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Diallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit-fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation. [ABSTRACT FROM AUTHOR]

Purpose: Ionizing radiation is known to damage male reproductive system. Current study aims to study the mitigative effects of trichostatin A on male reproductive system and accompanying metabolite changes in testicular tissue of mice. Materials and methods: Eight-week-old male C57 Bl/6J mice were exposed to 2 Gy γ-radiation with or without trichostatin A administration. The animals were sacrificed at various time intervals for organ body weight index, sperm head abnormality assay, sperm mobility assay, and study of various metabolites in testicular tissue using NMR spectroscopy. Results: Ionizing radiation induced no significant change in organ body weight index at any time points studied, however a significant increase in sperm head abnormality and significant decrease in sperm mobility was evident on fifth postirradiation week. trichostatin A administration, 1 and 24 h postirradiation, could efficiently mitigate radiation-induced changes studied. NMR metabolome profile also showed prominent changes associated with energy metabolism, osmolytes and membrane metabolism at 24 h postirradiation and some of these changes (choline, glycerolphosphoethanol amine, and glycine) were persistent till fifth postirradiation week. Trichostatin A administration resulted in reverting metabolic profile of the irradiated animals to normal level suggesting its mitigative role. Conclusion: Results obtained suggest that trichostatin A could restore normal metabolic profile of testicular tissue of irradiated male mice and also restored certain morphological and functional properties of sperms. Trichostatin A thus could further be exploited for its radio-mitigative properties. [ABSTRACT FROM AUTHOR]

Objectives: Preparations of herbal drugs have drawn considerable interest in scientific community in recent years for the treatment of several stress related health problems including radiation-injury. Materials and Methods: An aqueous extract from Valeriana wallichii containing hesperidin as one of its major constituent was evaluated for its ability to protect against radiation-injury in model systems like plasmid deoxyribonucleic acid (DNA) and cultured human fibroblast cells. Results: The extract was found to significantly counter radiation-induced free radicals at 4 h after 5 Gy irradiation, reduced prolonged oxidative stress led increase in mitochondrial mass, enhanced reproductive viability of cultured cells and protected against radiation-induced DNA damage in solution. Discussion: Further studies are required to validate the radioprotective ability of the extract and to develop a safer radioprotective agent. [ABSTRACT FROM AUTHOR]

Radiation damages normal tissues that can adversely affect the success of cancer radiotherapy, safety of nuclear installation workers and military personnel, and public exposed to nuclear accidents. Certain chemicals are able to protect against the harmful effects of radiation. But more than 50 years of research has produced only one approved radioprotective drug, WR-2721 or amifostine. The general utility of WR-2721 is limited by its inherent toxicity and high cost. Efforts to find non-toxic radioprotectors have revealed the promising properties of some medicinal plants. This is an attempt to review the recent publications on radioprotectors and to identify the research needs relevant to developing countries. [ABSTRACT FROM AUTHOR]

AbstractIntravenous and oral 14 d repeated dose toxicity studies of Trichostatin A (TSA) were carried out in Swiss albino mice using low, intermediate, and high doses. Intravenous doses were 10, 25, and 50 μg/kg b.w while the oral doses were 20, 50, and 100 μg/kg b.w. Respective control groups of mice were administered phosphate buffered saline (vehicle only) for 14 consecutive days. All external morphological, hematological, biochemical, urine, histopathological, food intake in addition to body weight and vital organ weight were recorded. During the study no mortality in any animal was observed in either treatment routes. There were no significant changes in morphology, food intake, hematology, biochemical, urine analysis, organ weight. Animals treated high dose of TSA intravenously (50 μg/kg b.w) and orally (100 μg/kg b.w) had enlarged, congested, and discolored kidneys which were statistically significant. Histopathological studies had shown statistically significant degenerated glomerulus in high dose of intravenous and orally treated animals and degenerated tubule were found in orally treated animals. Genotoxicity was evaluated using micronucleus frequency at 14 and 21 d after treatment and chromosomal aberration at 21 d after treatment. Micronucleaus assay and chromosomal assay however did not show any significant changes at any doses and administration routes. Therefore, this study concludes that dose ∼25 µg/kg and ∼50 µg/kg b.w may be considered as No Observed Adverse Effect Level (NOAEL) for intravenous and oral administration of TSA respectively. [ABSTRACT FROM AUTHOR]

A radioprotector, which must be present in the body before irradiation, normally acts as a free radical scavenger, antioxidant and/or inhibits induction of DNA and other macromolecular damages caused by radiation or radiation induced free radical. A radiomitigator on the other hand acts when administered during or shortly after irradiation and therefore it should have properties like repair enhancer of DNA and other macromolecular damages induced by radiation, antiinflammatry properties etc. In the recent past it was hypothesized histone deacetylase (HDAC) inhibitors, widely explored for their anticancer and radiosensitizing properties, can mitigate radiation injury. Our laboratory studied various HDAC inhibitors like trichostatin A (TSA), sulforaphane (SFN), epigallocatechin gallate (EGCG) and diallyl sulfide (DAS) for radiomitigation in cellular and in vivo model systems. Interestingly all those potent and weak dietary HDAC inhibitors exhibited varying degree of radiomitigative potential. Some of the results and the basis of the hypothesis will be discussed extensively. [ABSTRACT FROM AUTHOR]

Radiation countermeasure development has got immense importance owing to the ever expanding application of radiation despite its known detrimental effects. Over last few years, our laboratory has been evaluating some epigenetic modulators, specifically HDAC inhibitors, as radiomitigative agents. The present study investigates the radiomitigative potential of epigallocatechin gallate (EGCG), a polyphenolic extract of green tea. EGCG induces epigenetic changes by altering histone acetylation and DNA methylation status. EGCG was investigated for its radiomitigative effects in vitro conditions using cultured lymphocytes from the blood of healthy individuals. Cultured dishes were irradiated using cobalt teletherapy unit followed by treatment of 100 µm EGCG. Cultured cells were analyzed for their metabolic viability using MTT assay and cell viability using CyQuant dye following 24 and 48h of irradiation and EGCG treatment. Treatment with 100 µm EGCG showed significant increase in cellular viability after 48h of irradiation. Other in vitro parameters were also analyzed such as EGCG significantly reduced the increase in ROS level in 2Gy irradiated cells to almost control level after 2 and 4 h of irradiation, EGCG treatment to 2Gy irradiated cells effectively countered the marginal increase in G2 arrested cells after 48h. Also, there was significant reduction in the total percentage of apoptotic cells in 2Gy irradiated cells following EGCG treatment. These preliminary results suggested the mitigation potential of EGCG against radiation injury. however further detailed molecular studies are required in order to get a better understanding. [ABSTRACT FROM AUTHOR]

Radiation-induced reproductive health disorders have become a major concern in radiotherapy. Trichostatin A (TSA), a fungus (Streptomyces sp.) extract has been a known histone deacetylase inhibitor. In this investigation we hypothesized that Histone Deacetylase inhibitors (HDACi) can minimize radiation-induced apoptosis, genotoxic effects and mitigate radiation injury. However the mitigative mechanism of TSA against radiationinduced mouse testis cell anomalies has not been elucidated yet. Mice were exposed to 2 Gy x-radiation and drug was administered 1 and 24 h post irradiation. Cell viability, sperm head abnormality assay, motility assay and HDAC activity assay were performed for preliminary studies. Apoptosis was examined by the histological examination of testes and studying the expression of apoptotic genes and study of various metabolites in testicular tissue using NMR spectroscopy. In this study the effects of radiation on testis were marked by morphology, motility and viability change, significant rise in apoptotic cells, increased expression of p53. NMR metabolome also showed prominent changes associated with energy metabolites and membrane metabolites at 24h post-irradiation and some of them were retain till 5th week post-irradiation. Interestingly post-irradiation treatment with TSA ameliorated radiation-induced morphology damage and reduced apoptotic cells. Additionally, TSA administration reversed the radiation-induced changes in metabolic profile to normal level. Thus, our results showed that radiomitigative role of TSA on mouse testis were mediated by restoring the normal metabolic profile, morphological and functional properties of sperms. [ABSTRACT FROM AUTHOR]

The small intestine epithelium is highly sensitive to radiation and is the major site of injury during radiation exposure. To examine the role lactobacillus bacteria in HDAC inhibitor DAS mediated radiomitigation of C57BL/6 male mice were used in 4 different groups (a) Radiation alone (7 Gy whole body Co60 gamma irradiation) (b) Drug alone (c) Radiation plus drug (DAS) and (d) control. Bacterial isolation was done from duodenum, jejunum and ileum part of small intestine till 12th after treatment. The intestine was evaluated on the basis of count of lactobacillus count in different part of small intestine, crypt survival and change in expression of TLR2 and TLR5. A significant reduction in lactobacillus microflora was observed in GI tract after exposure to radiation. The damage in villi and crypts were seen. By mitigating the tissue injury, DAS was observed to enhance the count of lactobacillus in GI tract of mice which help in the crypt survival. Lactobacillus also activated the MyD88 (TLR-5), TLR-2 expression in GI tract which help in recovery against radiation injury by reducing epithelial apoptosis. HDAC inhibitor DAS has the potential to increase the lactobacillus count to control GI damage caused by radiation, able to reduce the radiation-induced epithelial injury and improve crypt survival. A TLR-2/MyD88 signaling mechanism leading to activating the immune system seems to operate here. This study raises the possibility that DAS may be useful to limit intestinal injury during radiation therapy. [ABSTRACT FROM AUTHOR]

We assessed the radioprotective and mitigative actions of sodium diclofenac, a non-steroidal anti-inflammatory drug using cultured human peripheral blood as a model. Both pre- and post-irradiation treatments with the drug reduced gamma radiation-induced formation of dicentric chromosome, cytochalasin-blocked micronuclei and γ-H2AX foci in human peripheral blood lymphocytes. This work supports the concept that sodium diclofenac may be a useful radiation countermeasure agent., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Exposure to ionizing radiations, whether medical, occupational or accidental, leads to deleterious biological consequences like mortality or carcinogenesis. It is considered that no dose of ionizing radiation exposure is safe. However, once the accurate absorbed dose is estimated, one can be given appropriate medical care and the severe consequences can be minimized. Though several accurate physical dose estimation modalities exist, it is essential to estimate the absorbed dose in biological system taking into account the individual variation in radiation response, so as to plan suitable medical care. Over the last several decades, lots of efforts have been taken to design a rapid and easy biological dosimeter requiring minimum invasive procedures. The metaphase chromosomal aberration assay in human lymphocytes, though is labor intensive and requires skilled individuals, still remains the gold standard for radiation biodosimetry. The current review aims at discussing the human lymphocyte metaphase chromosomal aberration assay and recent developments involving the application of molecular cytogenetic approaches and other technological advancements to make the assay more authentic and simple to use even in the events of mass radiation casualties.