Iron translocation by free fatty acids

Our plain-English summary of Iron translocation by free fatty acids, by M.W. Qian, J.W. Eaton (The American Journal of Pathology, 1991).

The study

• Authors: M.W. Qian, J.W. Eaton
• Journal: The American Journal of Pathology
• Published: 1991;139(6):1425-34
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Organic extracts of cigarette smoke and uncombusted tobacco contain substances capable of translocating iron from aqueous solutions into immiscible organic solvents. Such extracts will also effect the organic solvation of iron present in ferruginous forms of asbestos such as amosite and crocidolite (Qian and Eaton, Arch Biochem Biophys 1989, 275:280). These substances, previously detected by their iron-translocating properties, have now been purified and identified by mass spectroscopy as saturated fatty acids, predominantly stearic and palmitic acids. Organic extracts of tobacco smoke, as well as the pure fatty acids, also transfer ferrous iron into both isolated red cell membranes and intact human erythrocytes. The increased membrane iron may enhance cellular susceptibility to exogenous oxidants; erythrocyte membranes subject to fatty acid-mediated iron accumulation show elevated peroxidation of endogenous polyunsaturated fatty acids. These observations may help explain the phlogistic effects of tobacco use and suggest, in a broader context, that free fatty acids may act as physiologic and pathologic mediators of metal translocation.

In plain English

This laboratory study sought the iron-moving substances in cigarette smoke. The authors' earlier work had found that smoke extracts could pull iron out of iron-rich asbestos such as crocidolite and amosite. No asbestos was tested in this article. From Camel nonfilter cigarette smoke, the authors purified the iron-moving material, and mass spectroscopy identified it as the saturated fatty acids stearic and palmitic acids. Separate gas chromatography confirmed both and also found a smaller amount of oleic acid. Normal human red blood cells incubated with added iron plus smoke extract or pure palmitic acid took up iron. Adding fat-free albumin, which binds fatty acids, blocked this. Fatty acids shorter than 12 to 14 carbons worked poorly. Red cell membranes given iron and rising amounts of palmitic acid, then challenged with ascorbate and hydrogen peroxide, showed progressively more oxidation of their fats. The authors concluded that this may help explain inflammatory effects of smoke, particularly in smokers exposed to asbestos. They noted that any role of smoke-borne fatty acids in smoke's chromosome-damaging and cancer-promoting effects is not known.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on cigarette smoke extracts, pure fatty acids, human red blood cells and red cell membranes
• Who was studied: Chloroform extracts of smoke from Camel nonfilter cigarettes, plus normal human red blood cells and isolated red cell membranes taken from venous blood (number of donors not reported), at the University of Minnesota
• Exposure: Smoke condensate and pure free fatty acids (including stearic, palmitic and oleic acids, and palmitic acid methyl ester), combined with ferrous iron. No asbestos was tested in this article. The asbestos link (smoke extracts leaching iron from crocidolite and amosite) comes from the authors' earlier 1989 study.
• Main results:
  • Mass spectroscopy of the purified iron-translocating fraction of smoke condensate (which held more than 70% of the activity) matched stearic and palmitic acids. Only the highest-molecular-weight fatty acid was definitely resolved by this method. Separate gas chromatography confirmed both, along with a lesser amount (less than 10% of total) of oleic acid.
  • Reagent stearic acid, like smoke condensate, moved ferrous iron from water into chloroform.
  • Human red cells were incubated with 100 micromolar added ferrous sulfate plus smoke condensate or pure palmitic acid (80 micromolar). These cells accumulated iron and differed from all other samples at P less than 0.01. Adding fatty acid-free bovine serum albumin blocked the uptake.
  • Four patterns held both for moving iron into chloroform and for moving it into red cells. The best fatty acid to iron ratio was about 2:1. Fatty acids shorter than 12 to 14 carbons were relatively ineffective. Palmitic acid methyl ester had no activity. Oleic acid was as effective as stearic and palmitic acids.
  • Red cell membranes were exposed to 10 micromolar iron and increasing concentrations of palmitic acid, then challenged with sodium ascorbate and hydrogen peroxide. They showed progressively greater lipid peroxidation, measured as thiobarbituric acid reactive substances.
  • The greatest increase in membrane fat oxidation came with saturated fatty acids of 14 to 18 carbons. The palmitic acid (16:0) methyl ester had no effect.
• The authors' conclusion: The authors concluded that most of the iron-moving activity in tobacco products is due to palmitic and stearic acids. They suggested that this may help explain the proinflammatory and clastogenic (chromosome-damaging) effects of smoke constituents, particularly those observed in smokers exposed to asbestos.
• Limitations the authors state:
  • The authors have no definitive structure for the presumed complex of iron and saturated fatty acid.
  • Normal body levels of calcium and magnesium may reduce fatty acid-driven iron uptake by cells, to an unknown extent.
  • Saturated fatty acids give identical mass spectroscopy fragmentation patterns, so only the heaviest (284 daltons) was definitely resolved. Separate gas chromatography was used to confirm stearic and palmitic acids.
  • The extent of involvement, if any, of smoke-borne fatty acids in the clastogenic and cocarcinogenic effects of smoke constituents is not known.

Topics

Medical terms in this study, explained in our Lexicon: Translocation, Amosite, Crocidolite.

Related studies

• Free fatty acids inhibit protein tyrosine phosphatase 1B and activate Akt — E. Shibata, T. Kanno, et al. (2013)
• Tobacco-borne siderophoric activity — M.W. Qian, J.W. Eaton (1989)
• Free radical generation at the solid/liquid interface in iron containing minerals — B. Fubini, L. Mollo, et al. (1995)
• Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors — P.S. Gilmour, D.M. Brown, et al. (1997)
• Free radical generation in the toxicity of inhaled mineral particles: the role of iron speciation at the surface of asbestos and silica — I. Fenoglio, L. Prandi, et al. (2001)
• Iron mobilization from asbestos by chelators and ascorbic acid — L.G. Lund, A.E. Aust (1990)

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