Radiation therapy following surgery is a standard treatment modality applied in the head and neck cancers . Even, at later stages of cancer, due to the inoperable conditions radiotherapy may become the only option . Although in conjunction with surgery radiotherapy offers high rates of cure, but may induce complications like nausea, vomiting, weight loss, myelosuppression, and mucositis , . Oral mucositis is one of the most common complications and develops in approximately 80% of patients who receive radiation therapy for head and neck cancers . Oral mucositis, is a dysfunction whose nature, duration and severity cannot be determined exactly, and it varies depending on the treatment method and the patient . However, hospitalization rates due to mucositis lesions were reported up to 16%. Seventy percent of patients with grade 3–4 radiation-induced mucositis (RIOM) in need of feeding tube insertion .
Oral mucosa constitutes of rapidly proliferating cells. Hereby, mucositis usually develops 2–3 days after initiating radiotherapy. In general, the lesions are frequently observed in the non-keratinized buccal mucosa, anterior part of the tongue and areas such as the floor of the mouth, but can also be seen in keratinized areas like the dorsum of tongue , . While erythema, mild pain and taste sensation alterations are observed around 20 Gy in conventional fractionated radiotherapy (in 1–2 weeks); At 30–40 Gy, patchy mucositis, pseudomembrane formation, severe pain and ulceration are observed . In the later stages, symptoms like deep inflamed ulcerations and hemorrhage may accompany RIOM . Also, the addition of concurrent chemotherapy regime, accelerated fractionation and hyperfractionation applications increase the incidence and severity of mucositis . Nevertheless, the long term prognosis of RIOM is considered good due to self-limiting nature. Usually, the RIOM recess within 2–4 weeks following the cessation of radiotherapy . However, the lesions may prevent or complicates the usual course of radiotherapy from various aspects, such as radiation dose alterations, and changes in dose fractionation. Besides, RIOM poses risks for the patient's systemic health, such as malnutrition, dehydration, and prolonged hospitalization for total parenteral nutrition .
The pathophysiology of RIOM remains unclear. Recently, some studies proposed a pathogenesis constitute of four phases. Due to the hypothesis, initially an inflammatory phase initiates by radiotherapy induced tissue damage, and damage causes the release of inflammatory cytokines such as interleukin (IL)-1β, prostoglandins, and tumor necrosis factor-α (TNF-α) . Although RIOM is a self-limiting disorder, it could be a fatal damage in moderately to severely ill patients in which RIOM mandates cessation of radiotherapy and even intensive care admission. Also, patient losses may become inevitable in such cases .
In 2020, MASC/ISOO systematically reviewed the treatment modalities for RIOM and grouped under 8 headings in the clinical practice guideline . One of these headings is natural and miscellaneous agents. Propolis, one of the products evaluated under the title, and it was stated that new evidence was identified but more data is needed for recommendation , . Propolis is an adhesive, dark-colored resin formed by honey bees use in the hive for various purposes, composed by the mixture of the products they collect from plants and their saliva. Anti-inflammatory, antioxidant, antibacterial, antiviral, antifungal, immunomodulatory, and antimutagenic effects of propolis have been demonstrated , . Propolis reveals its anti-inflammatory effects by restraining prostoglandin synthesis, promoting the phagocytic capacity of immune cells, inducing cellular immunity, and improving the healing capacity of epithelial tissues .
Considering the pathobiology of RIOM, the current experimental animal study was designed to investigate the suppressive effects of propolis on pro-inflammatory cytokines and apoptosis that occur in primary damage and ulcerative phases, and possible positive effects on healing of lesions. The primary aim of the study is to examine the effects of propolis on inflammation in the buccal mucosa, which is one of the areas with the most RIOM observed, and the secondary aim is to examine its effects on biochemical changes in the affected tissue.