Modification of iron uptake and lipid peroxidation by hypoxia, ascorbic acid, and α-tocopherol in iron-loaded rat myocardial cell cultures

C. Hershko*, G. Link, A. Pinson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

The ability of ascorbic acid, α-tocopherol, and hypoxia to modify iron uptake, chelatlon, and toxicity as manifested by the generation of malonyldialdehyde (MDA) was studied in myocardial cell cultures obtained from newborn rats. Exposure to 20 μg/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 α-tocopherol (1 mg/ml) had opposing effects on iron uptake and MDA production. Ascorbic acid reduced 24-hour iron uptake by 73% (P < 0.001) whereas α-tocopherol increased iron uptake by 19% (P < 0.025). In contrast, cellular MDA after iron loading increased by 86% with the addition of ascorbate, and was reduced by 75% with α-tocopherol (P < 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 α-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 α-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 α-tocopherol potentiated the effect of deferoxamine. These observations may be pertinent to the aggravating effect of coexistent hypoxia on the severity of myocardial iron accumulation and the possible aggravation of myocardial damage by ascorbate therapy, and underline the need to explore the therapeutic potential of α-tocopherol in protecting tissues from the harmful effects of iron excess.

Original languageAmerican English
Pages (from-to)355-361
Number of pages7
JournalTranslational Research
Volume110
Issue number3
StatePublished - Sep 1987

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