Targeting of Inflammation for Radiation Protection and Mitigation

Abstract

So far, various targets have been proposed for the amelioration of radiation toxicity in radiotherapy. Of different targets, NF-κB, COX-2, some of NADPH Oxidase subfamilies, TGF-β, p38 and the renin-angiotensin system have shown promising results. Interestingly, inhibition of these targets can help sensitize the tumor cells to the radiation treatment with some mechanisms such as suppression of angiogenesis and tumor growth as well as induction of apoptosis. In this review, we focus on recent advances on promising studies for targeting the inflammatory mediators in radiotherapy.

Metformin modulates cardiac endothelial dysfunction, oxidative stress and inflammation in irradiated rats: A new perspective of an antidiabetic drug

“…showed that treatment of mice with metformin before or 24 h after exposure to irradiation mitigated the damaging effects of radiation . So far, some radioprotectors such as melatonin and hesperidin ameliorate heart damage induced by ionizing radiation due to their ability to improve infiltration of immune cells including macrophages, lymphocytes and mast cells . Together, these findings further support the notion that, antioxidants lessen cardiac enzymes activities in serum due to its free radicals scavenging effect .…”

“…This raised the impetus to search for an effective radioprotective agent that can help to mitigate several side effects in normal tissues through targeting free radicals, inflammatory cytokines and mediators as well as remove the pro‐inflammatory mediators from the damaged area, thus preventing the development of chronic inflammation and subsequent damage to tissues …”

Radiation Protection and Mitigation by Natural Antioxidants and Flavonoids: Implications to Radiotherapy and Radiation Disasters

“…Using another inhibitor of TGF-βR1 (LY2109761) 4 weeks after a single irradiation of the thorax with 20 Gy showed mitigation of lung inflammation and fibrosis [68]. Other studies have shown that targeting of proinflammatory and pro-fibrotic mediators can mitigate severe inflammation and fibrosis in the heart and lung, leading to an increase in survival [69][70][71][72][73].…”

Randomized, double‐blind, placebo‐controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy

“…Radiation triggers different cellular signaling pathways that lead to activation of proinflammatory cytokines and thus development of inflammatory responses (Dent et al, ; Farhood et al, ; Najafi et al, ; Stone, Coleman, Anscher, & McBride, ). Targeting of inflammation for radioprotection is a remarkable approach (Farhood et al, ; Kalman et al, ; Yahyapour et al, ). Cellular and molecular mechanisms by which the curcumin exerts its radioprotective effects are thought to be inhibition of nuclear factor‐κB signaling pathway, reducing expression of inflammatory factors and DNA damage, scavenging the free radicals, and enhancing the expression of antioxidant enzymes (Ak & Gulcin, ; Biswas, McClure, Jimenez, Megson, & Rahman, ; Iqbal, Sharma, Okazaki, Fujisawa, & Okada, ; Nishinaka et al, ; Shi et al, ).…”