1-(2-Hydroxyethoxy) methyl-2-methyl-3-hydroxyl-4-pyridinone: a targeted, bifunctional chelating agent for potential uranic detoxification in the kidney.

The only proposed treatment for uranium (U) internal decontamination is chelation therapy, and so far, there is no effective chelating drug available for this purpose. A modified iron chelator of deferiprone (L1) has been investigated for its chemical and pharmacological properties as a new U chelating agent. The results have demonstrated that the chelator, 1-(2-hydroxyethoxy)methyl-2-methyl-3-hydroxyl-4-pyridinone (HEML1), has the ability to chelate uranyl ion, forming a stable complex with 2:1 (chelator/U) stoichiometry.

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.

Age-associated iron accumulation in bone: implications for postmenopausal osteoporosis and a new target for prevention and treatment by chelation.

Iron accumulation in tissues is believed to be a characteristic of aged humans and a risk factor for some chronic diseases. However, it is not known whether age-associated iron accumulation is part of the pathogenesis of postmenopausal osteoporosis that affects approximately one out three women worldwide. Here, we confirmed that this accumulation of iron was associated with osteopenia in ovariectomized (OVX) rats (a model of peri- and postmenopausal osteoporosis due to estrogen deficiency).

Acyclonucleoside iron chelators of 1-(2-hydroxyethoxy)methyl-2-alkyl-3-hydroxy-4-pyridinones: potential oral iron chelation therapeutics.

The method of synthesizing acyclonucleoside iron chelators is both convenient and cost effective compared to that of synthesizing ribonucleoside iron chelators. The X-ray crystal structural analysis shows that the 2-hydroxyethoxymethyl group does not affect the geometry of the iron chelating sites. Therefore, the iron binding and removal properties of the acyclonucleoside iron chelators should remain similar to the ribonucleoside iron chelators, which is confirmed by the titration and competition reaction of the acyclonucleoside chelators with iron and ferritin, respectively.

An EPR model for separating internal 90Sr doses from external gamma-ray doses in teeth.

The problem of retrospectively measuring radiation doses to humans having both external and internal exposures is addressed. A simplified theoretical model is presented by which the internal exposure from a bone seeking radionuclide can be measured and distinguished from an external gamma-ray dose. The model also provides a means of estimating initial acute uptakes of 90Sr.