Effect and mechanism of Sorbus pohuashanensis (Hante) Hedl. flavonoids protect against arsenic trioxide-induced cardiotoxicity

Autor: Wenli Liu, Rui Hai Liu, Xiaojin Yu, Keli Yun, Zhenyu Wang, Zunpeng Shu, Zhengqing Li, Yuan Ning, Haina Bai
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Spectrometry
Mass
Electrospray Ionization
Antioxidant
Cardiotonic Agents
Cell Survival
medicine.medical_treatment
Pharmacology
medicine.disease_cause
Antioxidants
Arsenicals
Superoxide dismutase
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Arsenic Trioxide
medicine
Animals
Sorbus
Arsenic trioxide
chemistry.chemical_classification
Flavonoids
Reactive oxygen species
Mice
Inbred BALB C
biology
Cell Death
L-Lactate Dehydrogenase
Glutathione peroxidase
Myocardium
Oxides
General Medicine
Cardiotoxicity
Oxidative Stress
030104 developmental biology
chemistry
Biochemistry
Proto-Oncogene Proteins c-bcl-2
Catalase
030220 oncology & carcinogenesis
Caspases
biology.protein
Creatine kinase
Reactive Oxygen Species
Oxidative stress
Signal Transduction
Zdroj: Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 88
ISSN: 1950-6007
Popis: The cardiotoxicity of arsenic trioxide (ATO) limits its clinical application in cancer treatment. Evidences suggest that sorbus has antioxidant activity and its consumption has been linked with improved cardioprotection. In this study, we investigated the cardio-protective effect and mechanisms of Sorbus pohuashanensis (Hante) Hedl. flavonoids (SPF) against ATO in BALB/c mice and H9c2 cells. Eleven major flavonoids were confirmed by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS). SPF recovered the ATO-induced disordered electrocardiogram (ECG) and abnormal cardiac structure in the heart of mice. At the same time, SPF significantly reduced levels of creatine kinase (CK), creatine kinase-MB (CK-MB) lactate dehydrogenase (LDH), and glutamic oxaloacetic transaminase (GOT) against ATO-induced injury and inhibited ATO-induced apoptosis both in vivo and in vitro. In addition, SPF regulated ATO-induced oxidative stress damage by increasing the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro, and reducing reactive oxygen species (ROS). Analysis of the oxidative stress pathways showed that SPF prevented the ATO-induced downregulation of phosphorylated protein kinase B (p-Akt) in vivo and in vitro. Pre-treatment of H9c2 cells with SPF inhibited attenuation of nuclear factor (Nrf2) and heme oxygenase (HO-1). Hence, SPF could be used as a preventive and therapeutic plant ingredient against ATO-induced cardiotoxicity.
Databáze: OpenAIRE
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