Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model

Ana Paola Cotrim, Anastasia L. Sowers, Beatrijs M. Lodde, Joseph M. Vitolo, Albert Kingman, Angelo Russo, James B. Mitchell, Bruce J. Baum

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Abstract

Purpose: Radiotherapy is commonly used to treat the majority of patients with head and neck cancers. Salivary glands in the radiation field are dramatically affected by this procedure. The purpose of this study was to examine pharmacokinetic characteristics of the stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) with respect to radioprotection of the salivary glands. Experimental Dssign: To evaluate the effect of different doses and times of administration, the heads of C3H mice were exposed to a single irradiation dose of 15 Gy, with i.p. tempol injection. To analyze other routes of administration, we injected 275 mg/kg tempol by an i.m., i.v., or s.c. route, 10 minutes before irradiation. We also tested whether oral administration of tempol in a topical form (either in a mouthwash or gel) provided any salivary gland protection. Results: Tempol treatment (137.5 or 275 mg/kg, i.p., 10 minutes before irradiation) significantly reduced irradiation-induced salivary hypofunction (∼50-60%). I.v. or s.c. administration of tempol also showed significant radioprotection, whereas i.m. administration proved to be ineffective. Topical use of tempol, either as a mouthwash or gel, also was radioprotective. Conclusions: Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers.

Original languageEnglish (US)
Pages (from-to)7564-7568
Number of pages5
JournalClinical Cancer Research
Volume11
Issue number20
DOIs
StatePublished - Oct 15 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cotrim, A. P., Sowers, A. L., Lodde, B. M., Vitolo, J. M., Kingman, A., Russo, A., Mitchell, J. B., & Baum, B. J. (2005). Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model. Clinical Cancer Research, 11(20), 7564-7568. https://doi.org/10.1158/1078-0432.CCR-05-0958