Dexmedetomidine attenuates hepatic ischemia-reperfusion injury-induced apoptosis via reducing oxidative stress and endoplasmic reticulum stress.

Dexmedetomidine (DEX) affords a hepatoprotective effect during ischemia-reperfusion (IR) injury (IRI); however, the underlying mechanism remains elusive. In this work, using a rat liver IR model and a BRL-3A cell hypoxia-reoxygenation (HR) model, we explored whether DEX protects the liver against IRI by decreasing oxidative stress (OS), endoplasmic reticulum stress (ERS), and apoptotic pathways. We found that DEX significantly increased SOD and GSH activity while decreasing ROS and MDA levels in BRL-3A cells, successfully preventing HR-induced OS damage. DEX administration reduced JNK, ERK, and P38 phosphorylation and blocked HR-induced MAPK signaling pathway activation. Additionally, DEX administration reduced the expression of GRP78, IRE1α, XBP1, TRAF2, and CHOP, which reduced HR-induced ERS. NAC prevented the MAPK pathway from being activated and inhibited the ERS pathway. Further research showed that DEX significantly reduced HR-induced apoptosis by suppressing the expression of Bax/Bcl-2 and cleaved caspase-3. Similarly, animal studies demonstrated DEX exerted a protective effect of the liver by alleviating histopathological injury and enhancing liver function, mechanically DEX reduced cell apoptosis in liver tissue by reducing oxidative stress and ERS. In conclusion, DEX mitigates OS and ERS during IR, thereby suppressing cell apoptosis, thus providing protection to the liver.