Diallyl trisulfide suppresses doxorubicin-induced cardiomyocyte apoptosis by inhibiting MAPK/NF-κB signaling through attenuation of ROS generation

Environmental Toxicology
Su-Ying WenWei-Wen Kuo

Abstract

Doxorubicin (Dox) is an effective anticancer agent. However, its effectiveness is limited by its cardiotoxic effects. It has also been reported that the mitogen-activated protein kinase family and NF-κB can be activated by Dox treatment. DATS has been shown to be a potent antioxidant with cardioprotective effects. We investigate whether Dox induces cardiac apoptosis through JNK- and ERK-dependent NF-κB upregulation that can be reduced by DATS treatment. H9c2 cells were treated with 0.5-1.5 μM Dox for 24 hours. Dox promoted apoptosis and ROS generation and inhibited viability in a dose-dependent manner. Then, the phosphorylation levels of JNK, ERK, and NF-κB evaluated by western blot were elevated. We used inhibitors of JNK, ERK, and NF-κB to determine which of these proteins were involved in Dox-induced apoptosis. Furthermore, Dox-exposed cells were treated with DATS at doses of 1, 5, and 10 μM, and the data demonstrated that ROS generation and apoptotic proteins were decreased and that ERK and NF-κB were downregulated in a dose-dependent manner. Additionally, six-week-old rats were divided into three groups (n = 6 per group) designed as an eight-week study. Normal, Dox (at dose 3.75 mg/kg by ip) administered with or without DA...Continue Reading

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Citations

Apr 12, 2018·Journal of Cardiovascular Pharmacology·Hai-Bing YangZhao-Yang Lu
Jun 30, 2018·Cancer Biotherapy & Radiopharmaceuticals·Wenjing YuRongyang Dai
May 10, 2019·Chemical Communications : Chem Comm·Hong YaoShengtao Xu
Sep 24, 2019·Journal of Microencapsulation·Jing SunJing Wu
Mar 9, 2021·Technology and Health Care : Official Journal of the European Society for Engineering and Medicine·Yaling LiJun Yang
Nov 4, 2020·Journal of Agricultural and Food Chemistry·Jinxin XieRi-Yuan Tang
Dec 29, 2021·Phytotherapy Research : PTR·Farhad EisvandHossein Hosseinzadeh

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