Current Molecular Pharmacology   Send Orders for Reprints to reprints@benthamscience.ae Current Molecular Pharmacology, 2018, 11, 203-210 203 REVIEW ARTICLE Targeting of Inflammation for Radiation Protection and Mitigation Rasoul Yahyapour 1 , Peyman Amini 2 , Saeed Rezapoor 2 , Abolhasan Rezaeyan 3 , Bagher Farhood 4 , Mohsen Cheki 5 , Hengameh Fallah 6 and Masoud Najafi 7,* 1 School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran; 2 Department of Radiology, faculty of paramedical, Tehran University of Medical Sciences, Tehran, Iran; 3 Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; 4 Departments of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran; 5 Department of Radiolog- ic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 6 Department of Chemistry, Islamic Azad University of Arak, Arak, Iran and 7 Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Iran Abstract: Background: Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mu- cositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on. Discussion: Observations have proposed that inflammatory mediators are involved in the toxic effect of ion- izing radiation on non-irradiated cells via a phenomenon named bystander effect. Inflammation in both irra- diated and non-irradiated cells can trigger genomic instability, leading to increased risk of carcinogenesis. Targeting the inflammatory mediators has been an interesting idea for improving the therapeutic ratio throughout the reduction of normal tissue injury as well as an increase in tumor response to radiotherapy. Conclusion: 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 tar- gets can help sensitize the tumor cells to the radiation treatment with some mechanisms such as sup- pression 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. A R T I C L E H I S T O R Y Received: September 28, 2017 Revised: October 27, 2017 Accepted: October 30, 2017 DOI: 10.2174/1874467210666171108165641 Keywords: Inflammation, Radiation, Radioprotection, COX-2, NF-κB, gastrointestinal toxicity, mucositis, angiogenesis. 1. INTRODUCTION Inflammation is an immunological response that guards the body against several harmful stimuli such as foreign bac- teria or endogenous alarms. Moreover, inflammatory re- sponses trigger the recovery process in the damaged area. The inflammation process is very complicated which engag- es a wide change in genes expression, enzymes activity, im- mune cell migration (including macrophage and T lympho- cyte cells), and others [1]. These changes are associated with the release of several types of inflammatory cytokines, reac- tive oxygen species (ROS) and nitric oxide (NO) [2]. In a normal situation, acute inflammation following exposure to a *Address correspondence to this author at the Radiology and Nuclear Medi- cine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Iran; E-mail: masoudnajafi67@yahoo.com stimulus such as ionizing radiation must be terminated by anti-inflammatory mechanisms that remove the pro- inflammatory components from the damaged area. This mechanism prevents the development of chronic inflamma- tion and subsequent damages to tissues. Yet, in some situa- tions like exposure to a high dose of ionizing radiation may lead to a massive cell damage, which causes long-term im- mune responses [3]. In this situation, continuous oxidative stress and inflammation can result in disruption of the nor- mal function of cells [4]. Moreover, chronic ROS production induced by inflammation after exposure to radiation plays a key role in genomic instability and carcinogenesis [5]. According to detrimental effects of inflammatory re- sponses during or after radiotherapy or a radiation accident, management of inflammation can help to mitigate several side effects in normal tissues [6]. Several targets including inflammatory cytokines and mediators, and free radicals are 1874-4702/18 $58.00+.00 © 2018 Bentham Science Publishers Personal Use Only Not for Distribution