Celastrol pretreatment attenuates rat myocardial ischemia/ reperfusion injury by inhibiting high mobility group box 1 protein expression via the PI3K/Akt pathway.

Biochemical and Biophysical Research Communications
Suiyang TongXuejun Jiang

Abstract

Celastrol pretreatment has been shown to protect against myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism is poorly understood. This study aimed to investigate the cardioprotective effects of celastrol pretreatment on I/R injury and to further explore whether its mechanism of action was associated with the inhibition of high mobility group box 1 protein (HMGB1) expression via the phosphoinositide 3-kinase (PI3K)/Akt pathway. In a fixed-dose study, hematoxylin and eosin staining and myocardial enzyme measurements were used to determine the optimal dose of celastrol that elicited the best cardioprotective effects against I/R injury. Furthermore, rats were pretreated with 4 mg/kg celastrol, and infarct size and the levels of myocardial enzymes, apoptosis, inflammatory and oxidative indices, and HMGB1 and p-Akt expression were measured. Our results indicated that celastrol dose-dependently attenuated histopathological changes and the elevation in myocardial enzymes induced by I/R. Moreover, the celastrol pretreatment (4 mg/kg) not only significantly decreased infarct size as well as myocardial enzyme levels but also inhibited myocardial apoptosis, inflammatory response and oxidative stress. Additionally, c...Continue Reading

Citations

Aug 16, 2019·Drug and Chemical Toxicology·Ramin RezaeeMahmoud Hashemzaei
Aug 23, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Hanyu ShiHaiqing Gao
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