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Mar Drugs
2014 May 13;125:2922-36. doi: 10.3390/md12052922.
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Echinochrome A protects mitochondrial function in cardiomyocytes against cardiotoxic drugs.
Jeong SH
,
Kim HK
,
Song IS
,
Lee SJ
,
Ko KS
,
Rhee BD
,
Kim N
,
Mishchenko NP
,
Fedoryev SA
,
Stonik VA
,
Han J
.
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Echinochrome A (Ech A) is a naphthoquinoid pigment from sea urchins that possesses antioxidant, antimicrobial, anti-inflammatory and chelating abilities. Although Ech A is the active substance in the ophthalmic and cardiac drug Histochrome®, its underlying cardioprotective mechanisms are not well understood. In this study, we investigated the protective role of Ech A against toxic agents that induce death of rat cardiac myoblast H9c2 cells and isolated rat cardiomyocytes. We found that the cardiotoxic agents tert-Butyl hydroperoxide (tBHP, organic reactive oxygen species (ROS) inducer), sodium nitroprusside (SNP; anti-hypertension drug), and doxorubicin (anti-cancer drug) caused mitochondrial dysfunction such as increased ROS level and decreased mitochondrial membrane potential. Co-treatment with Ech A, however, prevented this decrease in membrane potential and increase in ROS level. Co-treatment of Ech A also reduced the effects of these cardiotoxic agents on mitochondrial oxidative phosphorylation and adenosine triphosphate level. These findings indicate the therapeutic potential of Ech A for reducing cardiotoxic agent-induced damage.
Figure 1. Chemical structure of echinochrome A (Ech A).
Figure 4. Ech A attenuated cardiotoxic agent-induced mitochondrial damage in isolated rat cardiomyocytes. Isolated rat cardiomyocytes were treated with cardiotoxic agents for 1 h, after which ROS level (CM-H2DCFDA, green color) and mitochondrial membrane potential (ΔΨm, TMRE, red color) were measured using confocal microscopy. (A) Cardiotoxic agent, tert-Butyl hydroperoxide (tBHP) rapidly increased ROS level (green, ROS indicator) and decreased mitochondrial membrane potential (red, ΔΨm). Co-treatment with Ech A attenuated the increase in ROS level and preserved mitochondrial membrane potential. Data are summarized in (B). (C) Sodium nitroprusside (SNP) rapidly increased ROS level (green, ROS indicator) and decreased mitochondrial membrane potential (red, ΔΨm). Co-treatment with Ech A attenuated the increase in ROS level and preserved mitochondrial membrane potential. Data are summarized in (D). (E) Dox rapidly increased ROS level (green, ROS indicator) and decreased mitochondrial membrane potential (red, ΔΨm). Co-treatment with Ech A attenuated the increase in ROS level and preserved mitochondrial membrane potential. Data are summarized in (F). Four independent in vitro experiments were performed. P < 0.05 vs. cardiotoxic agent single treatment group. Scale bar = 20 μm.
Figure 7. Ech A regulates ERK1/2, JNK, and p38 signaling pathways. H9c2 cells were treated with cardiotoxic agents for 1 h, after which western blotting was performed. And we analyzed the western blot bands though quantification with multi-gage. Cardiotoxic agents induced phosphorylation of ERK1/2, JNK, and p38, but co-treatment with Ech A inhibited this phosphorylation. Three independent in vitro experiments were performed. P < 0.05 vs. cardiotoxic agent single treatment group.
Amoroso,
Sodium nitroprusside prevents chemical hypoxia-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells.
2000, Pubmed
Amoroso,
Sodium nitroprusside prevents chemical hypoxia-induced cell death through iron ions stimulating the activity of the Na+-Ca2+ exchanger in C6 glioma cells.
2000,
Pubmed
Anderson,
Distribution of spinochrome pigments in echinoids.
1969,
Pubmed
,
Echinobase
Bernabé,
Sodium nitroprusside-induced mitochondrial apoptotic events in insulin-secreting RINm5F cells are associated with MAP kinases activation.
2001,
Pubmed
Binaschi,
Anthracyclines: selected new developments.
2001,
Pubmed
Buĭmov,
[Effect of the bioantioxidant histochrome on myocardial injury in reperfusion therapy on patients with myocardial infarction].
2002,
Pubmed
Carvalho,
Doxorubicin: the good, the bad and the ugly effect.
2009,
Pubmed
Chae,
Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner.
2001,
Pubmed
Chen,
Activation of AMP-activated protein kinase contributes to doxorubicin-induced cell death and apoptosis in cultured myocardial H9c2 cells.
2011,
Pubmed
Chu,
Modulation of telomerase and signal transduction proteins by hexyl-ALA-photodynamic therapy (PDT) in human doxorubicin resistant cancer cell models.
2012,
Pubmed
Clark,
Nitroglycerin and sodium nitroprusside: potential contributors to postoperative bleeding?
2012,
Pubmed
Egorov,
[Histochrome, a new antioxidant, in the treatment of ocular diseases].
1999,
Pubmed
Ferrans,
Pathogenesis and prevention of doxorubicin cardiomyopathy.
1997,
Pubmed
Holley,
Carbon monoxide poisoning in racing car drivers.
1999,
Pubmed
Jeong,
HS-1793, a recently developed resveratrol analogue protects rat heart against hypoxia/reoxygenation injury via attenuating mitochondrial damage.
2013,
Pubmed
Jeong,
An analogue of resveratrol HS-1793 exhibits anticancer activity against MCF-7 cells via inhibition of mitochondrial biogenesis gene expression.
2012,
Pubmed
Jones,
Anthracycline cardiotoxicity.
2006,
Pubmed
Kang,
The antioxidant phenylaminoethyl selenide reduces doxorubicin-induced cardiotoxicity in a xenograft model of human prostate cancer.
2011,
Pubmed
Kim,
NecroX as a novel class of mitochondrial reactive oxygen species and ONOO⁻ scavenger.
2010,
Pubmed
Kitamura,
Manipulation of cardiac phosphatidylinositol 3-kinase (PI3K)/Akt signaling by apoptosis regulator through modulating IAP expression (ARIA) regulates cardiomyocyte death during doxorubicin-induced cardiomyopathy.
2014,
Pubmed
Lee,
NecroX-5 suppresses sodium nitroprusside-induced cardiac cell death through inhibition of JNK and caspase-3 activation.
2014,
Pubmed
Lee,
Protective effect of survivin in Doxorubicin-induced cell death in h9c2 cardiac myocytes.
2013,
Pubmed
Li,
Opposing roles of p47phox in basal versus angiotensin II-stimulated alterations in vascular O2- production, vascular tone, and mitogen-activated protein kinase activation.
2004,
Pubmed
Meloche,
The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition.
2007,
Pubmed
Minotti,
Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity.
2004,
Pubmed
Mischenko,
Echinamines A and B, first aminated hydroxynaphthazarins from the sea urchin Scaphechinus mirabilis.
2005,
Pubmed
,
Echinobase
Rabkin,
Nitroprusside induces cardiomyocyte death: interaction with hydrogen peroxide.
2000,
Pubmed
Rasbach,
Signaling of mitochondrial biogenesis following oxidant injury.
2007,
Pubmed
Roux,
ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions.
2004,
Pubmed
Shvilkin,
[Effect of echinochrom on experimental myocardial reperfusion injury].
1991,
Pubmed
Sun,
Myocardial repair/remodelling following infarction: roles of local factors.
2009,
Pubmed
Thomson,
Distribution of naturally occurring quinones.
1991,
Pubmed
Velez,
p53 Regulates oxidative stress-mediated retrograde signaling: a novel mechanism for chemotherapy-induced cardiac injury.
2011,
Pubmed
Wang,
Antioxidant activities of oleanolic acid in vitro: possible role of Nrf2 and MAP kinases.
2010,
Pubmed
Westhoff,
A physiogenomic approach to study the regulation of blood pressure.
2005,
Pubmed
Yang,
Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress.
2011,
Pubmed