Troxerutin attenuates oxygenglucose deprivation and reoxygenationinduced oxidative stress and inflammation by enhancing the PI3K/AKT/HIF1α signaling pathway in H9C2 cardiomyocytes.
Mol Med Rep
; 22(2): 1351-1361, 2020 08.
Article
de En
| MEDLINE
| ID: mdl-32626962
ABSTRACT
Myocardial ischemiareperfusion (MI/R) injury is a complex pathological process that occurs when tissues are reperfused following a prolonged period of ischemia. Troxerutin has been reported to have cardioprotective functions. However, the underlying mechanism by which troxerutin protects against MI/R injury has not been fully elucidated. The aim of the present study was to explore whether troxerutinmediated protection against oxygenglucose deprivation/reoxygenation (OGD/R)induced H9C2 cell injury was associated with the inhibition of oxidative stress and the inflammatory response by regulating the PI3K/AKT/hypoxiainducible factor1α (HIF1α) signaling pathway. The results of the present study suggested that troxerutin pretreatment prevented the OGD/Rinduced reduction in cell viability, and the increase in lactate dehydrogenase activity and apoptosis. Troxerutin reversed OGD/Rinduced the inhibition of the PI3K/AKT/HIF1α signaling pathway as demonstrated by the increased expression of PI3K and HIF1α, and the increased ratio of phosphorylated AKT/AKT. LY294002, a selective PI3K inhibitor, inhibited the PI3K/AKT/HIF1α signaling pathway and further attenuated the protective effect of troxerutin against OGD/Rinduced H9C2 cell damage. Furthermore, small interfering (si)RNAmediated knockdown of HIF1α reduced troxerutininduced protection against OGD/R injury. Troxerutin pretreatment alleviated OGD/Rinduced oxidative stress, as demonstrated by the reduced generation of reactive oxygen species and malonaldehyde content, and the increased activities of superoxide dismutase and glutathione peroxidase, which were reduced by HIF1αsiRNA. Troxerutininduced decreases in the levels of interleukin (IL)1ß, IL6 and tumor necrosis factorα in OGD/R conditions were also reduced by HIF1αsiRNA. The results from the present study indicated that troxerutin aggravated OGD/Rinduced H9C2 cell injury by inhibiting oxidative stress and the inflammatory response. The primary underlying protective mechanism of troxerutin was mediated by the activation of the PI3K/AKT/HIF1α signaling pathway.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cardiotoniques
/
Transduction du signal
/
Survie cellulaire
/
Stress oxydatif
/
Myocytes cardiaques
/
O-(bêta-Hydroxyéthyl)rutosides
Limites:
Animals
Langue:
En
Journal:
Mol Med Rep
Année:
2020
Type de document:
Article