Effects of Long-Term Use of Flavonoids on the Absorption and Tissue Distribution of Orally Administered Doses of Trace Elements in Rats

DOI: 10.4236/pp.2012.34065   PDF   HTML     5,944 Downloads   9,180 Views   Citations


The risk of pharmacokinetic polyphenols-trace elements interaction may undesirable therapeutic outcomes. We evaluate the long-term use of silibinin, epigallocatechin (ECGC), quercetin and rutin on the absorption and tissue distribution of zinc, copper and iron after single oral doses in rats. Five groups of rats were either with olive oil as control or with one of the polyphenols silibinin, EPGC, quercetin or rutin, administered orally as oily solutions for 30 days. At day 30, a solution contains sulphate salt of zinc, copper and iron was administered orally; 3 hrs later blood samples, tissues of brain, kidney and liver were obtained for evaluation of the elements levels. The results showed that the polyphenols increased both serum and tissue levels of these elements compared with controls. This effect was relatively varied according to the structural differences among flavonoids. In conclusion, long-term use of supraphysiological doses of flavonoids increase absorption of Zn, Cu and Fe and their tissue availability in brain, kidney and liver; this effect seems to be different with variations in structural features.

Share and Cite:

A. Jaccob, S. Hussain and S. Hussain, "Effects of Long-Term Use of Flavonoids on the Absorption and Tissue Distribution of Orally Administered Doses of Trace Elements in Rats," Pharmacology & Pharmacy, Vol. 3 No. 4, 2012, pp. 474-480. doi: 10.4236/pp.2012.34065.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] S. Pascual-Teresa, D. A. Moreno and C. Garcia-Viguera, " Flavanols and anthocyanins in cardiovascular health: a review of current evidence," International Journal Molecular Sciences, Vol. 11, 2010, pp. 1679-1703.
[2] E. Middleton, C. Kandaswami and T. C. Theoharides, " The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease and cancer, " Pharmacological Reviews, Vol 52, 2000, pp. 673-751.
[3] V. M. Adhami and H. Mukhtar, " Polyphenols from green tea and pomegranate for prevention of prostate cancer, " Free Radicals Research, Vol. 40, No. 10, 2006, pp. 1095-1104.
[4] H. E. Seifried, D. E. Anderson, E. I. Fisher and J. A. Milner, " A review of the interaction among dietary antioxidants and reactive oxygen species, " Journal of Nutrition and Biochemistry, Vol. 18, No. 9, 2007, pp. 567-579.
[5] B. Halliwell, " Dietary polyphenols: good, bad, or indifferent for your health?," Cardiovascular Research, Vol. 73, No. 2, 2007, pp. 341-347.
[6] S. C. Thomasset, D. P. Berry, G. Garcea, T. Marczylo, W. P. Steward and A. J. Gescher, " Dietary polyphenolic phytochemicals-promising cancer chemopreventive agents in humans? A review of their clinical properties," International Journal of Cancer, Vol. 120, No. 3, 2007, pp. 451-458.
[7] J. C. Espin, M. T. Garcia-Conesa and F. A. Tomas-Barberan," Nutraceuticals: facts and fiction," Phytochemistry, Vol. 68, 2007, pp. 2986-3008.
[8] R. Cermak," Effect of dietary flavonoids on pathways involved in drug metabolism," Expert Opinion in Drug Metabolism and Toxicology, Vol. 4, 2008, pp. 17-35.
[9] J. Kennedy, C. C. Wang and C. H. Wu," Patient disclosure about herb and supplement use among adults in the US," Evidence Based Complement Alternative Medicine, Vol. 5, 2008, pp. 451-456.
[10] O. O. Babalola, R. E. Okonji, J. O. Atoyebi, T. F. Sennuga, et al," Distribution of lead in selected organs and tissues of albino rats exposed to acute lead toxicity," Scientific Research Essay, Vol. 5, No. 9, 2010, pp. 845-848.
[11] R. A. Jacob, H. H. Sandstead, J. M. Munoz, L. M. Klevay and D. B. Milne," Whole body surface loss of trace metals in normal males," American Journal of Clinical Nutrition, Vol. 34, 1981, pp. 1379-1383.
[12] Z. Gao, H. Xu and K. Huang," Effects of rutin supplementation on antioxidant status and Iron, Copper and Zinc contents in mouse liver and brain," Biological Trace Elements Research, Vol. 88, No. 3, 2002, pp. 271-279.
[13] O. Akinloye, F. M. Abbiyesuku, O. O. Oguntibeju, A. O. Arowojolu and E. J. Truter," The impact of blood and seminal plasma zinc and copper concentrations on spermogram and hormonal changes in infertile Nigerian men," Reproductive Biology, Vol. 11, No. 2, 2011, pp. 83-98.
[14] C. F. Skibola and M. T. Smith," Potential health impacts of excessive flavonoid intake," Free Radicals in Biology and Medicine, Vol. 29, 2000, pp. 375-383.
[15] I. Morel, G. Lescoat, P. Cognel, O. Sergent, N. Pasdelop, P. Brissot, et al," Antioxidants and iron-iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures," Biochemical Pharmacology, Vol. 45, 1993, pp. 13-19.
[16] P. Sestili, A. Guidarelli, M. Dacha and O. Cantoni," Quercetin prevents DNA single strand breakage and cytotoxicity caused by tert-butylhydroperoxide: free radical scavenging versus iron chelating mechanism," Free Radicals in Biology and Medicine, Vol. 25, 1998, pp. 196-200.
[17] S. Samman, B. Sandstrom, M. B. Toft, K. Bukhave, M. Jensen, S. S. Sorensen and M. Hansen," Green tea or rosemary extract added to foods reduces nonheme-iron absorption," American Journal of Clinical Nutrition, Vol. 73, 2001, pp. 607-612.
[18] M. Murariu, E. S. Dragan and G. Drochioiu," Electrospray ionization mass spectrometric approach of conformationally-induced metal binding to oligopeptides," European Journal of Mass Spectrometry, Vol. 16, 2010, pp. 511.
[19] G. Drochioiu, M. Manea, M. Dragusanu, M. Murariu, et al," Interaction of beta-amyloid(1-40) peptide with pairs of metal ions: An electrospray ion trap mass spectrometric model study," Biophysical Chemistry Vol. 144, No. 1-2, 2009, pp. 9-20.
[20] Y. M. Bao, M. Choct, P. A. Iji and K. Bruerton," Effect of organically complexed Copper, Iron, Manganese and Zinc on broiler performance, mineralexcretion and accumulation in tissues," Journal of Applied Poultry Research, Vol. 16, 2007, pp. 448-455.
[21] L. Nollet, J. D. van der Klis, M. Lensing and P. Spring," The effect of replacing inorganic with organic trace minerals in broiler diets on productive performance and mineral excretion," Journal of Applied Poultry Research, Vol. 16, 2007, pp. 592-597.
[22] A. G. Abdallah, O. M. El-Husseiny and K. O. Abdel-Latif," Influence of some dietary organic mineral supplementations on broiler performance," International Journal of Poultry Sciences, Vol. 8, 2009, pp. 291-298.
[23] M. Andjelkovic, J. van Camp, B. de Meulenaer, G. Depaemelaere, et al," Iron-chelation properties of phenolic acids bearing catechol and galloyl groups," Food Chemistry, Vol. 98, 2006, pp. 23-31.
[24] K. Sreenivasulu, P. Raghu and K. M. Nair," Polyphenol-rich beverages enhance zinc uptake and metallo-thionein expression in Caco-2 cells," Journal of Food Sciences, Vol. 75, No. 4, 2010, pp. H123-H128.
[25] C. Coudray, C. Bousset, D. Pepin, J. C. Tressol, et al," Short-term ingestion of chlorogenic or caffeic acids decreases zinc but not copper absorption in rats, utilization of stable isotopes and inductively coupled plasma mass spectrometry technique," British Journal of Nutrition, Vol. 80, 1998, pp. 575-584.
[26] C. Coudray, J. C. Tressol, C. Feillet-Coudray, J. Bellanger, et al," Long-term consumption of red wine does not modify intestinal absorption or status of zinc and copper in rats," Journal of Nutrition, Vol. 130, 2000, pp. 1309-1313.
[27] D. G. Salinas, M. de La Fuente and J. G. Reyes," Changes of enzyme activity in lipid signaling pathways related to substrate reordering," Biophysics Journal, Vol. 89, No. 2, 2005, pp. 885-894.
[28] N. T. de Gomez Dumm, A. M. Giammona, L. A. Touceda and C. Raimondi," Lipid abnormalities in chronic renal failure patients undergoing hemodialysis," Medicina (B Aires), Vol. 61, No. 2, 2001, pp. 142-146.
[29] R. E. Navarro, H. Santacruz and M. Inoue," Complexation of epigallocatechin gallate (a green tea extract, EGCG) with Mn2+: nuclear spin relaxation by the paramagnetic ion," Journal of Inorganic Biochemistry, Vol. 99, No. 2, 2005, pp. 584-588.
[30] T. Hashimoto, S. Kumazawa, F. Nanjo, Y. Hara and T. Nakayama," Interaction of tea catechins with lipid bilayers investigated with liposome systems," Bioscience Bio-technology and Biochemistry, Vol. 63, No. 12, 1999, pp. 2252-2255.
[31] K. Kajiya, S. Kumazawa and T. Nakayama," Steric effects on interaction of tea catechins with lipid bilayers," Bioscience Biotechnology and Biochemistry, Vol. 65, No. 12, 2001, pp. 2638-2643.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.