Naringenin-7-O-glucoside protects against doxorubicin-induced toxicity in H9c2 cardiomyocytes by induction of endogenous antioxidant enzymes.
Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity that limits its clinical use by generation of reactive oxygen species (ROS) and apoptosis. Protection or alleviation of doxorubicin cardiotoxicity can be achieved by administration of natural phenolic compounds via activating endogenous defense systems and antiapoptosis. Naringenin-7-O-glucoside (NARG), isolated from Dracocephalum rupestre Hance, has been demonstrated to protect against cardiomyocyte apoptosis. In the present study, we investigated the effects of NARG on endogenous antioxidant enzymes against doxorubicin toxicity and the potential role of extracellular signal-regulated kinase (ERK) in regulation of NARG-induced Nrf2-dependent gene expression in H9c2 cardiomyocytes. The mRNA expression of glutamate-cysteine ligase modifier subunit (GCLM) and glutamate-cysteine ligase catalytic subunit (GCLC) was upregulated by NARG as detected by RT-PCR. NARG (10, 20, and 40microM) pretreatment increased NAD (P) H: quinone oxidoreductase (NQO1), ERK, and Nrf2 protein levels in cardiomyocytes as detected by Western blotting. These results suggest that NARG could prevent cardiomyocytes from doxorubicin-induced toxicity by induction of endogenous antioxidant enzymes via phosphorylation of ERK1/2 and nuclear translocation of Nrf2.
Han
Xiuzhen
X
Department of Natural Product Chemistry, Shandong University, Jinan 250012, China.
Pan
Jihong
J
Ren
Dongmei
D
Cheng
Yanna
Y
Fan
Peihong
P
Lou
Hongxiang
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D044950:Flavanones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation; D021381:Protein Transport; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D044950:Flavanones; D005960:Glucosides; D013778:Tetrazolium Salts; D013844:Thiazoles; C529068:naringenin-7-O-glucoside; D008315:Malondialdehyde; D004317:Doxorubicin; D011794:Quercetin; D048049:Extracellular Signal-Regulated MAP Kinases; C022616:thiazolyl blue; D005978:Glutathione