Ropivacaine regulates the expression and function of heme oxygenase-1

Publication date: July 2018 Source:Biomedicine & Pharmacotherapy, Volume 103 Author(s): Xiangbiao Yan, Yu Li, Xuechang Han, Xu Dong, Yajie Zhang, Qunzhi Xing As a new generation of amide-type local anesthetics (LAs), ropivacaine has been widely used for pain management in clinical settings. Increasing evidence has shown that administration of ropivacaine causes cytotoxic effects and apoptosis. However, the underlying molecular mechanisms still need to be elucidated. In the current study, our results indicated that ropivacaine treatment caused a significant induction of heme oxygenase-1 (HO-1) at both the mRNA and protein levels in human SHSY5Y cells. Levels of HO-1 mRNA and protein peaked at 1 h and 18 h, respectively, in response to ropivacaine treatment. Additionally, ropivacaine treatment enhanced HO-1 activity in a dose-dependent manner. Interestingly, we found that ropivacaine treatment induced phosphorylation of p38. Blockage of p38 phosphorylation with its specific inhibitor SB203580 or by transfection with p38 siRNA restrained ropivacaine-stimulated HO-1 expression. Additionally, we found that ropivacaine treatment promoted nuclear translocation of Nrf2 and amplified ARE promoter activity. Silencing of Nrf2 abolished ropivacaine-induced HO-1 expression. Notably, we found that inhibition of HO-1 activity promoted ropivacaine-induced production of reactive oxygen species (ROS), deletion of reduced glutathione (GSH), and release of lactate dehydrogena...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research