Pharmacological Protection From Radiation 卤 Cisplatin-Induced Oral Mucositis

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• 作者：Ana P. Cotrim ; D.D.S. ; Ph.D.^&lowast ; ; ¹ ; Masanobu Yoshikawa ; Ph.D.^&lowast ; ; ^&dagger ; ; ¹ ; Abraham N. Sunshine ; B.S.^&lowast ; ; Changyu Zheng ; M.D. ; Ph.D.^&lowast ; ; Anastasia L. Sowers ; A.A.S.^&Dagger ; ; Angela D. Thetford ; C.L.A.T.^&Dagger ; ; John A. Cook ; Ph.D.^&Dagger ; ; James B. Mitchell ; Ph.D.^&Dagger ; ; Bruce J. Baum ; D.M.D. ; Ph.D.^&lowast ; ; ^{bbaum@dir.nidcr.nih.gov}
• 关键词：Chemoradiation ; Side effects ; Oral mucositis ; Tempol ; D-methionine
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2012
• 期刊代码：136_03603016
• 类别：med
• 出版时间：15 July, 2012
• 卷：83
• 期：4
• 页码：1284-1290
• 文件大小：586 K

摘要

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Purpose

To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation 卤 cisplatin.

Methods and Materials

Female C3H mice, 鈭? weeks old, were irradiated with five fractionated doses 卤 cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured.

Results

Significant lingual ulcers resulted from 5 脳 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection.

Conclusions

Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.