Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Persistent levels of plasma nontransferrin bound iron (NTBI) have been associated with tissue iron overload and toxicity. We characterized NTBI's susceptibility to deferoxamine (directly chelatable iron [DCI]) and redox activity (labile plasma iron [LPI]) during the course of long-term, continuous L1 (deferiprone) treatment of patients with hemoglobin E disease and beta-thalassemia (n = 17). In 97% of serum samples (n = 267), the LPI levels were more than 0.4 microM (mean +/- SEM, 3.1 +/- 0.2 microM) and the percent transferrin (Tf) saturation more than 85 (111 +/- 6), whereas only in 4% of sera were the LPI levels more than 0.4 microM for Tf saturation less than 85%. Daily administration of L1 (50 mg/kg) for 13 to 17 months caused both LPI and DCI to decrease from respective initial 5.1 +/- 0.5 and 5.4 +/- 0.6 microM to steady mean levels of 2.18 +/- 0.24 and 2.81 +/- 0.14 microM. The steady lowest levels of LPI and DCI were attained after 6 to 8 months, with a half time (t(1/2)) of 2 to 3 months. Serum ferritin and red cell membrane-associated iron followed a similar course but attained steady basal levels only after 10 to 12 months of continuous treatment, with a t(1/2) of 5 to 7 months. These studies indicate that LPI and DCI can serve as early indicators of iron overload and as measures for the effectiveness of iron chelation in reducing potentially toxic iron in the plasma.
 ...
PMID:Labile plasma iron (LPI) as an indicator of chelatable plasma redox activity in iron-overloaded beta-thalassemia/HbE patients treated with an oral chelator. 1515 64

On the basis of all the presented data, one can conclude that oxidative stress plays a major role in the pathophysiology of thalassemia and other congenital and acquired hemolytic anemias. Free extracellular (labile plasma iron, LPI) and intracellular (labile iron pool, LIP) iron species that have been identified in thalassemic blood cells are responsible for generation of oxidative stress by catalyzing formation of oxygen radicals over the antioxidant capacity of the cell. Consequently, there is a rationale for iron chelation to eliminate the free-iron species, which in this respect, act like antioxidants. In addition, antioxidants such as vitamin E and polyphenols are also capable of ameliorating increased oxidative stress parameters and, given together with iron chelators, may provide a substantial improvement in the pathophysiology of hemolytic anemias and particularly in thalassemia.
 ...
PMID:The role of antioxidants and iron chelators in the treatment of oxidative stress in thalassemia. 2071 66