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The Aqueous Extract of TA Bark Reduces Mitochondrial Oxidative Stress Induced by Doxorubicin in H9c2 cells
Author(s) -
Liu Shi,
Bishop Sarah
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.777.6
Subject(s) - oxidative stress , doxorubicin , chemistry , cardiotoxicity , reactive oxygen species , mitochondrion , pharmacology , apoptosis , oxidative phosphorylation , biochemistry , microbiology and biotechnology , toxicity , biology , chemotherapy , medicine , organic chemistry
Increased oxidative stress (OS) is one of mechanisms responsible for cardiotoxicity induced by doxorubicin (DOX), a commonly‐used anticancer chemotherapeutic agent. We have found that the aqueous extract of TA bark ( TA AqE ) has a carditonic effect on adult ventricular myocytes. This study is to investigate effects of TA AqE on DOX‐induced OS in H9c2 cells, a cell‐line model derived from embryonic rat heart. Fluorescence microscopy (FM) with OS‐sensitive probes and immunocytochemistry (ICC) were used to determine the level of oxidative status and target proteins. H9c2 cells were treated in the absence or presence of TA AqE without or with exposure to 1 μM DOX for 2 to 24 hours. FM of dihydroethidium showed that TA AqE decreased DOX‐induced increase in O 2 ‐• production in a concentration‐dependent manner (1‐100 μg/ml) after 2 hr treatment. Similar inhibitory effects of TA AqE were observed after 24 hr treatment of DOX. In contrast, FM of dichlorodihydro‐fluorescein showed that TA AqE had no significant effect on DOX‐induced increase in the H 2 O 2 ‐associated OS, suggestive of various reactive oxygen species involved in increased OS induced by DOX. Moreover, FM of Mitotracker‐Orange showed that TA AqE also attenuated DOX‐induced increase in mitochondrial OS in a concentration‐dependent manner, while TA AqE (100 μg/ml) per se induced 20% reduction of mitochondrial OS in cells not treated with DOX. In addition, ICC detection of Cytochrome C (CytC) showed that TA AqE attenuated DOX‐induced increase in mitochondrial release of CytC after 24‐h treatment. In conclusion, TA AqE appears to protect primarily mitochondria from increased O 2 ‐• production caused by DOX.