Radioprotective Agents: Strategies and Translational Advances

Abstract

Radioprotectors are agents required to protect biological system exposed to radiation, either naturally or through radiation leakage, and they protect normal cells from radiation injury in cancer patients undergoing radiotherapy. It is imperative to study radioprotectors and their mechanism of action comprehensively, looking at their potential therapeutic applications. This review intimately chronicles the rich intellectual, pharmacological story of natural and synthetic radioprotectors. A continuous effort is going on by researchers to develop clinically promising radioprotective agents. In this article, for the first time we have discussed the impact of radioprotectors on different signaling pathways in cells, which will create a basis for scientific community working in this area to develop novel molecules with better therapeutic efficacy. The bright future of exceptionally noncytotoxic derivatives of bisbenzimidazoles is also described as radiomodulators. Amifostine, an effective radioprotectant, has been approved by the FDA for limited clinical use. However, due to its adverse side effects, it is not routinely used clinically. Recently, CBLB502 and several analog of a peptide are under clinical trial and showed high success against radiotherapy in cancer. This article reviews the different types of radioprotective agents with emphasis on the strategies for the development of novel radioprotectors for drug development. In addition, direction for future strategies relevant to the development of radioprotectors is also addressed.

Overview of Radiation-protective Agent Research and Prospects for the Future

“…84) The increased understanding of drug interaction with biological signaling and metabolic networks will be needed if we intend to improve the therapeutic index of novel radioprotective agents. Even if the acute radiation injury is avoided by these drugs, drugs should be developed such that they can also avoid long-term adverse effects such as carcinogenic and leukemia.…”

Histopathological efficiency of amifostine in radiation‑induced heart disease in rats

“…Amifostine holds its radioprotective actions by several indirect mechanisms, particularly it scavenges radiation-induced free radicals, repairs the chemical damage by donating hydrogen atoms, and induces intracellular hypoxia by auto-oxidation (5). Additionally, amifostine may also act as a radioprotector by its direct actions on cells by arresting the cell cycle at G1 phase and inducing p21 expression (6). There are few articles in literature investigating the protective effect of amifostine on RIHD (7,8).…”

Protection of Radiation induced Somatic Damage by the Reduction of Oxidative Stress at Critical Organs of Rat with Naringenin Administration

“…Amifostine (WR-2721) is a U.S. FDA approved effective radioprotector which is a phosphorothioate (Hall & Giaccia 2006). However, the clinical use of Amifostine is limited due to the severe side effects such as nausea, vomiting, hypotension, nephronand neuro-toxicity (Kamran et al 2016). Therefore, the studies on new naturally occurring compounds from plants or fruits have been fulfilled for the development of safe radioprotector which is less toxic and more effective.…”