Cardioprotective effects of dihydroquercetin against ischemia reperfusion injury by inhibiting oxidative stress and endoplasmic reticulum stress-induced apoptosis via the PI3K/Akt pathway

2019 ◽  
Vol 10 (1) ◽  
pp. 203-215 ◽  
Author(s):  
Zunpeng Shu ◽  
Yanni Yang ◽  
Liu Yang ◽  
Hai Jiang ◽  
Xiaojin Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Endoplasmic Reticulum ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Akt Pathway ◽  
Prevention And Treatment ◽  
Cardioprotective Effects ◽  
Induced Apoptosis

Dihydroquercetin (DHQ), a dihydroxyflavone, possesses potent antioxidant properties and is proposed to be useful in the prevention and treatment of cardiovascular disease.

Abstract MP58: Tissue And Sex Specific Effects Of Gstm1 Deletion In Mouse Models

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yves Wang ◽  
Nhu Nguyen ◽  
Keith Nehrke ◽  
Paul S Brookes ◽  
Thu H Le
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Properties ◽  
Iri Model ◽  
Increased Risk ◽  
Study Gene Expression

The glutathione S-transferase ( Gst ) gene family encodes antioxidant enzymes. In humans, a common null allele deletion variant of GST μ-1 ( GSTM1 ) is highly prevalent across populations and is associated with increased risk and progression of various diseases. Using a Gstm1 knockout (KO) mouse model, we previously showed that KO mice with angiotensin II-induced hypertension (HTN) have increased kidney injury compared to wild-type (WT) controls, mediated by elevated oxidative stress. In the same mouse model, we have recently reported that in a Langendorff-perfused cardiac ischemia-reperfusion injury (IRI) model, where damage is also mediated by oxidative stress, male KO hearts are protected while females are not. Here, we investigated the molecular mechanisms for this difference in male hearts. WT and KO mice of both sexes were studied at 12-20 weeks of age. Hearts were snap frozen at baseline and after 25 min of global ischemia, and kidneys were collected at baseline and 4 weeks following HTN induction. A panel of 18 Gst genes were probed by qPCR from baseline hearts and kidneys of both sexes. Global metabolites were assayed using Metabolon, Inc. from hearts of both sexes and kidneys of males, at both baseline and diseased states. Analysis by qPCR (n = 3/group) showed that male, but not female, KO hearts had upregulation of other Gst s. In contrast, no significant differences between were found in male kidneys. Metabolomics (n = 6/group) detected 695 metabolites in hearts and 926 in kidneys. There were increases in several metabolites in KO vs. WT hearts including those with antioxidant properties. Notably, increases in carnosine and anserine were observed in KO male hearts but not in female hearts, while that of other antioxidant-related metabolites were observed in hearts of both sexes, but not in kidneys. HTN induced significant increases in metabolites in KO vs. WT kidneys in the pathways related to and linking methionine, cysteine, and glutathione, which were not observed in hearts. In this study, gene expression and metabolites suggest that the mechanisms compensating for the loss of GSTM1 are both tissue and sex specific. The resulting differences in antioxidant enzymes and metabolites may explain the unexpected protection for male Gstm1 KO hearts in IRI.

scholarly journals Tubeimoside I Ameliorates Myocardial Ischemia-Reperfusion Injury through SIRT3-Dependent Regulation of Oxidative Stress and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Dingyi Lv ◽  
Minghao Luo ◽  
Zhe Cheng ◽  
Ruiyu Wang ◽  
Xiyang Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Tubeimoside I ◽  
Expression And Activity

Myocardial ischemia-reperfusion injury (MIRI) is a phenomenon that reperfusion leads to irreversible damage to the myocardium and increases mortality in acute myocardial infarction (AMI) patients. There is no effective drug to treat MIRI. Tubeimoside I (TBM) is a triterpenoid saponin purified from Chinese traditional medicine tubeimu. In this study, 4 mg/kg TBM was given to mice intraperitoneally at 15 min after ischemia. And TBM treatment improved postischemic cardiac function, decreased infarct size, diminished lactate dehydrogenase release, ameliorated oxidative stress, and reduced apoptotic index. Notably, ischemia-reperfusion induced a significant decrease in cardiac SIRT3 expression and activity, while TBM treatment upregulated SIRT3’s expression and activity. However, the cardioprotective effects of TBM were largely abolished by a SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). This suggests that SIRT3 plays an essential role in TBM’s cardioprotective effects. In vitro, TBM also protected H9c2 cells against simulated ischemia/reperfusion (SIR) injury by attenuating oxidative stress and apoptosis, and siSIRT3 diminished its protective effects. Taken together, our results demonstrate for the first time that TBM protects against MIRI through SIRT3-dependent regulation of oxidative stress and apoptosis. TBM might be a potential drug candidate for MIRI treatment.

Sign in / Sign up

Export Citation Format

Share Document