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Preventive Effects of Ellagic Acid Against Doxorubicin-Induced Cardio-Toxicity in Mice

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Abstract

Preventive effects of ellagic acid against doxorubicin-induced cardiac oxidative, inflammatory and apoptotic stress were examined. This agent at 0.25, 0.5 or 1 % was added in feed and supplied to mice for 8 weeks, and followed by doxorubicin treatment. Ellagic acid intake increased its deposit in heart. Pre-intake of this compound at 0.5 and 1 % significantly attenuated doxorubicin caused increase in plasma creatine phosphokinase activity. Doxorubicin treatment decreased glutathione content, increased reactive oxygen species (ROS), malonyldialdehyde (MDA), interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1 and tumor necrosis factor-alpha levels, declined glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities, and enhanced xanthine oxidases (XO) activity in heart. Ellagic acid intake dose-dependently reserved glutathione content, lowered ROS and MDA levels, and reduced XO activity. This compound at 0.5 and 1 % retained GPX and SOD activities, and decreased cytokines in heart. Doxorubicin treatment raised cardiac activity and protein production of caspase-3, nuclear factor kappa B (NF-κB) p50 and p65. Ellagic acid dose-dependently lowered caspase-3 activity and cleaved caspase-3 formation, and at 0.5 and 1 % declined activity and protein level of NF-κB. Doxorubicin treatment also up-regulated cardiac expression of p-p38, p-ERK 1/2 and p-JNK, and ellagic acid at 0.5 and 1 % suppressed p-p38 expression and at 1 % down-regulated p-ERK 1/2 expression. These findings suggest that ellagic acid is a potent cardiac protective agent against doxorubicin.

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Abbreviations

AT:

Antithrombin

CPK:

Creatine phosphokinase

CRP:

c-Reactive protein

GPX:

Glutathione peroxidase

GSH:

Glutathione

IL:

Interleukin

LDH:

Lactate dehydrogenase

MAPK:

Mitogen-activated protein kinase

MCP:

Monocyte chemoattractant protein

MDA:

Malonyldialdehyde

NF-κB:

Nuclear factor kappa B

PAI:

Plasminogen activator inhibitor

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TNF:

Tumor necrosis factor

XO:

Xanthine oxidases

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Authors and Affiliations

  1. School of Medicine, Chung Shan Medical University, Taichung City, Taiwan

    Ming-cheng Lin

  2. Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City, Taiwan

    Ming-cheng Lin

  3. Department of Health and Nutrition Biotechnology, Asia University, Taichung City, Taiwan

    Mei-chin Yin

  4. Department of Nutrition, China Medical University, 16th Floor, 91, Hsueh-shih Rd., Taichung City, Taiwan

    Mei-chin Yin

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  1. Ming-cheng Lin
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Correspondence to Mei-chin Yin.

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Lin, Mc., Yin, Mc. Preventive Effects of Ellagic Acid Against Doxorubicin-Induced Cardio-Toxicity in Mice. Cardiovasc Toxicol 13, 185–193 (2013). https://doi.org/10.1007/s12012-013-9197-z

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  • DOI: https://doi.org/10.1007/s12012-013-9197-z

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