Radiation Countermeasures: Current Status

Abstract

Deleterious effects of ionising radiation leading to significant morbidity and mortality have been studied elaborately. A range of synthetic, semisynthetic and herbal compounds have been screened as radiation countermeasure agents and a number of promising radiation countermeasure agents are under development. Amifostin is the only drug which has been approved by the United State Food and Drug Administration (US-FDA), but that too for use in a defined population under strict medical supervision. Granulocyte Colony Stimulating Factor/filgrastim, γ-tocotrienol, genistein are at an advanced stage of development and are tested on higher animal models as per required norms of FDA. Herbal compounds are also considered very safe and of high value as radiation countermeasure agents owing to various properties like antioxidant, immunomodulation activity etc. Histone deacetylase inhibitors such as Trichostatin A, Diallyl sulphide, Sulforaphane are being viewed as very promising radiomitigating agents by our laboratory and active research in the same direction is going on. Infusion of hematopoietic stem cells and growth factors are in practice as potent therapeutics. This review gives an overview on various radioprotectors, radiomitigators and therapeutic agents either available or under development currently.

Herbal Radioprotectors: A mini-review of the Current Status

“…Since last six decades, extensive efforts have been done in the area of radiation biology to develop synthetic radioprotector with minimal toxicity. Various compounds including cytoprotective agents, immuno-modulators, cytokines, vitamins and many DNA binding compounds have been evaluated for their radioprotective potential both in animal models and in vitro conditions (Haritwal et al, 2017). Synthetic sulfhydryl compounds like cysteine, mercaptoethylamine, cystine gained significant attention but their high toxicity and other side effects like nausea, vomiting, hypotension limited their use necessitating the search for other compounds with minimal toxicity and more acceptability (Maisin, 1989).…”

Radiation-Induced Epigenetic Changes And Their Modulation By Epidrugs

“…Research in the field of epidrugs discovery has been promoted on account of the important role of epigenetic dysregulation in the development and progression of tumor. Accordingly, several types of epidrugs have been studied against radiationinduced damages (Haritwal 2017).…”

“…Currently, there are various HDACi under research for their radioprotective and mitigative activity such as Trichostatin A (TSA), Diallyl sulfide (DAS), Sulforaphane, and Epigallocatechin-3-gallate (EGCG) (Haritwal 2019). EGCG administration HDACi increase histone acetylation of genes which further enhances the repair proteins to DNA ultimately increasing the DNA repair (Haritwal 2017). TSA, a highly potent HDACi, has shown promising results against radiation injuries in testes evidenced by structural and functional changes in mice testes and spermatogenesis (Haritwal 2019).…”

Radiation Injury: Mechanism of Toxicity and Countermeasures

“…Radiations countermeasures are used to modify radiation-induced alterations and have been classified into three groups: Radio-protectors, Radio-mitigators and Radio-therapeutics (Figure 4). 25 They are grouped based on the time of drug delivery concerning the irradiation and mode of action. An ideal radio countermeasure should have few properties like protection against the damages by both chronic and acute irradiation, easy oral administration with the property of rapid absorption and distribution throughout the body with no undue or toxic side effects, even behavioural.…”

“…31,32 More radioprotective compounds are being developed and under investigation like Palifermin, ALXN4100TPO, Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte Monocyte-Colony Stimulating Factor (GM-CSF), γ-tocotrienol, Manganese Superoxide Dismutase (MnSOD, also called SOD2). 25 Apart from that various natural products have been investigated as radioprotector agents because of excellent antioxidant, antimicrobial, anti-inflammatory activity with no evidence of toxicity. Moreover, herbal agents can also scavenge reactive nitrogen and free radicals thus protecting the cell from the adverse effect of irradiation.…”