Modification of iron uptake and lipid peroxidation by hypoxia, ascorbic acid, and alpha-tocopherol in iron-loaded rat myocardial cell cultures.
The ability of ascorbic acid, alpha-tocopherol, and hypoxia to modify iron uptake, chelation, and toxicity as manifested by the generation of malonyldialdehyde (MDA) was studied in myocardial cell cultures obtained from newborn rats. Exposure to 20 micrograms/ml iron provided as 59Fe-ferric ammonium citrate in serum-free Ham F-10 culture medium resulted in the accumulation of 39% of the iron within 24 hours and a 10- to 12-fold increase in cellular MDA. Hypoxia (1% oxygen) resulted in a more than twofold increase in iron uptake but only minor changes in cellular MDA concentrations. Ascorbic acid and alpha-tocopherol (1 mg/ml) had opposing effects on iron uptake and MDA production. Ascorbic acid reduced 24-hour iron uptake by 73% (P less than 0.001) whereas alpha-tocopherol increased iron uptake by 19% (P less than 0.025). In contrast, cellular MDA after iron loading increased by 86% with the addition of ascorbate, and was reduced by 75% with alpha-tocopherol (P less than 0.001). The ratio of increase in cellular MDA relative to percent iron uptake (lipid peroxidation ratio) was 7.29 with iron loading plus ascorbate vs. 0.13 with iron loading plus alpha-tocopherol, a 56-fold difference between the two extremes. In vitro deferoxamine treatment for 3 hours resulted in a 53% reduction in the radioactive iron content of iron-loaded heart cells and a 40% reduction in MDA. Simultaneous deferoxamine and ascorbate or alpha-tocopherol treatment did not affect iron mobilization, but had a profound effect on MDA concentrations. Ascorbic acid prevented entirely the beneficial effect of deferoxamine on MDA concentrations in iron-loaded cells, whereas alpha-tocopherol potentiated the effect of deferoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D000860:Hypoxia / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008314:Malonates / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D014810:Vitamin E / Q000494:pharmacology*
D008054:Lipid Peroxides; D008314:Malonates; D014810:Vitamin E; D008315:Malondialdehyde; D007501:Iron; D001205:Ascorbic Acid