Radiation is widely used as an effective therapeutic regimen for treatment of malignancies

Radiation is widely used as an effective therapeutic regimen for treatment of malignancies. But its adverse effects on normal tissues including permanent damages parallel to radiation therapy 1 and limit its effectiveness. Gamma radiation may act directly on component molecules of cells or indirectly causing water radiolysis and further generating free radicals 2. Free radicals interact with adjacent molecules, thereby resulting in DNA damage, oxidation damage and inflammation 2-4. Free radicals-caused peroxidation of lipids leads to structural and functional damage to cellular membranes. Lipid peroxidation, together with DNA damage, constitutes the key events involved in radiation induced cell death.
Inflammation is one of the main responses of the immune system against irritation. Pro-inflammatory cytokines, including TNF-?, IL-6 among others play roles in mediating chronic inflammation and are produced by activated macrophages and CD4+ T cells and mediated by the activation of nuclear factor kappa B (NF?B) 5
NF-?B is an important transcription factor that can be activated in response to a variety of inflammatory stimuli, such as radiation-induced oxidative stress 6. It acts as a redox sensor and has been reported to participate in the activation of radiation-induced inflammatory cascade, Such as tumor necrosis factor alpha (TNF- ?), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the production of nitric oxide (NO) 7,8.
The gastrointestinal (GI) tract is one of the most radiosensitive organs in the body. Radiation exposure damages the intestinal crypts and endocrine glands of the GI tract 9. The possible mortality associated with GI toxicity is believed to be caused by the radiation-induced damage to the intestinal mucosa leading to reduced fluid absorption, electrolyte imbalance, barrier function loss, bacterial translocation, systemic bacterial infection, sepsis, and organ failure 10. This sequence in the GI system is initiated by radiation-induced damage to stem cells that must continually proliferate to maintain crypt integrity and regeneration 11. Crypt cells in the small intestine are susceptible to radiation damage and serve as an indicator of potential survival following total body radiation 12. Early radiation enteropathy occurs during radiotherapy as a result of intestinal crypts cell death, and mucosal inflammation processes 13. Gut toxicity with deep mucosal ulceration appearance with radiotherapy limits the treatment with radiation. 14.
Hence, there is high demand to develop radioprotectors to prevent and/ or ameliorate the side effects of radiation 15 in order to increase survival. Much effort goes to produce these compounds from natural and synthetic sources, with the aim of obtaining derivatives with enhanced biological activities and preparing quantities large enough to allow in-depth pharmacological studies and ultimately clinical applications 16
Chromones (1-benzopyran-4-ones) and chromone derivatives are naturally occurring compounds ubiquitously found in the plant kingdom. Moreover, Chromone chemistry has been widely explored over the past few years, and chromone moiety forms the important component of pharmacophores of a number of biologically active molecules having synthetic or natural origin and many of them have useful medicinal applications 17.
Molecules containing the chromone structure possess a wide spectrum of biological activities such as anti-inflammatory, antimicrobial, antiviral, antitumor and anticancer as well as having the capacity to inhibit several enzymes involved in a wide range of diseases such as oxidoreductase, lipooxygenase and cyclooxygenases 18. They also, display a marked antioxidant capacity which stem from their ability to neutralize active forms of oxygen and to cut off free radical processes 19.
Chromone are growing to be promising agents for use in novel chemotherapeutic strategies, mostly in combination with conventional therapies. Pharmacological and medicinal chemistry outlook has progressively shown that the main benefit of natural and synthetic chromone constituents the capability of exerting chemoprevention as well as therapeutic effects 19.
In the view this, an attempt has been made in this study to demonstrate the possible radioprotective role of the novel designed and synthesized Chromone derivative, with shedding the light on the underlying mechanisms.

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