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


METHODS
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 (approximately 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.
Cotrim
Ana P
AP
Gene Therapy and Therapeutics Branch and Biostatistics Core, Division of Clinical Research and Health Promotion, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA. acotrim@nidcr.nih.gov
Sowers
Anastasia L
AL
Lodde
Beatrijs M
BM
Vitolo
Joseph M
JM
Kingman
Albert
A
Russo
Angelo
A
Mitchell
James B
JB
Baum
Bruce J
BJ
D000818:Animals; D016371:Cranial Irradiation / Q000009:adverse effects*; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004333:Drug Administration Routes; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D051379:Mice; D008809:Mice, Inbred C3H; D023421:Models, Animal; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012469:Salivary Glands / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012472:Salivation / Q000187:drug effects / Q000528:radiation effects; D013113:Spin Labels; D014987:Xerostomia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*
D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D013113:Spin Labels; C001803:tempol