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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.
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