Research of antioxidant and anti-inflammatory activity of rutine complex with bivalent iron
Keywords:
LPS, inflammation, cytokines, peroxynitrite, hyperthermia, HUVEC, ROSAbstract
Studies using cell-free systems have shown that chelation of ferrous iron by rutin and formation of the complex (Rt – Fe) resulted in the appearance of site-specific pseudo-peroxidase activity against hydrogen peroxide, but does not affect the ligand’s ability to interact with peroxynitrite. Anti-inflammatory properties of rutin (Rt) and its complex with ferrous iron were studied in vitro under conditions of bacterial lipopolysaccharide (LPS)-induced inflammation in endothelial cells of the human umbilical vein (HUVEC). The Rt – Fe complex at a dose of 50 µmol/L was found to significantly reduce the level of LPS-induced mRNA expression of inflammatory mediators IL-6, IL-1B, IL-8, MCP1 and COX-2 and the level of secretion of IL-6 and IL-8 in the culture medium, while Rt under the same concentration was ineffective. Experiments performed in vivo indicate that prior administration of the Rt – Fe complex in a dose of 12.5 µmol/kg dramatically eliminated LPS-induced pyrogenic reaction of in Wistar rats. From the above data, it can be concluded that complexation with bivalent iron enhances of antioxidant properties of Rt, leads to appearance of anti-inflammatory activity and expands the area of its possible pharmacological use.
References
- Ince C, Mayeux PR, Nguyen T, Gomez H, Kellum JA, Ospina-Tascón GA, et al. The endothelium in sepsis. Shock. 2016;45(3): 259–270. DOI: 10.1097/SHK.0000000000000473.
- Huet O, Dupic L, Harrois A, Duranteau J. Oxidative stress and endothelial dysfunction during sepsis. Frontiers in Bioscience. 2011;16(5):1986 –1995. DOI: 10.2741/3835.
- Afanas’ev IB, Dorozhko AI, Brodskii AV, Kostyuk VA, Potapovitch AI. Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation. Biochemical Pharmacology. 1989;38(11):1763–1769. DOI: 10.1016/00062952(89)90410-3.
- Kostyuk VA, Potapovich AI, Vladykovskaya EN, Korkina LG, Afanas’ev IBA. Influence of metal ions on flavonoid protection against asbestos-induced cell injury. Archives Biochemistry and Biophysics. 2001;385(1):129 –137. DOI: 10.1006/abbi.2000.2118.
- Kostyuk VA, Potapovich AI, Strigunova EN, Kostyuk TV, Afanas’ev IB. Experimental evidence that flavonoid metal complexes may act as mimics of superoxide dismutase. Archives Biochemistry and Biophysics. 2004;428(2):204 –208. DOI: 10.1016/j. abb.2004.06.008.
- Tarahovsky YS, Kim YA, Yagolnik EA, Muzafarov EN. Flavonoid-membrane interactions: Involvement of flavonoid-metal complexes in raft signaling. Biochimica et Biophysica Acta (BBA) – Biomembranes. 2014;1838(5):1235–1246. DOI: 10.1016/j.bbamem. 2014.01.021.
- Kostyuk VA, Potapovich AI, Kostyuk TV, Cherian MG. Metal complexes of dietary flavonoids: evaluation of radical scavenger properties and protective activity against oxidative stress in vivo. Cellular and Molecular Biology. 2007;53(1):61– 68. DOI: 10.1170/T774.
- Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proceedings of the National Academy of Sciences of the United States of America. 1990;87(4):1620 –1624. DOI: 10.1073/pnas.87.4.1620.
- Kooy NW, Royall JA, Ischiropoulos H, Beckman JS. Peroxynitrite-mediated oxidation of dihydrorhodamine 123. Free Radical Biology and Medicine. 1994;16(2):149 –156. DOI: 10.1016/0891-5849(94)90138-4.
- Paxinou E, Chen Q, Weisse M, Giasson BI, Norris EH, Rueter SM, et al. Induction of α-synuclein aggregation by intracellular nitrative insult. The Journal of Neuroscience. 2001;21(20):8053–8061. DOI: 10.1523/JNEUROSCI.21-20-08053.2001.
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402– 408. DOI: 10.1006/meth.2001.1262.
- Rudaya AY, Steiner AA, Robbins JR, Dragic AS, Romanovsky AA. Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2005;289(5):R1244 –1252. DOI: 10.1152/ajpregu.00370.2005.
- Sorata Y, Takahama U, Kimura M. Protective effect of quercetin and rutin on photosensitized lysis of human erythrocytes in the presence of hematoporphyrin. Biochimica et Biophysica Acta (BBA) – Biomembranes. 1984;799(3):313–317.
- Rebrin I, Bregere C, Gallaher TK, Sohal RS. Detection and characterization of peroxynitrite-induced modifications of tyrosine, tryptophan, and methionine residues by tandem mass spectrometry. Methods in Enzymology. 2008;441:283–294. DOI: 10.1016/S00766879(08)01215-9.
- Schindler R, Mancilla J, Endres S, Ghorbani R, Clark SC, Dinarello CA. Correlations and interactions in the production of interleukin-6 (IL-6), IL-I and tumour necrosis factor (TNF) in human blood mononuclear cells: IL-6 supresses IL-l and TNF. Blood. 1990;75(1):40 – 47.
- Gao J, Zhao WX, Zhou LJ, Zeng BX, Yao SL, Liu D, et al. Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction. Inflammation Research. 2006;55(9):385–392. DOI: 10.1007/s00011-006-5116-0.
- Lu JL, Schmiege LM, Kuo L, Liao JC. Downregulation of endothelial constitutive nitric oxide synthase expression by lipopolysaccharide. Biochemical and Biophysical Research Communications. 1996;225(1):1–5. DOI: 10.1006/bbrc.1996.1121.
Downloads
Additional Files
Published
Issue
Section
License
The authors who are published in this journal agree to the following:
- The authors retain copyright on the work and provide the journal with the right of first publication of the work on condition of license Creative Commons Attribution-NonCommercial. 4.0 International (CC BY-NC 4.0).
- The authors retain the right to enter into certain contractual agreements relating to the non-exclusive distribution of the published version of the work (e.g. post it on the institutional repository, publication in the book), with the reference to its original publication in this journal.
- The authors have the right to post their work on the Internet (e.g. on the institutional store or personal website) prior to and during the review process, conducted by the journal, as this may lead to a productive discussion and a large number of references to this work. (See The Effect of Open Access.)










