The effects of caffeic acid and its related catechols on hydroxyl radical formation by 3-hydroxyanthranilic acid, ferric chloride, and hydrogen peroxide
Iwahashi H, Ishii T, Sugata R, Kido R
Department of Chemistry, Wakayama Medical College, Japan.
Arch Biochem Biophys 1990 Jan;276(1):242-7
The effect of caffeic acid on hydroxyl radical formation through a reaction, which contained 0.22 M carbonate buffer (pH 7.4), 0.22 mM 3-hydroxyanthranilic acid, 87 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), 2.9 mM hydrogen peroxide, and 14 microM FeCl3, was investigated. The addition of 30 microM caffeic acid resulted in the decrease of hydroxyl radical formation in the reaction mixture. Chlorogenic acid, 3,4-dihydroxy-phenylalanine noradrenaline, gallic acid, dopamine, epicatechin, and D-(+)-catechin also suppressed the hydroxyl radical formation. In regard to the positional isomers of benzenediol, o-benzenediol inhibited the hydroxyl radical formation, but m- and p-benzenediol did not. The inhibitory effect of the hydroxyl radical formation seems to be due to the chelation of iron ions by the catechols. Supporting evidence includes the diminished effect of catechols in the presence of EDTA (a potent iron ion chelator) and the observation of a visible band at 450 nm caused by the interaction between caffeic acid and iron ions. Additionally, the visible band (506 nM) was observed in the solution of o-benzenediol and ferric chloride but not in the solution of m- or p-benzenediol and ferric chloride. Thus compounds with adjacent hydroxyl groups on aromatic rings might inhibit hydroxyl radical formation.
A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation
Ursini F.; Maiorino M.; Morazzoni P.; Roveri A.; Pifferi G.
Department of Biological Chemistry, University of Padova, Via Trieste 75, I-35121 Padova Italy
Free Radic. Biol. Med. (USA), 1994, 16/5 (547-553)
In searching for new drug candidates which could help bridge the gaps between free radical oxidations, pathophysiological responses, and pharmacological treatment, a series of flavonoids was screened. The most interesting compound emerging from this screening, the flavone 3'-hydroxyfarrerol (IdB 1031), is presented in this article. This compound is a good inhibitor of microsomal lipid peroxidation induced by either iron-adenosine 5'-diphosphate (ADP) or carbon tetrachloride. The elevated rate constant for the interaction with peroxyl radicals, analysed by the kinetics of inhibition of crocin bleaching in the presence of a diazo initiator, gives an account for the observed antioxidant capacity. When tested on human neutrophils activated by fMLP, IdB 1031 inhibits (ID50:2O microM) respiratory burst. This effect, which is possibly linked to the observed inhibition of protein-kinase C (ID50:5O microM), seems rather specific since IdB 1031 does not inhibit tyr-kinases and casein-kinase-2, while Quercetin and other flavonoids inhibit unspecifically all these enzymes. These effects, as a whole, depict this compound as a drug candidate for diseases in which peroxidative damage is associated with the induction of inflammatory responses and specifically with activation of a respiratory burst of leucocytes.
Prevention of postischemic cardiac injury by the orally active iron chelator 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and the antioxidant (+)-cyanidanol-3
Van der Kraaij A.M.M.; Van Eijk H.G.; Koster J.F.
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, 3000 DR Rotterdam Netherlands
Circulation (USA), 1989, 80/1 (158-164)
In this study, we investigated the role of oxygen-derived free radicals and iron in mediating myocardial injury during ischemia and reperfusion. Iron is of special interest because it may enhance tissue injury during ischemia and reperfusion by catalyzing the formation of highly reactive hydroxyl radicals (by modified Haber-Weiss or Fenton reactions). Rat hearts, perfused by the Langendorff method, were subjected to global ischemia (15 minutes at 37degree C) and reperfusion. The effects of two iron chelators, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) and 5-hydroxy-2-hydroxymethyl-4-pyrone (kojic acid), and one antioxidant, (+)-cyanidanol-3, on contractile function, coronary flow, lactate dehydrogenase release, and lactate production were studied. The combination of these iron chelators is of special importance because L1 is known to prevent lipid peroxidation, induced by ADP/Fe3+ and NADPH in microsomes, in contrast to kojic acid. We found significant protection of contractile function (apex displacement) during reperfusion with 50 microM L1 and 20 microM (+)-cyanidanol-3 (p < 0.01, n = 6), whereas no protection was found with 50 microM kojic acid (n = 6). Measurements of lactate dehydrogenase release during reperfusion showed a protective pattern similar to that found for heart contractile function, although 50 microM kojic acid also showed a significantly lower lactate dehydrogenase release during the first 10 minutes of reperfusion. No differences in coronary resistance or lactate release were found between the various groups. Our findings indicate that iron and oxygen-derived free radicals are important in the pathogenesis of postischemic reperfusion injury probably because of the formation of hydroxyl radicals. During heart ischemia, administration of the orally active iron chelator L1 of the antioxidant (+)-cyanidanol-3 may be a promising approach in establishing postischemic cardiac protection.
Hepatotoxicity of menadione predominates in oxygen-rich zones of the liver lobule
Badr M.Z.; Ganey P.E.; Yoshihara H.; Kauffman F.C.; Thurman R.G.
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599-7365 USA
J. Pharmacol. Exp. Ther. (USA), 1989, 248/3 (1317-1322)
This study was designed to investigate the mechanism of zone-specific hepatotoxicity due to menadione. Infusion of menadione (64-1000 microM) into perfused livers from fasted rats caused a concentration-dependent increase in O2 uptake. During perfusion in the anterograde direction, menadione (1 mM) increased O2 uptake from 115 plus or minus 11 to 142 plus or minus 10 micromol/g/hr within 30 min, followed by a decrease to 92 plus or minus 11 micromol/g/hr over the next 30 min. Trypan blue was taken up by 90% of cells in periportal regions reflecting irreversible cell death, whereas cells in pericentral areas were not damaged. When the hepatic O2 gradient was reversed by perfusing in the retrograde direction, menadione increased O2 uptake initially from 114 plus or minus 11 to 132 plus or minus 14 micromol/g/hr, followed by a decline to 51 plus or minus 12 micromol/g/hr, qualitatively similar to data obtained from perfusions in the natural, anterograde direction. During perfusions in the retrograde direction, however, 95% of cells in pericentral regions were stained with trypan blue whereas those in periportal areas were spared. O2 uptake in specific zones of the liver lobule was then measured with miniature O2 electrodes. When menadione was infused during anterograde perfusions, O2 uptake increased in O2-rich periportal areas from 128 plus or minus 6 to 156 plus or minus 12 micromol/g/hr, but was not altered in pericentral regions. Conversely, during perfusions in the retrograde direction, menadione did not affect O2 uptake in periportal areas, but stimulated uptake in O2-rich pericentral regions from 120 plus or minus 4 to 150 plus or minus 14 micromol/g/hr. Lowering the O2 tension across the lobule by perfusing with buffer saturated with 21% O2 prevented menadione-induced lactate dehydrogenase release and uptake of trypan blue. Thus, menadione increases O2 uptake and damages cells nearly exclusively in O2-rich regions of the liver lobule. Lactate dehydrogenase release and trypan blue uptake due to menadione were prevented by cianidanol (400 microM), a radical scavenger, and allopurinol (1 mM), an inhibitor of xanthine oxidase. Desferrioxamine (100 microM), an iron chelator, prevented trypan blue uptake due to menadione and reduced enzyme release by 38%. Taken together, these results indicate that menadione is an O2-dependent hepatotoxin which acts via the production of radical species.
Iron-load increases the susceptibility of rat hearts to oxygen reperfusion damage. Protection by the antioxidant (+)-cyanidanol-3 and deferoxamine
Van der Kraaij A.M.M.; Mostert L.J.; Van Eijk H.G.; Koster J.F.
Department of Biochemistry I, Erasmus University, 3000 DR Rotterdam Netherlands
Circulation (USA), 1988, 78/2 (442-449)
To investigate whether iron is involved in the reperfusion syndrome by aggravating free radical injury, the hearts from iron-loaded and control rats were perfused under normoxic, anoxic, and reperfusion conditions. Normoxic perfusion revealed no change in coronary flow, contractility, or lactate dehydrogenase (LDH) release between these two groups. Under anoxic and reperfusion conditions, however, we found a significant increase of ventricle fibrillation (56% vs. 0%, p<0.01, n=9), a significantly lower recovery of contractility (21plus or minus7.4% vs 81plus or minus6.6%, mean plus or minus SEM; p<0.001), and a significant increase of LDH release (667plus or minus142 vs. 268plus or minus37 mU LDH/min/g wet wt, mean plus or minus SEM; p<0.05). Administration of either 20 microM of the antioxidant (+)-cyanidanol-3 or 50 microM of the iron-chelator deferoxamine totally prevented the generation of ventricle fibrillation and normalized contractility to control levels in the iron-loaded group. Moreover, 20 microM (+)-cyanidanol-3 significantly lowered LDH release in this period (312plus or minus67 mU), whereas deferoxamine had no protective effect on this LDH release (1,494plus or minus288 mU). Normal hearts appeared to be protected by 20 microM (+)-cyanidanol-3 as well. In this group (n=6), a significantly higher recovery of contractility (97.1plus or minus3.2% vs 81plus or minus6.6%, p<0.05) and a significantly lower release of LDH (110plus or minus27 vs. 268plus or minus37 mU, p<0.05) was found compared with the control group (n=9). No difference in superoxide dismutase or glutathione peroxidase activity was found between the groups. It is concluded that
1) iron-loaded rat hearts are more susceptible to anoxia and oxygen reperfusion damage;
2) iron load itself, under normoxic conditions, does not seem to be harmful; and
3) the antioxidant (+)-cyanidanol-3 is able to protect normal as well as iron-loaded hearts against anoxic and reperfusion damage. We suggest that iron plays an important role in the occurrence of tissue damage and ventricle fibrillation during anoxia and reperfusion, probably through the formation of hydroxyl radicals and/or perferryl oxide.
Hepatocyte injury resulting from the inhibition of mitochondrial respiration at low oxygen concentrations involves reductive stress and oxygen activation
Niknahad H, Khan S, O'Brien PJ
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Chem Biol Interact 1995 Oct 20;98(1):27-44
By correlating lactate/pyruvate ratios and ATP levels, cytotoxicity induced by the mitochondrial respiratory inhibitors or hypoxia:reoxygenation injury can be attributed not only to ATP depletion but also to reductive stress and oxygen activation. Thus hypoxia, cyanide or antimycin markedly increases reductive stress, non-heme Fe release and H2O2 formation in hepatocytes. Cytotoxicity was partly prevented with the ferric chelator desferoxamine, the xanthine oxidase inhibitor oxypurinol and the hydrogen peroxide scavenger glutathione. No lipid peroxidation could be detected and phenolic antioxidants had little effect. However, polyphenolic antioxidants or the superoxide dismutase mimics TEMPO or TEMPOL partly prevented cytotoxicity. Furthermore, increasing the hepatocyte NADH/NAD+ ratio with NADH generating compounds such as ethanol, glycerol, or beta-hydroxybutyrate markedly increased cytotoxicity (prevented by desferoxamine) and further increased the intracellular release of non-heme iron. Cytotoxicity could be prevented by glycolytic substrates (eg. fructose, dihydroxyacetone, glyceraldehyde) or the NADH utilising substrates acetoacetate or acetaldehyde which decreased the reductive stress and prevented intracellular iron release. These results suggest that liver injury resulting from insufficient respiration involves reductive stress which releases intracellular Fe, converts xanthine dehydrogenase to xanthine oxidase and causes mitochondrial oxygen activation. The cell's antioxidant defences are compromised and ATP catabolism contributes to oxygen activation.
Modulating hypoxia-induced hepatocyte injury by affecting intracellular redox state
Khan S, O'Brien PJ
Faculty of Pharmacy, University of Toronto, Ont., Canada.
Biochim Biophys Acta 1995 Nov 9;1269(2):153-61
Hypoxia-induced hepatocyte injury results not only from ATP depletion but also from reductive stress and oxygen activation. Thus the NADH/NAD+ ratio was markedly increased in isolated hepatocytes maintained under 95% N2/5% CO2 in Krebs-Henseleit buffer well before plasma membrane disruption occurred. Glycolytic nutrients fructose, dihydroxyacetone or glyceraldehyde prevented cytotoxicity, restored the NADH/NAD+ ratio, and prevented complete ATP depletion. However, the NADH generating nutrients sorbitol, xylitol, glycerol and beta-hydroxybutyrate enhanced hypoxic cytotoxicity even though ATP depletion was not affected. On the other hand, NADH oxidising metabolic intermediates oxaloacetate or acetoacetate prevented hypoxic cytotoxicity but did not affect ATP depletion. Restoring the cellular NADH/NAD+ ratincreased the intracellular release of iron. Hypoxia-inducedhepatocyte injury was also prevented by oxypurinol, a xanthine oxidase inhibitor. Polyphenolic antioxidants (green tea extracts) or the superoxide dismutase mimic,TEMPO partly prevented cytotoxicity suggesting that reactive oxygen species contributed to the cytotoxicity. The above results suggests that hypoxia induced hepatocyte injury results from sustained reductive stress and oxygen activation.
Protection of rat myocardial phospholipid against peroxidative injury through superoxide-(xanthine oxidase)-dependent, iron-promoted fenton chemistry by the male contraceptive gossypol
Janero D.R.; Burghardt B.
Department of Pharmacology and Chemotherapy, Roche Research Center, Hoffmnan-La Roche, Inc., Nutley, NJ 07110 USA
Biochem. Pharmacol. (United Kingdom), 1988, 37/17 (3335-3342)
Metal-promoted oxygen free-radical chemistry is a cause of tissue damage in many disease states, such as myocardial ischemia. The effect of gossypol, a polyphenolic plant pigment and male contraceptive, on the peroxidation of myocardial membrane phospholipid was studied and quantitatively characterized. As a result of exposure to xanthine oxidase (superoxide)-dependent, iron-promoted Fenton chemistry, cardiac phospholipid was readily peroxidized with defined kinetics. The peroxidation could be blocked by substances which interdict at specific points in the Fenton chemistry: superoxide dismutase, alpha-tocopherol, the iron chelator desferrioxamine, and the xanthine oxidase substrate-analogs allopurinol and oxypurinol. The oxidatve-injury system displayed a characteristic antiperoxidant response to each type of inhibitor. Gossypol, at low micromolar concentrations, profoundly altered the rate and extent of myocardial phospholipid peroxidation. Gossypol was ineffective as a xanthine oxidase inhibitor and as a superoxide scavenger at concentrations that abolished myocardial lipid peroxidation. Since metal chelation was an effective means of preventing lipid peroxidation in this system only when the iron therein was completely chelated, the low anti-peroxidant IC50 for gossypol, 1.1 microM, relative to the concentration of iron (100 microM) did not support a functionally significant antiperoxidant role for gossypol as an iron chelator. Rather, it appears that, at low micromolar gossypol concentrations which approximate the peak plasma concentrations in humans, the antiperoxidant effects of gossypol against superoxide-mediated, iron-promoted lipid damage rest with the ability of gossypol to intercept lipid radical intermediates as a 'chain-breaking' aromatic phenol.
Protective effect of tea polyphenol on rat myocardial injury induced by isoproterenol
Chinese Traditional and Herbal Drugs (China)(Apr) 1995
The ability of tea polyphenol to protect against myocardial injury induced by isoproterenol was studied in rats. Pretreatment with 10 mg/kg intraperitoneal tea polyphenol 5 days before isoproterenol administration decreased malonyldehyde concentration, and creatine phosphokinase and lactic dehydrogenase activities, and inhibited the extent of myocardial injury similar to the action of propranolol. Plasma renin activity was also decreased.
Effect of the interaction of tannins with coexisting substances. Part 2. reduction of heavy metal ions and solubilization of precipitates
Okuda T; Mori K; Shiota M; Ida K
Yakugaku Zasshi 1982 Aug;102(8):735-42
The precipitate formation in the solution of geraniin
(II), tannic acid
(III), or (-)-epigallocatechin gallate
(IV) mixed with that of cadmium, chromium, copper, iron, mercury, manganese, lead or zinc ions at pH 5.4, was investigated. The amount of precipitate decreased with an increase in concentration of I or III but precipitate increased with an elevation of tannin concentration. The precipitates formed were solubilized upon further increase of tannin concentration and when the amount of heavy metal in the supernatant liquor together with the ratio of tannin to heavy metal in the precipitate were increased. Extensive reduction of chromium, ferric, cuprous ions and complex formation occurred in the presence of tannins such as I, II, III and IV. These results indicated that the toxicity of metal ions could be reduced in the presence of tannins and polyphenols.
Free radicals scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. A mechanism for their capillary protective action.
Maffei Facino R, Carini M, Aldini G, Bombardelli E, Morazzoni P, Morelli R
Istituto Chimico Farmaceutico Tossicologico, Milan, Italy.
Arzneimittelforschung 1994 May;44(5):592-601
The scavenging by procyanidines (polyphenol oligomers from Vitis vinifera seeds, CAS 85594-37-2) of reactive oxygen species (ROS) involved in the onset (HO degrees) and the maintenance of microvascular injury (lipid radicals R degrees, RO degrees, ROO degrees) has been studied in phosphatidylcholine liposomes (PCL), using two different models of free radical generation: a) iron-promoted and b) ultrasound-induced lipid peroxidation. In a) lipid peroxidation was assessed by determination of thiobarbituric acid-reactive substances (TBARS); in b) by determination of conjugated dienes, formation of breakdown carbonyl products (as 2,4-dinitrophenylhydrazones) and loss of native phosphatidylcholine. In the iron-promoted (Fenton-driven) model, procyanidines had a remarkable, dose-dependent antilipoperoxidant activity (IC50 = 2.5 mumol/l), more than one order of magnitude greater than that of the monomeric unit catechin (IC50 = 50 mumol/l), activity which is due, at least in part, to their metal-chelating properties. In the more specific model b), which discriminates between the initiator (hydroxyl radical from water sonolysis) and the propagator species of lipid peroxidation (the peroxyl radical, from autooxidation of C-centered radicals), procyanidines are highly effective in preventing conjugated diene formation in both the induction (IC50 = 0.1 mumol/l) and propagation (IC50 = 0.05 mumol/l) phases (the scavenging effect of alpha-tocopherol was weaker, with IC50 of 1.5 and 1.25 mumol/l). In addition, procyanidines at 0.5 mumol/l markedly delayed the onset of the breakdown phase (48 h), totally inhibiting during this time the formation of degradation products (the lag-time induced by alpha-tocopherol was only of 24 h at 10 mumol/l concentration). The HO degrees entrapping capacity of these compounds was further confirmed by UV studies and by electron spin resonance (ESR) spectroscopy, using DMPO as spin trapper: procyanidines markedly reduced, in a dose-dependent fashion, the signal intensity of the DMPO-OH radical spin adduct (100% inhibition at 40 mumol/l). The results of the second part of this study show that procyanidines, in addition to free radical scavenging action, strongly and non-competitively, inhibit xanthine oxidase activity, the enzyme which triggers the oxy radical cascade (IC50 = 2.4 mumol/l). In addition procyanidines non-competitively inhibit the activities of the proteolytic enzymes collagenase (IC50 = 38 mumol/l) and elastase (IC50 = 4.24 mumol/l) and of the glycosidases hyaluronidase and beta-glucuronidase (IC50 = 80 mumol/l and 1.1 mumol/l), involved in the turnover of the main structural components of the extravascular matrix collagen, elastin and hyaluronic acid.
The inhibitory action of chlorogenic acid on the intestinal iron absorption in rats.
Gutnisky A, Rizzo N, Castro ME, Garbossa G
Centro de Estudios Farmacologicos y Botanicos, Buenos Aires, Argentina.
Acta Physiol Pharmacol Ther Latinoam 1992;42(3):139-46
The polyphenols are part of the composition of many foods, it is known the inhibitory effect of tea and coffee through the tannins on iron intestinal absorption; the "yerba mate" (Ilex Paraguarensis) is a beverage widely used in South America, that has a high content of a polyphenol named chlorogenic acid. The present work shows the effect of this substance in nonhem iron absorption. An intestinal loop, was made in rats, to form a closed cavity in a small section of intestine tieing it from the pilorous to a distance of six cm. In this closed cavity a solution of 59Fe was injected with different doses of chlorogenic acid; it was living 20, 40 and 120 minutes into the loop, and after this different times, the blood, spleen, liver, femur and intestine were removed to measure the 59Fe uptake to be compared with the control group. The results gave an intense inhibitory effect on the intestinal iron absorption with doses of 0.58 and 1.7 mM per rat of chlorogenic acid at the different times studied.
Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis by compounds derived from cruciferous vegetables and green tea.
Chung FL, Morse MA, Eklind KI, Xu Y
Division of Chemical Carcinogenesis American Health Foundation, Valhalla, New York 10595.
Ann N Y Acad Sci 1993 May 28;686:186-201; discussion 201-2
We have shown that PEITC and I3C, both of cruciferous origin, inhibited lung tumor formation induced by the tobacco-specific nitrosamine NNK. The inhibition by PEITC is due largely to its inhibitory effect on the enzymes of NNK metabolism, whereas; the inhibition by I3C may be attributed to its ability to induce hepatic enzyme activity of NNK metabolism, which resulted in decreased availability of NNK to the lung. One NNK-induced lung umorigenesis, probably due to its antioxidant property. These studies provide for the first time evidence for the involvement of free radicals in nitrosamine tumorigenesis. The mechanism by which free radicals are generated by NNK treatment is not yet known. The reduced levels of oxidative lesions in lung as a result of EGCG treatment may be related to its ability to reduce reactive oxygen species and/or to chelate iron ion resulting in a decreased production of hydroxyl radicals. Overall, these studies have identified ingredients in cruciferous vegetables and green tea that are inhibitory against lung tumorigenesis induced by NNK in rodents.
Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption.
Siegenberg D, Baynes RD, Bothwell TH, Macfarlane BJ, Lamparelli RD, Car NG, MacPhail P, Schmidt U, Tal A, Mayet F
Department of Medicine, University of Witwatersrand, Johannesburg, South Africa.
Am J Clin Nutr 1991 Feb;53(2):537-41
The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.
Phytic acid. A natural antioxidant.
Graf E, Empson KL, Eaton JW
J Biol Chem 1987 Aug 25;262(24):11647-50
The catalysis by iron of radical formation and subsequent oxidative damage has been well documented. Although many iron-chelating agents potentiate reactive oxygen formation and lipid peroxidation, phytic acid (abundant in edible legumes, cereals, and seeds) forms an iron chelate which greatly accelerates Fe2+-mediated oxygen reduction yet blocks iron-driven hydroxyl radical generation and suppresses lipid peroxidation. Furthermore, high concentrations of phytic acid prevent browning and putrefaction of various fruits and vegetables by inhibiting polyphenol oxidase. These observations indicate an important antioxidant function for phytate in seeds during dormancy and suggest that phytate may be a substitute for presently employed preservatives, many of which pose potential health hazards.
[Effect of polyphenols of coffee pulp on iron absorption]
de Rozo MP, Velez J, Garcia LA
Arch Latinoam Nutr 1985 Jun;35(2):287-96
The effect of the polyphenols of coffee pulp on iron absorption was studied using the method of ligated segments in rats. Optimal conditions to measure iron absorption, were determined using as criteria the concentration of Fe59 and the time that produced the highest value of blood radioactivity. A concentration of 0.4 uCi/dose of Fe59 and a 3-hr period were chosen to measure iron absorption. Experimental groups were formed assigning six rats randomly to each group. Each group was injected with a solution of 59Fe and either with the standard polyphenol solution or with the coffee pulp extract, except the control group which was injected with the Fe59 solution only. The effect of two polyphenol concentrations was also studied. Iron uptake from the duodenum was found to be the best indicator of iron absorption when compared to the sum of iron uptake by the tissues (blood, liver, spleen, kidneys, heart and carcass). Therefore, this indicator was used to interpret the results obtained. Catechin, tannic acid and the coffee pulp extract decreased significantly iron absorption when compared with the control group. The level of polyphenols used in these experiments is similar to the amounts consumed by animals fed coffee pulp at a 10% level. Therefore, we can conclude that the antinutritional effect of coffee pulp polyphenols may be partially due to their capacity to bind iron.
Factors affecting the absorption of iron from cereals.
Gillooly M, Bothwell TH, Charlton RW, Torrance JD, Bezwoda WR, MacPhail AP, Derman DP, Novelli L, Morrall P, Mayet F
Br J Nutr 1984 Jan;51(1):37-46
Non-haem-iron absorption from a variety of cereal and fibre meals was measured in parous Indian women, using the erythrocyte utilization of radioactive Fe method. The present study was undertaken to establish whether alteration of the phytate and polyphenol contents of sorghum (Sorghum vulgare) affected Fe absorption from sorghum meals, and to assess the influence of fibre on Fe absorption. Removing the outer layers of sorghum grain by pearling reduced the polyphenol and phytate contents by 96 and 92% respectively. This treatment significantly increased the geometric mean Fe absorption from 0.017 to 0.035 (t 3.9, P less than 0.005). The geometric mean Fe absorption from a sorghum cultivar that lacked polyphenols (albino sorghum) was 0.043, which was significantly greater than the 0.019 absorbed from bird-proof sorghum, a cultivar with a high polyphenol content (t 2.83, P less than 0.05). Fe was less well absorbed from the phytate-rich pearlings of the albino sorghum than from the pearled albino sorghum (0.015 v. 0.035 (t 8.4, P less than 0.0005]. Addition of sodium phytate to a highly Fe-bioavailable broccoli (Brassica oleracea) meal reduced Fe absorption from 0.185 to 0.037. The geometric mean Fe absorption from malted sorghum porridge was 0.024 when 9.5 mg ascorbic acid were added and 0.094 when the ascorbic acid was increased to 50 mg (t 3.33, P less than 0.005). This enhancing effect of 50 mg ascorbic acid was significantly depressed to 0.04 by tea (t 38.1, P less than 0.0005).
The effect of red and white wines on nonheme-iron absorption in humans.
Cook JD, Reddy MB, Hurrell RF
Department of Medicine, Kansas University Medical Center, Kansas City 66160-7402.
Am J Clin Nutr 1995 Apr;61(4):800-4
The effect of the phenolic compounds in wine was examined in this study by performing radioiron-absorption measurements from extrinsically labeled test meals in 33 human subjects. In four separate studies we observed that absorption was 2- to 3-fold higher from white wine containing a low concentration of polyphenols than from two red wines containing a 10-fold higher concentration of polyphenols. The interaction between the polyphenols and alcohol in wine was evaluated by reducing the alcohol content of the wines by approximately 90%. When the alcohol concentration was reduced, there was a significant 28% decrease in nonheme-iron absorption with red wine but no effect with white wine. The inhibitory effect of red wines with reduced alcohol content was about twofold greater when they were consumed with a small bread roll than when taken without food. Our findings indicate that the inhibitory effect of phenolic compounds in red wine is unlikely to affect iron balance significantly.
Prevention of iron deficiency.
Department of Medicine, University of Goteborg, Sahlgren Hospital, Sweden.
Baillieres Clin Haematol 1994 Dec;7(4):805-14
This chapter discusses different methods to prevent iron deficiency--to reduce iron losses (e.g. reducing menstrual iron losses by using a contraceptive pill or combating of hookworm infestation) or to increase iron absorption. Iron absorption can be increased
(1) by modifying the composition of meals--increasing the content of dietary factors enhancing iron absorption (e.g. meat and ascorbic acid) or reducing the content of factors inhibiting iron absorption such as phytate and iron-binding phenolic compounds,
(2) by increasing the iron content of the diet by fortification with iron, or by
(3) supplementation with iron tablets. Several factors to consider in the choice of strategy are discussed such as the importance of the bioavailability of the diet for the efficacy of iron fortification, the choice of vehicle for iron fortification that is compatible with the iron compound used, the feasibility to increase the bioavailability of the dietary iron by modification of the composition of the diet and the short time available in pregnancy to ensure a sufficient supply of the extra iron needed limiting the effective measures available to supplementation with iron tablets.
Iron absorption and phenolic compounds: importance of different phenolic structures.
Brune M, Rossander L, Hallberg L
Department of Medicine II, University of Goteborg, Sweden.
Eur J Clin Nutr 1989 Aug;43(8):547-57
The phenolic compounds (phenolic monomers, polyphenols, tannins) are considered to interfere with iron absorption by complex formation with iron in the gastro-intestinal lumen, making the iron less available for absorption. Very little is known about the extent to which different types of phenolic compounds of different size and chemical structure inhibit iron absorption. The relationship between iron absorption and the amount and type of phenolic compounds was studied by the extrinsic tag method. The aims of the studies were as follows:
(i) To study the effect of small phenolic compounds with different hydroxylation patterns (gallic acid, catechin, chlorogenic acid) on iron absorption,
(ii) To study the effect of different amounts of a hydrolysable tannin containing ten gallic acid residues (tannic acid) on iron absorption.
(iii) To study the degree of inhibition of iron absorption by some foods and beverages (oregano, spinach, coffee and tea) in relation to their respective content of iron-binding phenolic groups, measured by a newly developed method. The inhibition of iron absorption by tannic acid was strongly dose-related. The smallest amount (5 mg) inhibited absorption by 20 per cent, 25 mg by 67 per cent and 100 mg by 88 per cent. Gallic acid inhibited iron absorption to the same extent as tannic acid, per mol galloyl groups, whereas no inhibition was observed when catechin was added to the test meal. Chlorogenic acid inhibited iron absorption to a lesser extent. Oregano and tea inhibited iron absorption in proportion to their respective content of galloyl groups, whereas the inhibitory effect of spinach was less marked. The inhibiting effect of coffee was explained mainly by its content of galloyl groups, but also by some other factor, probably chlorogenic acid. It is concluded that the content of iron-binding galloyl groups might be a major determinant of the inhibitory effect of phenolic compounds on iron absorption from the diet, whereas the phenolic catechol groups seem to be of minor importance. The results further suggest that the group of condensed tannins do not interfere with iron absorption.