Therapeutic effects of an oral chelator targeting skeletal tissue damage in experimental postmenopausal osteoporosis in rats.
Earlier studies revealed that age-associated iron accumulation plays an important causal role in osteopenic development after estrogen deficiency. It is believed that an increase in iron content is associated with an increased likelihood of oxidative damage at the point of iron accumulation. However, there is no direct evidence that the iron accumulated in skeletal tissue causes free radical oxidative damage and consequent bone loss. Iron depletion from skeletal tissues of ovariectomized (OVX) rats was carried out with the oral chelator [1-N-docosyl-triethylenetetraminepentaacetic acid (DoTTPA)]. Results suggest the causal role of iron in oxidative damage that may lead to bone loss in the rats. The results also show the therapeutic potential of the bone-targeted chelator to protect against bone loss associated with age-iron accumulation as well as iron overload diseases.
Liu
Gang
G
Radiobiology Division, Department of Radiology, School of Medicine, University of Utah, Salt Lake City, Utah 84108, USA. gang.liu@m.cc.utah.edu
Men
Ping
P
Kenner
Gerry H
GH
Miller
Scott C
SC
D000085:Acetates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism / Q000627:therapeutic use*; D018482:Muscle, Skeletal / Q000378:metabolism*; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism* / Q000517:prevention & control*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014266:Trientine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D000085:Acetates; D005609:Free Radicals; D007502:Iron Chelating Agents; C076893:docosyl-triethylenetetraminepentaacetic acid; D007501:Iron; D014266:Trientine