Radiation exposure is relatively easy to detect, but few treatment options exist for people who have already been exposed to high doses.
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From Nature magazine
Two anti-clotting compounds already approved for use in humans may have a surprising role in treating radiation sickness. The findings, reported online today in Nature Medicine, also reveal another avenue for understanding and treating the effects of radiation exposure.
Last year's nuclear accident in Fukushima, Japan, renewed anxiety over the lack of treatments for radiation poisoning. It was long thought that the effects of exposure to high doses of radiation were instantaneous and irreversible, leading to destruction of the gut and loss of bone marrow cells, which damages blood-cell production and the immune system. As a precaution against mass radiation poisoning, many governments stock a treatment called granulocyte colony-stimulating factor. This boosts bone marrow function, but it must be kept refrigerated, has occasional side effects, and must be taken as soon as possible after a disaster has occured.
Hartmut Geiger, a stem-cell biologist at the Cincinnati Children’s Hospital Medical Center in Ohio, and his colleagues have uncovered a therapeutic strategy that can be deployed up to 24 hours after radiation exposure. “Most people think the game is over after you have the damage,” says Geiger. “Now, we know you can modify that.”
The two compounds are thrombomodulin (Solulin/Recomodulin), currently approved in Japan to prevent thrombosis, and activated protein C (Xigris). Xigris, made by pharmaceutical firm Eli Lilly in Indianapolis, Indiana, was a leading drug for treating inflammation from blood poisoning until it was pulled from the US market last October because of a lack of efficacy. In experiments by Geiger and his colleagues, treating mice with either drug led to an eightfold increase in key bone marrow cells needed for the production of white blood cells, and improved the survival rates of mice receiving lethal radiation doses by 40–80%.
Surprise synergy
The radiation study came about when two independent lines of research were united by a chance phone call. Geiger and his colleagues were screening for mutant mice that showed radiation resistance. They noticed that one mutant mouse was particularly resistant, with a mutation that meant it was producing an excess of thrombomodulin.
Meanwhile, a separate team, including physiologist Hartmut Weiler of the Blood Center of Wisconsin in Milwaukee, had been investigating how naturally occurring protein C in the gut would respond to radiation. A mutual colleague connected the two teams after recognizing the seeds of a potentially fruitful collaboration. Thrombomodulin, it turns out, activates protein C. “We talked on the phone, and there was stunned silence after we listened to each other’s data,” says Weiler.
In one key experiment, the researchers exposed 48 mice to 9.5 grays of radiation (a measure of absorbed radiation dose). After 24 hours and 48 hours, 30 mice were injected with activated protein C. After 30 days, only 30% of the uninjected mice had survived, whereas 70% of the injected mice were still alive. Thrombomodulin also increases survival, but must be administered within 30 minutes of radiation exposure to be effective, the researchers found.
“It’s great that the reagents they are using have already been used in humans,” says Mark Whitnall, a radiation biologist at the Armed Forces Radiobiology Research Institute in Bethesda, Maryland. He cautions that the researchers have not conducted the study at the full range of radiation doses as is standard in the field, but he says that it is a great “first stab” and opens up new possibilities for potential drug targets.
The compounds add to a growing arsenal of anti-radiation drugs that are currently being investigated. Last year, researchers at Harvard Medical School in Boston, Massachusetts, identified a potent combination of an antibiotic and a protein that could stave off radiation-induced infections. Whitnall says that two other compounds for treating radiation sickness are due to move forwards into human clinical trials, and that several others have shown promise in animal studies. “It’s been an under-appreciated area,” he says.
This article is reproduced with permission from the magazine Nature. The article was first published on June 25, 2012.
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7 Comments
Add Comment"improved the survival rates of mice receiving lethal radiation doses by 40–80%."
Reply | Report Abuse | Link to thisThe survival rate of mice receiving a lethal radiation dose is, by definition, 0%. If the survival rate increased to anything above 0%, it cannot be said to be a lethal dose. You should clarify what the 40-80% improvement actually means.
Sorry, individual's sizes and reactions vary. A larger human requires a larger dose to reach a fatal dose. Even humans of the same size and weight will vary in effects.
Reply | Report Abuse | Link to thisA lethal dose is the amount required to kill 50% of the recipients.
So 30% survival of untreated mice reflects a slightly more than lethal dose, and 70% survival of treated mice is a great improvement.
If it could take a 10% survival dose and increase this to 20%, that would be just as good in doubling the survival reate.
With the exception of, perhaps, a hundred or so people seriously exposed on the site in the first few days of Chernobyl (some of whom are still alive), and a handful of people exposed in nuclear facilities since the 1950's, there has been very little experience with humans receiving large doses of radiation, and there is likely to be very little in the future. Future cases are probably going to be deliberate poisoning like Alexander Litvinenko, or perhaps from terrorism.
Reply | Report Abuse | Link to thisFar more important would be serious data on the effects of quite small amounts of radiation. Admittedly, not an easy one, but of much more consequence.
Radiation causes red blood cell destruction / hemolysis.
Reply | Report Abuse | Link to this"Radiolysis"
"Radiation-induced haemolysis"
Hemolysis leads to hyperviscous blood.
"Oxidative stress can induce red blood cell rigidity and haemolysis, which in turn can cause hyperviscosity"
Hyperviscous blood leads to thrombosis.
"Hyperviscosity syndrome causes thrombosis and patients are at risk for myocardial infarction and cerebrovascular accidents"
Would the hyperviscous blood be the reason why the anti-clotting compounds work ?
"The standard treatment for thrombosis patients consists of anti-clotting drugs"
A connection : hemolysis and hyperviscosity , and thrombosis / anti-clotting drugs / hyperviscosity ?
If it IS the oxidative stress / hemolysis / hyperviscosity then there is only one logical treatment ? Vitamin E.
Reply | Report Abuse | Link to thisVitamin E is an anti-oxidant which prevents hemolysis , vitamin E deficiency causes hemolysis. Vitamin E has always been considered to be an anti-coagulant , the Dr.'s Shute proved that in the late early sixties.
It has always been considered to be a 'blood thinner' , in fact it is considered to be the 'regulator' as it will either thicken or thin the blood as required.
So one must think the Russians have come up with something over these years with their Chernobyl work ? Does anyone know whether they did any iron reduction , because hemolysis leads to increased iron ? Or did they strictly attempt to attack the oxidation but failed to target the , logically , iron stores which were increased DUE TO the radiation / radiolysis of the red blood cells ?
Is it simply because there is no vitamin E left after a good jolt of radiation ?
Reply | Report Abuse | Link to this"Alpha-tocopherol succinate protects mice from gamma-radiation by induction of granulocyte-colony stimulating factor.
"α-Tocopherol was the most gamma radiation sensitive"
"the role of α-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating the ionizing-radiation-induced gastrointestinal syndrome in mice"
Quote: "Many governments stock a treatment called granulocyte colony-stimulating factor"
Reply | Report Abuse | Link to thisAnswer: "Alpha-tocopherol succinate protects mice from gamma-radiation by induction of granulocyte-colony stimulating factor."
Hmmm ..