Kinetic studies on the oxidation of oxyhemoglobin by biologically active iron thiosemicarbazone complexes: relevance to iron-chelator-induced methemoglobinemia

Abstract Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borderline iron deficiency, with reductions in spleen and liver iron, but little effect on hemoglobin, hematocrit, transferrin saturation, or plasma iron. Against this backdrop of subclinical iron deficiency, curcumin exerted profound 2 effects on systemic iron, inducing a dose-dependent decline in hematocrit, hemoglobin, serum iron, and transferrin saturation, the appearance of microcytic anisocytotic red blood cells, and decreases in spleen and liver iron content. Curcumin repressed synthesis of hepcidin, a peptide that plays a central role in regulation of systemic iron balance. These results demonstrate that curcumin has the potential to affect systemic iron metabolism, particularly in a setting of subclinical iron deficiency. This may affect the use of curcumin in patients with marginal iron stores or those exhibiting the anemia of cancer and chronic disease.

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A New Pathway for Arachidonic Acid Metabolism in Human Platelets

10.1055/s-0039-1680419 ◽

1977 ◽

Author(s):

S. Rittenhouse-Simmons ◽

F. A. Russell ◽

D. Deykin

Keyword(s):

Arachidonic Acid ◽

Acid Metabolism ◽

De Novo ◽

Platelet Rich Plasma ◽

Gel Filtration ◽

Kinetic Studies ◽

Arachidonic Acid Metabolism ◽

Biologically Active ◽

Resting Cells ◽

Active Metabolites

We are reporting a novel pathway of arachidonic acid metabolism in the phosphatides of thrombin-activated platelets. For kinetic studies of arachidonic acid turnover, platelet phosphatides were labeled by incubation of platelet rich plasma with (3H)-arachidonic acid for 15 min. Unincorporated isotope was removed during subsequent gel-filtration. Platelet phosphatides were resolved and quantitated following two-dimensional silica paper chromatography of chloroform/methanol extracts of incubated platelets. Plasmalogen phosphatidylethanolamine (PPE) was examined on paper chromatograms after its breakdown to lysoPPE with HgCl2. In other experiments, gel-filtered platelets were incubated with (14C)-glycerol to monitor de novo phosphatide synthesis. (3H)-Arachidonic acid was released from phosphatidylcholine and phosphatidylinositol of pre-labeled platelets exposed to thrombin and appeared increasingly in PPE in acyl linkage at glycerol-C-2. (3H)-Arachidonic acid was not found in PPE of resting cells. Maximum transfer occurred with 5 U/ml of thrombin and 15 min, of incubation, with t½ of 2½ min., and was Ca+2 dependent. The presence of aspirin, indomethacin, or eicosatetraynoic acid did not prevent the thrombin-activated transfer of (3H)-arachidonic acid to PPE. The stimulated incorporation of (3H)-arachidonic acid into PPE was not accompanied by a stimulation of (14C)-glycerol uptake into this phosphatide. We suggest that perturbation of the platelet may activate a phospholipase A2 leading to turnover of arachidonic acid in PPE, which is rich in this fatty acid. Such turnover may provide substrate for conversion by cyclo-oxygenase and lipoxydase to biologically active metabolites, and therefore, may offer a locus for regulation of prostaglandin synthesis in the human platelet.

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