Naringin protects cardiomyocytes against hyperglycemia-induced injuries in vitro and in vivo.
We previously reported that naringin (NRG) protects cardiomyocytes against high glucose (HG)-induced injuries by inhibiting the MAPK pathway. The aim of this study was to test the hypothesis that NRG prevents cardiomyocytes from hyperglycemia-induced insult through the inhibition of the nuclear factor kappa B (NF-κB) pathway and the upregulation of ATP-sensitive K(+) (KATP) channels. Our results showed that exposure of cardiomyocytes to HG for 24h markedly induced injuries, as evidenced by a decrease in cell viability and oxidative stress, and increases in apoptotic cells as well as the dissipation of mitochondrial membrane potential (MMP). These injuries were markedly attenuated by the pretreatment of cells with either NRG or pyrrolidine dithiocarbamate (PDTC) before exposure to HG. Furthermore, in streptozotocin (STZ)-induced diabetic rats and in HG-induced cardiomyocytes, the expression levels of caspase-3, bax and phosphorylated (p)-NF-κB p65 were increased. The increased protein levels were ameliorated by pretreatment with both NRG and PDTC. However, the expression levels of bcl-2 and KATP and superoxide dismutase (SOD) activity were decreased by hyperglycemia; the expression level of Nox4 and the ADP/ATP ratio were increased by hyperglycemia. These hyperglycemia-induced indexes were inhibited by the pretreatment of cardiomyocytes with NRG or PDTC. In addition, in STZ-induced diabetic rats, we also observed that NRG or PDTC contributed to protecting mitochondrial injury and myocardium damage. This study demonstrated that NRG protects cardiomyocytes against hyperglycemia-induced injury by upregulating KATP channels in vitro and inhibiting the NF-κB pathway in vivo and in vitro.
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China.
Qiong
Q
You
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China.
Zijun
Z
Wu
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China.
Bin
B
Wu
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China.
Chang
C
Liu
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China.
Ruina
R
Huang
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China.
Li
L
Yang
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China.
Runmin
R
Guo
Department of CardiovasologyThe Affiliated Hospital, Guangdong Medical College, Guangdong, Zhanjiang, China wukeng1245@hotmail.com chenjf-sums@hotmail.com.
Keng
K
Wu
Department of CardiologyThe Third People's Hospital of Dongguan City, Cardiovascular Institute of Dongguan City, Dongguan, Guangdong, China wukeng1245@hotmail.com chenjf-sums@hotmail.com.
Jingfu
J
Chen
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000517:prevention & control*; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009206:Myocardium / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018384:Oxidative Stress; D011759:Pyrrolidines; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates; D051996:Transcription Factor RelA / Q000378:metabolism*
D044950:Flavanones; D054086:KATP Channels; D011759:Pyrrolidines; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D020782:Matrix Metalloproteinases; C005273:naringenin
ATP-sensitive K+ channels; cardiomyocytes; cardioprotection; hyperglycemia; naringin; nuclear factor kappa B pathway