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Results for “RADIATION PROTECTION”

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PubMed1999

Inhibition of store-operated calcium entry in human lymphocytes by radiation: protection by glutathione.

The influence of gamma radiation on basal compared to activation-dependent Ca(2+) influx in human lymphocytes was investigated. A new quantitative fluorescence technique termed differential ratiometric fluorescence spectroscopy (DRFS) was employed. DRFS facilitated the real-time detection of changes in fluorescence in experimental and control cell samples simultaneously, enabling the resolution of acute moderate changes ( congruent with10-30%) in Ca(2+) (manganese) influx after exposure to ionizing radiation and other oxidant interventions. Exposure to radiation inhibited thapsigargin-stimulated store-operated Ca(2+) influx but not basal Ca(2+) influx in Jurkat T cells and human peripheral blood lymphocytes. The response of store-operated Ca(2+) influx to gamma radiation was dependent on dose between 5 and 40 Gy and was inhibited by preincubation with the Ca(2+) channel blocker Ni(2+), as determined with Jurkat T cells. Elevation of the intracellular concentration of glutathione significantly reduced the inhibition of Ca(2+) influx by gamma radiation. Similar to radiation, both the superoxide anion-generating xanthine/xanthine oxidase system and hydrogen peroxide inhibited thapsigargin-stimulated Ca(2+) influx in Jurkat T cells, and this inhibition was reversed in the presence of the antioxidant N-acetyl-l-cysteine. In conclusion, (1) ionizing radiation inhibited store-operated Ca(2+) entry in human lymphocytes, (2) the sensitivity of Ca(2+) influx to radiation was strictly dependent on depletion of Ca(2+) stores, and (3) glutathione protected against the inhibition of store-operated Ca(2+) entry by gamma radiation.

Acetylcysteine↗
PubMed2005

Radiation protectants: current status and future prospects.

In today's heightened nuclear/biological/chemical threat environment, there is an increased need to have safe and effective means to protect not only special high-risk service groups, but also the general population at large, from the health hazards of unintended ionizing radiation exposures. An unfulfilled dream has been to have a globally effective pharmacologic that could be easily taken orally without any undue side effects prior to a suspected or impending nuclear/radiological event; such an ideal radioprotective agent has yet to be identified, let alone fully developed and approved for human use. No one would argue against the fact that this is problematic and needs to be corrected, but where might the ultimate solution to this difficult problem be found? Without question, representative species of the aminothiol family [e.g., Amifostine (MedImmune, Gaithersburg, Maryland)] have proven to be potent cytoprotectants for normal tissues subjected to irradiation or to radiomimetic chemicals. Although Amifostine is currently used clinically, drug toxicity, limited times of protection, and unfavorable routes of administration, all serve to limit the drug's utility in nonclinical settings. A full range of research and development strategies is being employed currently in the hunt for new safe and effective radioprotectants. These include: (1) large scale screening of new chemical classes or natural products; (2) restructuring/reformulating older protectants with proven efficacies but unwanted toxicities; (3) using nutraceuticals that are only moderately protective but are essentially nontoxic; (4) using low dose combinations of potentially toxic but efficacious agents that protect through different routes to foster radioprotective synergy; and (5) accepting a lower level of drug efficacy in lieu of reduced toxicity, banking on the premise that the protection afforded can be leveraged by post-exposure therapies. Although it is difficult to predict which of these strategies will ultimately prove to be successful, it is certain that the probability of a useful protectant being fielded is increased significantly. This is due to the resurgence of interest in radiation protection, increased resources being expended by federal agencies, and by the Food and Drug Administration's willingness to innovate relative to new approval guidance.

Combinatorial Chemistry Techniques↗