Dehydrosilybin attenuates the production of ROS in rat cardiomyocyte mitochondria with an uncoupler-like mechanism
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Analysis of Variance MeSH
- Benzimidazoles MeSH
- Fluorescent Dyes MeSH
- Inhibitory Concentration 50 MeSH
- Carbocyanines MeSH
- Myocytes, Cardiac metabolism MeSH
- Rats MeSH
- Mitochondria metabolism MeSH
- Molecular Structure MeSH
- Rats, Wistar MeSH
- Reactive Oxygen Species metabolism MeSH
- Rotenone toxicity MeSH
- Silymarin chemistry pharmacology MeSH
- Oxygen Consumption drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine MeSH Browser
- Benzimidazoles MeSH
- dehydrosilybin MeSH Browser
- Fluorescent Dyes MeSH
- Carbocyanines MeSH
- Reactive Oxygen Species MeSH
- Rotenone MeSH
- Silymarin MeSH
Reactive oxygen species (ROS) originating from mitochondria are perceived as a factor contributing to cell aging and means have been sought to attenuate ROS formation with the aim of extending the cell lifespan. Silybin and dehydrosilybin, two polyphenolic compounds, display a plethora of biological effects generally ascribed to their known antioxidant capacity. When investigating the cytoprotective effects of these two compounds in the primary cell cultures of neonatal rat cardiomyocytes, we noted the ability of dehydrosilybin to de-energize the cells by monitoring JC-1 fluorescence. Experiments evaluating oxygen consumption and membrane potential revealed that dehydrosilybin uncouples the respiration of isolated rat heart mitochondria albeit with a much lower potency than synthetic uncouplers. Furthermore, dehydrosilybin revealed a very high potency in suppressing ROS formation in isolated rat heart mitochondria with IC(50) = 0.15 μM. It is far more effective than its effect in a purely chemical system generating superoxide or in cells capable of oxidative burst, where the IC(50) for dehydrosilybin exceeds 50 μM. Dehydrosilybin also attenuated ROS formation caused by rotenone in the primary cultures of neonatal rat cardiomyocytes. We infer that the apparent uncoupler-like activity of dehydrosilybin is the basis of its ROS modulation effect in neonatal rat cardiomyocytes and leads us to propose a hypothesis on natural ischemia preconditioning by dietary polyphenols.
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Biochem Biophys Res Commun. 1981 May 15;100(1):37-44 PubMed
J Bioenerg Biomembr. 1999 Oct;31(5):431-45 PubMed
J Phys Chem A. 2008 Feb 7;112(5):1054-63 PubMed
Cardiovasc Res. 2006 Nov 1;72(2):313-21 PubMed
Bioorg Med Chem. 2004 Nov 1;12(21):5677-87 PubMed
J Biol Chem. 1996 Feb 2;271(5):2615-20 PubMed
Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R491-511 PubMed
Phytother Res. 2008 Sep;22(9):1213-8 PubMed
J Bioenerg Biomembr. 2009 Apr;41(2):133-6 PubMed
J Biol Chem. 2002 Dec 20;277(51):49965-75 PubMed
J Bioenerg Biomembr. 2009 Feb;41(1):41-7 PubMed
Hepatology. 2010 Jun;51(6):1912-21 PubMed
Free Radic Biol Med. 2009 Aug 15;47(4):333-43 PubMed
J Pharmacol Exp Ther. 2006 Jan;316(1):200-7 PubMed
Methods Enzymol. 1990;186:209-20 PubMed
Annu Rev Biochem. 2006;75:69-92 PubMed
Biophys J. 1999 Jan;76(1 Pt 1):469-77 PubMed
FEBS Lett. 1997 Jul 7;411(1):77-82 PubMed
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2001 Dec;145(2):49-55 PubMed
Anal Biochem. 1997 Nov 15;253(2):162-8 PubMed
Anal Biochem. 1976 May 7;72:248-54 PubMed
Int J Biochem Cell Biol. 2005 Dec;37(12):2478-503 PubMed
Int J Biochem Cell Biol. 2007;39(1):44-84 PubMed
J Biol Chem. 1999 Sep 10;274(37):26003-7 PubMed
Cardiovasc Res. 2006 Nov 1;72(2):322-30 PubMed
Chem Biol Interact. 2005 Apr 15;152(2-3):67-78 PubMed
Int J Biochem Cell Biol. 2008;40(10):2098-109 PubMed
Free Radic Biol Med. 2000 May 15;28(10):1456-62 PubMed
J Mol Cell Cardiol. 2009 Jun;46(6):858-66 PubMed
Curr Med Chem. 2007;14(3):315-38 PubMed
Am J Physiol Cell Physiol. 2007 Jan;292(1):C137-47 PubMed
Biosci Rep. 2006 Jun;26(3):231-43 PubMed
Free Radic Biol Med. 2009 Mar 15;46(6):745-58 PubMed
Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5995-9 PubMed
Biochim Biophys Acta. 1998 Feb 25;1363(2):100-24 PubMed
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