Schisandra fructus extract ameliorates doxorubicin-induce cytotoxicity in cardiomyocytes: altered gene expression for detoxification enzymes.
The effect of Schisandra fructus extract (SFE) on doxorubicin (Dox)-induced cardiotoxicity was investigated in H9c2 cardiomyocytes. Dox, which is an antineoplastic drug known to induce cardiomyopathy possibly through production of reactive oxygen species, induced significant cytotoxicity, intracellular reactive oxygen species (ROS), and lipid peroxidation. SFE treatment significantly increased cell survival up to 25%, inhibited intracellular ROS production in a time- and dose-dependent manner, and inhibited lipid peroxidation induced by Dox. In addition, SFE treatment induced expression of cellular glutathione S-transferases (GSTs), which function in the detoxification of xenobiotics, and endogenous toxicants including lipid peoxides. Analyses of 31,100 genes using Affymetrix cDNA microarrays showed that SFE treatment up-regulated expression of genes involved in glutathione metabolism and detoxification [GST theta 1, mu 1, and alpha type 2, heme oxygenase 1 (HO-1), and microsomal epoxide hydrolase (mEH)] and energy metabolism [carnitine palmitoyltransferase-1 (CPT-1), transaldolase, and transketolase]. These data indicated that SFE might increase the resistance to cardiac cell injury by Dox, at least partly, together with altering gene expression, especially induction of phase II detoxification enzymes.
Choi
Eun Hye
EH
Food Safety Research Center, Korea Food Research Institute, 516, Backhyun, Bundang-gu, Sungnam, Kyonggi-do, 463-746, South Korea.
Lee
Nari
N
Kim
Hyun Jung
HJ
Kim
Mi Kyung
MK
Chi
Sung-Gil
SG
Kwon
Dae Young
DY
Chun
Hyang Sook
HS