Evaluation of the Effect of Nigella Sativa for the Prophylaxis to Radiation Induced Dermatitis in Breast Cancer Patients

Radiation induced dermatitis (RID) is one of the most commonly reported adverse events of breast radiation therapy (RT).Radiation therapy toxicity is exhibited within hours to weeks of exposure and persisting throughout the course of treatment. Radiation induced dermatitis is a result of generation of reactive oxygen species (ROSs), which in return induces epidermal and dermal inflammatory responses. Radiation causes structural tissue damage, which trigger production of pro-inflammatory mediators; as NF-κB, iNOS, COX-2, EGFR, MCP-1, and cytokines such as IL-1, IL-2, IL-6, TNF-a, and IFN- γ, and immune-stimulatory response; involving an increased movement of leukocytes from the blood into the irradiated tissues. Subsequently erythema, ulceration, and edema are developed. This is then followed by thinning of the epidermis, accompanied with degeneration of glands, which manifests as dry desquamation. If damage to the basal cells and glands is more severe, moist desquamation occur. From previous, it can be deduced that inflammatory response plays a significant role in the radiotherapy induced dermatitis.

There are many agents that are used in the management of RID in the clinical settings, however, up till now there is none supported by the guidelines. Radiation induced dermatitis occurrence, not only could it impair the patient's quality of life but it could also affect the RT course of treatment, which could negatively influence the cancer treatment. Therefore more effort is needed to find a method of prevention of RID, resulting from breast RT, especially that there is no standard of care for prophylaxis to the radiation induced dermatitis (RID).

Nigella sativa is herbal medicine that has been widely used in different parts of the world by different cultures. It has been used traditionally as a remedy for several diseases including fever, cough, chronic headache, dizziness, back pain, dysmenorrhea, obesity, diabetes, infection and inflammation, hypertension, and gastrointestinal disorders such as flatulence, and dysentery. Preclinical and clinical studies have demonstrated the anti-inflammatory, immunomodulatory, antioxidant, analgesic, and antimicrobial properties of N. sativa.

Thymoquinone (TQ) is the prominent constituent of Nigella sativa, to which the biological properties have been attributed. Thymoquinone can act as a potent free radical and superoxide radical scavenger at both nanomolar and micromolar range, respectively. As well as, its beneficial effects on antioxidant enzymes, and its detrimental effects on pro-inflammatory mediators/cytokines, and pro-inflammatory transcription factor; nuclear factor kappa B (NF-κB).

Based on literature, Nigella sativa has been shown to have antioxidant and anti-inflammatory effects. As, both the fixed oil of N. sativa, as well as thymoquinone (the main compound of the essential oil), were proven to inhibit non-enzymatic lipid peroxidation and have an appreciable free radical scavenging properties. Furthermore, orally administered Nigella sativa oil showed a reduction of IL-4 and NO production in rats. Additionally, Thymoquinone showed anti-inflammatory activity through inhibition of cyclooxygenase (COX) and 5-lipooxygenase (5-LPO), as well as through lowering TNF-α and IL-1β levels in arthritis in rats. It is worth mentioning that thymoquinone was proven to significantly reduce pancreatic ductal adenocarcinoma cell synthesis of MCP-1, TNF-a, IL-1β and Cox-2. It also inhibited the constitutive and TNF-a-mediated activation of NF-kB.