Nigella Sativa: Protecting the Oral Cavity During X-Irradiation in a Mouse Model

Abstract

Despite advances in radiation delivery, mucositis and xerostomia continue to be debilitating problems for patients undergoing treatment for head and neck cancers. Nigella sativa oil (NSO) is produced from an annual flowering plant that has shown biochemically reproducible and significant cytoprotective properties through anti-inflammatory and anti-oxidant mechanisms when given orally. The goal of this study is to determine whether topical NSO demonstrates radioprotection in oral cavity tissues in mice. Eight-week old, female C3H mice (n=78) are randomly assigned to five groups. They either receive 15 Gy or 18 Gy to the head according to previously established radiation-induced xerostomia and mucositis models. Topical medication, or sham NSO (saline), is administered according to the following schedule: 1mL applied evenly to oral cavity once daily 3 days prior to radiation, 15 minutes prior to radiation on the day of radiation, and then daily for 14 days following radiation. One control group receives topical NSO (without radiation). Endpoints are histopathological changes and weight loss. Weight will be monitored throughout as a measure of food intake, and the mucosal reactions scored daily for signs of inflammation, swelling, ulceration and loss of surface integrity. Subgroups of mice will be sacrificed in intervals starting at day 10 post-irradiation and checked for normal tissue responses including ulceration, reduction in intermolar eminence and salivary gland hypofunction. Histological analyses will be performed on tongue, floor of mouth, buccal mucosa, submandibular gland, and parotid tissues by a single pathologist who will grade radiation tissue damage according to previously described scale. T-tests will be performed to detect significant differences between groups and a P-value <.05 regarded as statistically significant. NSO promises to significantly improve the quality of life of head and neck cancer patients undergoing radiation treatment with and without chemotherapy by alleviating debilitating normal tissue toxicity. Additional studies confirming the therapeutic gain (absence of tumor protection) as well as on optimal timing and dosing are warranted if this trial is successful.