Efficacy of ethane-1-hydroxy-1,1-bisphosphonate (EHBP) for the decorporation of uranium after intramuscular contamination in rats.
OBJECTIVE
To obtain compounds that will effectively reduce the fixation of uranium in its main target organs: bone and kidney. There is an urgent need for a chelating agent that is suitable and available for human use.


METHODS
The efficacy of ethane-1-hydroxy-1,1-bisphosphonate (EHBP), already in use as a therapeutic agent, was investigated in animal experiments. The effect of different treatment regimens was investigated on rats (EHBP: 50-100 micromol kg(-1); ligand/uranium ratio 2500 to 5000).


RESULTS
The present study shows that one prompt injection of EHBP reduced uranium deposition in kidneys by a factor of five after acute intramuscular contamination in rats. At the same time, the total body uranium in the treated animals was 70% of controls. When the treatment was delayed 30 min after contamination, the kidney content was still reduced by a factor of two.


CONCLUSIONS
EHBP has the advantage of clinical acceptance as a therapeutic agent for other purposes and its toxicity has been well studied. It therefore has a role in the treatment of human contamination with uranium.
Henge-Napoli
M H
MH
Institut de Protection et de Sûreté Nucléaire, Département de Protection de la Santé de l'Homme et de Dosimétrie, Service de Dosimétrie, Pierrelatte, France. marie-helene.henge@ipsn.fr
Ansoborlo
E
E
Chazel
V
V
Houpert
P
P
Paquet
F
F
Gourmelon
P
P
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D012968:Etidronic Acid / Q000494:pharmacology*; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014501:Uranium / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine
D000931:Antidotes; D002614:Chelating Agents; D014501:Uranium; D012968:Etidronic Acid