Herbal Remedies for Combating Irradiation: a Green Antiirradiation Approach

Plants play important roles in human life not only as suppliers of oxygen but also as a fundamental resource to sustain the human race on this earthly plane. Plants also play a major role in our nutrition by converting energy from the sun during photosynthesis. In addition, plants have been used extensively in traditional medicine since time immemorial. Information in the biomedical literature has indicated that many natural herbs have been investigated for their efficacy against lethal irradiation. Pharmacological studies by various groups of investigators have shown that natural herbs possess significant radioprotective activity. In view of the immense medicinal importance of natural product based radioprotective agents, this review aims at compiling all currently available information on radioprotective agents from medicinal plants and herbs, especially the evaluation methods and mechanisms of action. In this review we particularly emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action and toxicology. We also describe modern techniques for evaluating herbal samples as radioprotective agents. The usage of herbal remedies for combating lethal irradiation is a green antiirradiation approach for the betterment of human beings without high cost, side effects and toxicity

Radioprotective Agents

Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system

Experimental study and evaluation of radioprotective drugs

Experimental study evaluates radioprotective drugs administered before exposure either orally or intravenously. Specifically studied are the sources of radiation, choice of radiation dose, choice of animals, administration of drugs, the toxicity of protective agents and types of protective drug

Some problems and errors in cytogenetic biodosimetry

Human radiosensitivity is a quantitative trait that is generally subject to binomial distribution. Individual radiosensitivity, however, may deviate significantly from the mean (by 2-3 standard deviations). Thus, the same dose of radiation may result in different levels of genotoxic damage (commonly measured as chromosome aberration rates) in different individuals. There is significant genetic component in individual radiosensitivity. It is related to carriership of variant alleles of various single-nucleotide polymorphisms (most of these in genes coding for proteins functioning in DNA damage identification and repair); carriership of different number of alleles producing cumulative effects; amplification of gene copies coding for proteins responsible for radioresistance, mobile genetic elements, and others. Among the other factors influencing individual radioresistance are: radioadaptive response; bystander effect; levels of endogenous substances with radioprotective and antimutagenic properties and environmental factors such as lifestyle and diet, physical activity, psychoemotional state, hormonal state, certain drugs, infections and others. These factors may have radioprotective or sensibilising effects. Apparently, there are too many factors that may significantly modulate the biological effects of ionising radiation. Thus, conventional methodologies for biodosimetry (specifically, cytogenetic methods) may produce significant errors if personal traits that may affect radioresistance are not accounted for

Radioprotective effect of lidocaine on neurotransmitter agonist-induced secretion in irradiated salivary glands.

Previously we verified the radioprotective effect of lidocaine on the function and ultrastructure of salivary glands in rabbits. However, the underlying mechanism of lidocaine's radioprotective effect is unknown. We hypothesized that lidocaine, as a membrane stabilization agent, has a protective effect on intracellular neuroreceptor-mediated signaling and hence can help preserve the secretory function of salivary glands during radiotherapy. Rabbits were irradiated with or without pretreatment with lidocaine before receiving fractionated radiation to a total dose of 35 Gy. Sialoscintigraphy and saliva total protein assay were performed before radiation and 1 week after the last radiation fraction. Isolated salivary gland acini were stimulated with either carbachol or adrenaline. Ca(2+) influx in response to the stimulation with these agonists was measured using laser scanning confocal microscopy. The uptake of activity and the excretion fraction of the parotid glands were significantly reduced after radiation, but lidocaine had a protective effect. Saliva total protein concentration was not altered after radiation. For isolated acini, Ca(2+) influx in response to stimulation with carbachol, but not adrenaline, was impaired after irradiation; lidocaine pretreatment attenuated this effect. Lidocaine has a radioprotective effect on the capacity of muscarinic agonist-induced water secretion in irradiated salivary glands

Could polyphenols really be a good radioprotective strategy?

Currently, radiotherapy is one of the most effective strategies to treat cancer. However, deleterious toxicity against normal cells indicate for the need to selectively protect them. Reactive oxygen and nitrogen species reinforce ionizing radiation cytotoxicity, and compounds able to scavenge these species or enhance antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) should be properly investigated. Antioxidant plant-derived compounds, such as phenols and polyphenols, could represent a valuable alternative to synthetic compounds to be used as radio-protective agents. In fact, their dose-dependent antioxidant/pro-oxidant efficacy could provide a high degree of protection to normal tissues, with little or no protection to tumor cells. The present review provides an update of the current scientific knowledge of polyphenols in pure forms or in plant extracts with good evidence concerning their possible radiomodulating action. Indeed, with few exceptions, to date, the fragmentary data available mostly derive from in vitro studies, which do not find comfort in preclinical and/or clinical studies. On the contrary, when preclinical studies are reported, especially regarding the bioactivity of a plant extract, its chemical composition is not taken into account, avoiding any standardization and compromising data reproducibility

The radioprotective effect of resveratrol against genotoxicity induced by γ-irradiation in mice blood lymphocytes

In this study, we evaluated whether the protective potential of resveratrol (RSV; 3,5,4'-trihydroxy-trans-stilbene) against γ-radiation caused damages in peripheral blood lymphocyte of mice. Resveratrol as a polyphenolic compound scavenges free radicals. Various doses of RSV were administered intraperitoneally 2 hours to adult male mice before a single dose of whole-body γ-irradiation (2 Gy). To assess the protective ability of RSV, the alkaline comet assay in blood lymphocyte of mice was performed and the total comet score was evaluated. The results of the alkaline comet assay showed that RSV significantly inhibited radiationinduced DNA damage. We observed that RSV protects blood lymphocyte against radiation-induced damage in mice

A role of radioprotective agents in cancer therapeutics: a review

In the field of medicine or dentistry, cancer is one of the most common causes for death of the individual worldwide, in which oral cancer accounts for about 10% of it. One of the most important treatment modalities for cancer includes radiotherapy. During radiotherapy, exposure of the normal tissue to these ionizing radiations, results in mutagenesis and cell death. Several modalities and clinical approaches have been made to reduce these early and late complications of the radiotherapies and one among them is, by the means of pharmacological agents. Many experimental and clinical studies have given rise to new concepts of chemical and molecular pharmacological agents that could be effective in protection and treatment of radiation damage to surrounding normal tissues. Clinical Significance: To reduce the significant complications in irradiated patients, the clinical implication of these radioprotective agents have emerged as potential drugs and with anti-tumour effect in the radiotherapy of various cancers including oral carcinomas

Data Mining for Drug Repurposing and New Targets Identification for Radioprotection

Ionising radiation (IR) is responsible for various types of tissue injury leading to morbidity at low doses and mortality at high radiation exposure. Although many radioprotective and pharmacological agents are being tested for decreasing radiation injury, however, the availability of Amifostine as the only clinically used radioprotector with limited indication has prompted us to find out new potential molecules through drugs repurposing for protecting or decreasing radiation damage by data mining. In this work we have used text-mining based network generation approach to find out the gene targets of radioprotectors under evaluation by Agilent Literature Search app in Cytoscape. Extracted genes were evaluated for their association with radiation in Radiation Genes database. These genes were searched against therapeutic drugs and molecules under clinical trial in the Drug Gene Interaction database. We found that most of the radiation target genes were involved in cell death, proliferation, homeostasis, cell cycle and cancer pathways. Many of these genes were druggable and could be targeted by the drugs under clinical research, whereas there were few genes (new targets), which were never considered for radioprotective drug development. This study would likely help in repurposing of identified drugs for use in the event of radiation fallout, keeping in mind that no radiation medical countermeasure for acute radiation syndrome has been approved by the US FDA for use in humans. Results also revealed new target genes for drug targeting and indicates use of similar pipeline in other pathologies for drug repurposing and development

Excellence is the Real Enemy of Practicality! Relevance to Radiation Countermeasure Development

Radiation countermeasures development was undertaken almost six decade ago at AFRRI, USA with the aim to protect military as well as civilian personals against accidental or deliberate radiation exposure. Later on, with the advancement of radiation technologies and exploration of X-ray or γ-rays for diagnostics and therapeutic purposes, probability of radiation exposure was enhanced multifold. Therefore, importance of radiation countermeasures development was recognised globally. However, despite the concentrated efforts, till date not a single FDA approved radio protective drug is available for emergency uses. Major impediments identified in this are included variability in radio protective efficacy with different experimental models, radiation dose rate, radiation types and differential radio sensitivity of various biological systems. No way to evaluate radio protective efficacy of an agent in human volunteers. It is sufficient to realise that uniform excellence may not be achieved in the area of radiation countermeasure development. However, practical excellence based on the radioprotector’s application scenario can be achieved. Different radiation accidental scenarios and feasible practical parameters of excellence for radiation countermeasure development for particular types of incidental, accidental or deliberated radiation exposure are described