title: Protective effect of naringenin-7-O-glucoside against oxidative stress induced by doxorubicin in H9c2 cardiomyocytes.
abstract: Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but cardiotoxicity limits its clinical use. Although the mechanisms are not entirely understood, reactive oxygen species (ROS) and cardiomyocyte apoptosis appear to be involved in DOX cardiotoxicity. Protection or alleviation of DOX 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, could protect from cardiomyocyte apoptosis and induce endogenous antioxidant enzymes against DOX toxicity, but the effects on intracellular ROS generation and cell membrane stability were not demonstrated. In the present study, we investigated the effects of NARG on H9c2 cell morphology, viability, lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, glutathine peroxidase (GSH-Px) activity, intracellular Ca2+ concentration, and ROS generation. Compared with DOX alone treatment group, the morphological injury of the cells in groups treated by DOX plus NARG was alleviated, cell viability was increased, the amount of released LDH and CK was significantly decreased, the activity of GSH-Px was increased, the content of intracellular Ca2+ and ROS generation was lowered remarkably. These results suggest that NARG could prevent cardiomyocytes from DOX-induced toxicity by their property of stabilizing the cell membrane and reducing ROS generation.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Ji'nan, China. xzyhan@sdu.edu.cn
authors.forename: X Z
authors.initials: XZ
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Gao
authors.forename: Y N
authors.initials: YN
authors.lastname: Cheng
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Sun
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: L L
authors.initials: LL
authors.lastname: Tang
authors.forename: D M
authors.initials: DM
authors.lastname: Ren
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D044950:Flavanones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D044950:Flavanones; D005960:Glucosides; D020011:Protective Agents; D017382:Reactive Oxygen Species; C529068:naringenin-7-O-glucoside; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D003402:Creatine Kinase; D002118:Calcium