Modification of radiation-induced acute oral mucositis in the rat.
OBJECTIVE
A new non-toxic drug (compound A) consisting of curcumin, alpha-tocopherol and sunflower oil was developed and its efficacy tested in the treatment of radiation-induced oral mucositis in the rat.


METHODS
Mature (12 weeks old, 200-225 g) female Sprague-Dawley rats were used. While under general anaesthesia, the tongues of the animals were slightly extended outside and a region of the underside of the tongue was irradiated in-situ with single doses of 2.27 MeV beta-rays from a 5-mm diameter 90Sr/90Y plaque. The dose-rate of the source was about 10 Gy min(-1) at the surface of the mucus membrane. Irradiations and subsequent assessment of the lesion were carried out under general anaesthesia maintained by a 1.5% halothane/oxygen mixture. Six groups of animals were irradiated with single doses of 13.5, 15.0, 16.5 or 18Gy. One subgroup (radiation only) received no further treatment, while the other five groups received 0.5 ml day(-1) of either compound A, sunflower oil, alpha-tocopherol, curcumin or water containing 10% ethanol by oral gavage until the end of experiments. Mucosal ulceration (erosion of mucosal epithelium) was considered as an end-point. From the day after irradiation until any acute radiation-induced oral mucosal lesion had healed, the tongues of the animals were assessed daily for the presence of radiation-induced mucositis (mucosal ulceration). Quantal data for the incidence of radiation-induced mucositis were analysed using logit analysis and a dose-modification factor was obtained.


RESULTS
There was a modest increase in ED50, the dose expected to cause mucositis in 50% of the animals after both alpha-tocopherol and sunflower oil were administered. This resulted in dose-modification factors of 1.05. While curcumin treatment resulted in a dose-modification factor of 1.09. Compound A significantly reduced the incidence of radiation-induced mucositis with a statistically significant dose-modification factor of 1.2 +/- 0.1.


CONCLUSIONS
Curcumin and other components of compound A appeared to be effective in the prevention of radiation-induced oral mucositis. However, the overall effect observed with the combination drug (compound A) appeared greater than additive.
Rezvani
M
M
Research Institute (University of Oxford), Churchill Hospital, Oxford OX3 7LJ, UK. mohi.rezvani@resin.ox.ac.uk
Ross
G A
GA
D000818:Animals; D003474:Curcumin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D009061:Mouth Mucosa / Q000473:pathology* / Q000528:radiation effects*; D019226:Oral Ulcer / Q000209:etiology*; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074242:Sunflower Oil; D014059:Tongue / Q000473:pathology / Q000528:radiation effects; D014456:Ulcer / Q000209:etiology; D024502:alpha-Tocopherol / Q000494:pharmacology
D010938:Plant Oils; D000074242:Sunflower Oil; D000431:Ethanol; D024502:alpha-Tocopherol; D003474:Curcumin