Appraisal of biochemical classes of radioprotectors: evidence, current status and guidelines for future development

Abstract

The search for efficient radioprotective agents to protect from radiation-induced toxicity, due to planned or accidental radiation exposure, is still ongoing worldwide. Despite decades of research and development of widely different biochemical classes of natural and derivative compounds, a safe and effective radioprotector is largely unmet. In this comprehensive review, we evaluated the evidence for the radioprotective performance of classical thiols, vitamins, minerals, dietary antioxidants, phytochemicals, botanical and bacterial preparations, DNA-binding agents, cytokines, and chelators including adaptogens. Where radioprotection was demonstrated, the compounds have shown moderate dose modifying factors ranging from 1.1 to 2.7. To date, only few compounds found way to clinic with limited margin of dose prescription due to side effects. Most of these compounds (amifostine, filgratism, pegfilgrastim, sargramostim, palifermin, recombinant salmonella flagellin, Prussian blue, potassium iodide) act primarily via scavenging of free radicals, modulation of oxidative stress, signal transduction, cell proliferation or enhance radionuclide elimination. However, the gain in radioprotection remains hampered with low margin of tolerance. Future development of more effective radioprotectors requires an appropriate nontoxic compound, a model system and biomarkers of radiation exposure. These are important to test the effectiveness of radioprotection on physiological tissues during radiotherapy and field application in cases of nuclear eventualities.

The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells

“…Despite many advances in supportive care, the toxicities of chemotherapy and radiotherapy still limit their efficacy, utility and acceptability to patients and clinicians, and result in poor quality of life for patients, treatment-related deaths and inadequate outcomes [ 19 ]. Apart from antiemetics and haemopoietic growth factors, few agents substantially prevent these toxicities, many are poorly-tolerated, and some reduce toxicities while compromising anticancer efficacy [ 20 , 21 , 22 ]. In contrast, Se compounds offer the potential, at optimum doses, of being well-tolerated agents that can improve both cancer outcomes and treatment toxicities.…”

Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro

“…Oxidative stress, nitro-oxidative stress and mitochondrial impairment are often noted as possible factors in the etiology of cisplatin-induced neuronal injury (Areti et al 2014 ; Carozzi et al 2010 ; Ma et al 2018 ; Maj et al 2017 ; Waseem et al 2018 ). Many different agents have been tested as possible interventions (Albers et al 2014 ; Avan et al 2015 ; Freyer et al 2017 ; Fu et al 2017 ; Glimelius et al 2018 ; Kerckhove et al 2017 ; Mishra and Alsbeih 2017 ; Piccolo and Kolesar 2014 ; Schloss et al 2013 ), but a clear view of their mechanism of action is still lacking. In this work, several small molecules (histidine, sodium azide and WR1065) and proteins (SOD and catalase) were tested as possible modulators of cisplatin effects on differentiated, non-dividing neurons in cell culture.…”

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

“…The radioprotective property of a large number of agents has been studied but, disappointingly, hardly any drug has so far entered into clinical practice (Hosseinimehr, ; Mishra & Alsbeih, ). Previous trials have shown that different routes of amifostine administration (i.e., intravenous, intrarectal, and subcutaneous) can reduce the incidence and severity of radiation‐induced rectal toxicity in patients undergoing pelvic RT; however, several amifostine‐related toxicities were also reported in these studies (Dunst, Semlin, Pigorsch, Muller, & Reese, ; Koukourakis et al, ; Koukourakis et al, ; Kouloulias et al, ; Kouvaris et al, ).…”