Effect of Tempol on the prevention of irradiation-induced mucositis in miniature pigs.
OBJECTIVE
The goals of this study were to (i) establish a useful miniature pig (minipig) model for irradiation-induced oral mucositis and (ii) evaluate the effect of Tempol to prevent its development.


METHODS
Minipigs were irradiated with 6 Gy for five consecutive days targeting the entire oral cavity. To prevent radiation damage, minipigs were treated with 30 mg kg-1Tempol 10 min before irradiation (n = 4), while the radiation-alone group was similarly injected with saline (n = 4). Lesions were graded using an oral mucositis score and visual inspection every 3 days, and biopsy of multiple sites was performed at day 18. Weight and chest and abdominal circumferences were measured every 3 days.


RESULTS
Lesions began about 12 days after the first irradiation fraction and healed about 30 days after irradiation. Epithelial thickness was calculated on the lingual and buccal mucosa on the 18th day after the first irradiation fraction. Tempol provided modest protection from ulceration after irradiation using this treatment strategy.


CONCLUSIONS
This study established a useful large animal model for irradiation-induced oral mucositis and showed modest beneficial effects of Tempol in limiting tissue damage. The latter finding may be potentially valuable in preventing oral mucositis in patients receiving irradiation for head and neck cancers.
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
L
L
Hu
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
Y
Y
Wang
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
A P
AP
Cotrim
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
Z
Z
Zhu
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
R
R
Gao
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
C
C
Zheng
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
C M
CM
Goldsmith
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
L
L
Jin
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
C
C
Zhang
Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
J B
JB
Mitchell
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
B J
BJ
Baum
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.|Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, China.
S
http://orcid.org/0000-0002-7066-2654
S
Wang
D000818:Animals; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011878:Radiotherapy / Q000009:adverse effects; D013113:Spin Labels; D013280:Stomatitis / Q000517:prevention & control*; D013552:Swine
D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D013113:Spin Labels; C001803:tempol
Tempol; fractionated irradiation; minipig; oral mucositis