title: In vivo and in vitro evidence of the neurotoxic effects of ropivacaine: the role of the Akt signaling pathway.
abstract: There is a growing body of evidence that suggests common complications in             regional anesthesia, including transient neurological syndrome, are caused by             the neurotoxicity of local anesthetics (LAs). Ropivacaine is thought to be one             of the safest LAs, however, there have been several studies detailing possible             neurotoxic effects. At present, the exact molecular mechanism of ropivacaine-mediated             neurotoxicity is unknown. The present study was designed to explore the possible             mechanisms underlying the neurotoxicity of ropivacaine. The neurotoxic effects             of ropivacaine were assessed in spinal cord by TUNEL staining for apoptosis and             in cultured PC12 cells by cell viability assays. Protein kinase B (Akt) activation             was evaluated by immunoblotting. Ropivacaine promoted apoptosis and caused cell             death in a treatment group compared with a sham-operated group. Furthermore, ropivacaine             significantly diminished Akt activation. There were significantly lower Akt levels             in cells exposed to ropivacaine compared with controls. The present study demonstrated             ropivacaine neurotoxicity in vivo and in vitro, mediated by the Akt signaling             pathway. The neurotoxicity of apoptosis with concomitant cell death, mediated             by ropivacaine, may offer an explanation for its adverse effects (e.g., transient             neurological syndrome).
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South                     University, Changsha 410008, P.R. China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sun
authors.forename: Huining
authors.initials: H
authors.lastname: Liu
authors.forename: Qulian
authors.initials: Q
authors.lastname: Guo
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Wang
mesh_terms: D000577:Amides / Q000633:toxicity*; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D008297:Male; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D051057:Proto-Oncogene Proteins c-akt