Student's t and MannWhitney U and Chi-square tests. R Re es su ul lt ts s: : The ART group had significantly less toxicity (grade 1 mucositis, grade 2 fibrosis) than patients in the RT group (p=0.001, p=0.03, respectively). At week 3 of RT grade 2 mucositis developed in two patients (5%) in the ART group and 10 patients (22%) in the RT group (p=0.02). The protective effect of amifostine on skin reactions developed at week 4 of RT (p=0.05). Grade 3 xerostomia at 9, 12, and 15 months of follow-up (p=0.02, p=0.02, and p=0.02, respectively), grade 2 xerostomia at 18 and 24 months (p=0.02 and p=0.01, respectively) and fibrosis at 15, 18 and 24 months (p=0.05, p=0.02 and p=0.02, respectively) decreased markedly in the ART group compared with the RT group. Emesis was the most common adverse effect of amifostine. C Co on nc cl lu us si io on n: : Daily administration of amifostine during RT was effective in avoiding late grade 2-3 xerostomia, as well as grade 2 fibrosis. K Ke ey y W Wo or rd ds s: : Radiotherapy; head and neck cancer; amifostine; xerostomia Ö ÖZ ZE ET T A Am ma aç ç: : Amifostinin radyoterapi (RT) ile tedavi edilmiş baş ve boyun kanseri hastalarında akut ve geç yan etkiler üzerindeki etkisini ve tolerabilitesini araştırmayı amaçladık. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmaya, tek başına RT veya RT ve eş zamanlı kemoterapi (KT) ile tedavi edilmiş primer baş ve boyun kanseri olan ve primeri bilinmeyen bir kanserden servikal lenf düğümlerine metastaz yapmış 87 hasta dâhil edildi. Kırk bir hastaya (47%) RT ile birlikte amifostin (ART grup) ve 46 hastaya (52%) amifostin olmaksızın RT (RT grubu) verildi. Olgular, tedavi sırasında akut yan etkiler açısından her hafta ve RT bittikten sonra 1. ve 2. ayda, geç yan etkiler açısından ise tedavi bittikten sonra 3., 6., 9., 12., ve 24. aylarda SOMA/LENT skalasına göre değerlendirildiler. Amifostin RT'den önce antiemetik profilaksi ile beraber uygulandı. İki grubun, komplikasyonlar üzerindeki etki açısından karşılaştırılmasında Student-t ve Mann Whitney-u testleri kullanıldı. B Bu ul lg gu ul la ar r: : AR...

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Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy

Abstract: The results indicate that parenchymal damage in salivary glands induced by high-dose radioiodine therapy can significantly be reduced by amifostine. Therefore, amifostine therapy may increase quality of life in patients with differentiated thyroid cancer after radioiodine treatment.

Cited by 28 publications

References 54 publications

Morphometric and Functional Changes of Salivary Gland Dysfunction After Radioactive Iodine Ablation in a Murine Model

Morphometric and Functional Changes of Salivary Gland Dysfunction After Radioactive Iodine Ablation in a Murine Model

Amelioration of Early Radiation Effects in Oral Mucosa (Mouse) by Intravenous or Subcutaneous Administration of Amifostine

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

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