title: Pharmacological protection from radiation ± cisplatin-induced oral mucositis.
abstract: OBJECTIVE
  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 ± cisplatin.
  
  
  METHODS
  Female C3H mice, ∼8 weeks old, were irradiated with five fractionated doses ± 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 × 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.
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-1190, USA.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Cotrim
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Abraham N
authors.initials: AN
authors.lastname: Sunshine
authors.forename: Changyu
authors.initials: C
authors.lastname: Zheng
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Sowers
authors.forename: Angela D
authors.initials: AD
authors.lastname: Thetford
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Baum
mesh_terms: D000818:Animals; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D005260:Female; D008715:Methionine / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects*; D013113:Spin Labels; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D013113:Spin Labels; D008715:Methionine; D002945:Cisplatin; C001803:tempol