Abstract
We previously demonstrated that baicalein could protect against liver ischemia/reperfusion (I/R) injury in mice. The exact mechanism of baicalein remains poorly understood. Autophagy plays an important role in protecting against I/R injury. This study was designed to determine whether baicalein could protect against liver I/R injury via induction of autophagy in rats. Baicalein was intraperitoneally injected 1 h before warm ischemia. Pretreatment with baicalein prior to I/R insult significantly blunted I/R-induced elevations of serum aminotransferase levels and significantly improved the histological status of livers. Electron microscopy and expression of the autophagic marker LC3B-II suggested induction of autophagy after baicalein treatment. Moreover, inhibition of the baicalein-induced autophagy using 3-methyladenine (3-MA) worsened liver injury. Furthermore, baicalein treatment increased heme oxygenase (HO)-1 expression, and pharmacological inhibition of HO-1 with tin protoporphyrin IX (SnPP) abolished the baicalein-mediated autophagy and the hepatocellular protection. In primary rat hepatocytes, baicalein-induced autophagy also protected hepatocytes from hypoxia/reoxygenation injury in vitro and the beneficial effect was abrogated by 3-MA or Atg7 siRNA, respectively. Suppression of HO-1 activity by SnPP or HO-1 siRNA prevented the baicalein-mediated autophagy and resulted in increased hepatocellular injury. Collectively, these results suggest that baicalein prevents hepatocellular injury via induction of HO-1-mediated autophagy.
Highlights
A protective mechanism during hepatic I/R injury, and induction of autophagy has emerged as a new potential strategy to ameliorate liver function after I/R injury[14,15,16,17,18,19]
Liver damage was assessed by measuring serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels, which were markedly increased at 1 h and 6 h after I/R injury compared with those in the sham group
Recent studies have demonstrated that baicalein has a beneficial effect in liver injury caused by toxic[5,6,7], D-galactosamine/LPS4 and sepsis[24]
Summary
A protective mechanism during hepatic I/R injury, and induction of autophagy has emerged as a new potential strategy to ameliorate liver function after I/R injury[14,15,16,17,18,19]. The role of autophagy in baicalein-afforded protection and the potential mechanisms involved are not fully understood. HO-1 has been shown to confer protection in liver I/R injury by modulating oxidative stress and inflammation[20,21]. Recent studies show that in addition to these actions, HO-1 attenuates liver I/R injury by induction of autophagy[22,23]. It is unclear whether HO-1 mediated autophagy is a mechanism by which baicalein protects against liver I/R injury. The aim of this study was to evaluate whether autophagy is an essential mediator in baicalein-afforded protection and to further explore the role of HO-1 in autophagy
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