ferric-ammonium-citrate and Liver-Neoplasms

Topics: Animals; Antioxidants; Carcinogens; Cells, Cultured; Curcuma; Curcumin; Epithelial Cells; Ferric Compounds; Iron; Iron Overload; Liver; Liver Neoplasms; Oxidative Stress; Plant Extracts; Quaternary Ammonium Compounds; Rats

The recovery from iron overload is hampered by the limited number of pathways and therapeutic agents available for the augmentation of iron secretion/excretion. The present study was aimed to investigate the process of iron storage and release by cultured human hepatoma cells, the role of transferrin receptors and ferritin in this process as well as the effect of iron chelators.. We followed the acquisition, storage and release of iron by cultured cells HepG2 and Hep3B by biochemical means and electron microscopy.. The uptake of iron from diferric transferrin (Trf) was extremely low, while iron as ferric-ammonium-citrate (FAC) was taken up readily, especially by Hep3B cells. Up to 80% of the iron taken up by hepatoma cells was released to the medium. The rate of spontaneous iron release depended on the extent of iron loading. ApoTrf and deferoxamine facilitated release after 1- and 7-day iron-exposure. Up to a third of the radio-iron released from the cells was associated with ferritin. The release of ferritin-iron was not enhanced by either deferoxamine or Trf.. Ferritin-iron release appeared to be an important mechanism of iron discarding in cultured human hepatoma cells, independent of the activity of chelating agents.

Topics: Apoproteins; Carcinoma, Hepatocellular; Culture Media; Deferoxamine; Ferric Compounds; Ferritins; Humans; Iron; Iron Chelating Agents; Iron Overload; Liver Neoplasms; Microscopy, Electron; Quaternary Ammonium Compounds; Receptors, Transferrin; Transferrin; Tumor Cells, Cultured

Hepatic non-transferrin-bound Fe (NTBI) flux and its regulation were characterized by measuring the uptake of Fe from [59Fe]/nitrilotriacetate (NTA) complexes in control and Fe-loaded cultures of human hepatocellular carcinoma cells (HepG2). Exposure to ferric ammonium citrate (FAC) for 1 to 7 days resulted in a time- and dose-dependent increase in the rate of NTBI uptake. In contrast to previous studies showing a dependence of the rate of Fe uptake on extracellular Fe, this was positively correlated with total cellular Fe content. The Fe3+ chelating agents deferoxamine (DFO), 1,2-dimethyl-3-hydroxypyrid-4-one (CP 020) and 1,2-diethyl-3-hydroxypyrid-4-one (CP 094) prevented or diminished the increase in NTBI transport when present during Fe loading and reversed the stimulation in pre-loaded cells in relation to their abilities to decrease intracellular iron. Although saturation of the Fe uptake process was not achieved in control cells, kinetic modelling to include linear diffusion-controlled processes yielded estimated parameters of Km = 4.3 microM and Vmax = 2.6 fmol/micrograms protein/min for the underlying process. There was a significant increase in the apparent Vmax (31.2 fmol/micrograms protein per min) for NTBI uptake in Fe-loaded cells, suggesting that Fe loading increases the number of a rate-limiting carrier site for Fe. Km also increased to 15.2 microM, comparable to values reported when whole liver is perfused with FeSO4. We conclude that HepG2 cells possess a transferrin-independent mechanism of Fe accumulation that responds reversibly to a regulatory intracellular Fe pool.

Topics: Biological Transport; Carcinoma, Hepatocellular; Cell Death; Deferiprone; Deferoxamine; Diffusion; Ferric Compounds; Humans; Iron; Iron Chelating Agents; Iron Radioisotopes; Kinetics; Liver; Liver Neoplasms; Nitrilotriacetic Acid; Pyridones; Quaternary Ammonium Compounds; Transferrin; Tumor Cells, Cultured

Delineation of the gastrointestinal tract in magnetic resonance imaging (MRI) remains a problem. Ferric ammonium citrate is paramagnetic, producing a high MRI signal intensity by virtue of its spin-lattice (T1) relaxation rate enhancement properties. Water is diamagnetic, producing a low MRI signal intensity, especially with short TR and TE times. To compare efficacy for gastrointestinal contrast alteration, ferric ammonium citrate was administered to 18 patients and water was given to 10 patients. Spin-echo imaging at 0.35T was performed after administration of these agents. Ferric ammonium citrate produced high signal intensity within the esophagus, stomach, duodenum, and small intestine that aided in the differentiation of the gastrointestinal tract from adjacent tumors, vessels, and viscera. Delineation of the gut wall was superior using ferric ammonium citrate compared to that produced by water. Delineation of the margins of the pancreas, liver, and kidney from adjacent gastrointestinal tract was also better with ferric ammonium citrate. Optimal distinction between bowel and fat was better with water. Longer TE times (75 to 200 ms) may allow improved contrast between gut and intrabdominal fat using ferric ammonium citrate.

Topics: Adolescent; Adult; Child; Colonic Neoplasms; Contrast Media; Duodenum; Female; Ferric Compounds; Gastrointestinal Diseases; Humans; Iron; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neurofibromatosis 1; Pelvic Neoplasms; Quaternary Ammonium Compounds; Stomach; Water