caa a22 4500 445374721 CHVBK 20180317142959.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s00540-010-1079-y doi (NATIONALLICENCE)springer-10.1007/s00540-010-1079-y Lidocaine depolarizes the mitochondrial membrane potential by intracellular alkalization in rat dorsal root ganglion neurons [Elektronische Daten] [Shin Onizuka, Tetsu Yonaha, Ryuji Tamura, Masatoshi Kasiwada, Toshiro Shirasaka, Isao Tsuneyoshi] Purpose: The mitochondrial membrane potential (ΔΨm) is an important factor for apoptosis, and it is produced by the proton electrochemical gradient (ΔµH+). Therefore, the intracellular proton concentration (pHin) is an important factor for modifying the ΔΨm. However, the effects of lidocaine on pHin are unclear. To investigate mitochondrial responses to lidocaine, therefore, we simultaneously measured pHin with ΔΨm, flavin adenine dinucleotide (FAD), and reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence, and calculated the FAD/NADH ratio (redox ratio), the superoxide production in mitochondria. Methods: Morphological change and early apoptosis were observed by annexin-V FITC staining under fluorescent microscope. The ratiometric fluorescent probe JC-1 and HPTS were used for the simultaneous measurements of ΔΨm with pHin in rat dorsal root ganglion (DRG) neurons. FAD and NADH autofluorescence were simultaneously measured, and the FAD/NADH fluorescence ratio (redox ratio) was calculated. The superoxide was measured by mitosox-red fluorescent probe for mitochondrial superoxide. Lidocaine was evaluated at 1, 5, and 10mM. Results: Morphological change and early apoptosis were observed after 10mM lidocaine administration. Lidocaine depolarized ΔΨm with increased pHin in a dose-dependent manner. In low-pH saline (pH 6), in the presence of both the weak acids (acetate and propionate), lidocaine failed to depolarize ΔΨm and increase pHin. On the other hand, lidocaine decreased the redox ratio in the cell and increased the levels of superoxide in a dose-dependent manner. Conclusion: These results demonstrated that lidocaine depolarizes ΔΨm by intracellular alkalization. These results may indicate one of the mechanisms responsible for lidocaine-induced neurotoxicity. Japanese Society of Anesthesiologists, 2010 Lidocaine nationallicence Mitochondrial membrane potential nationallicence Intracellular alkalization nationallicence Onizuka Shin Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut Yonaha Tetsu Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut Tamura Ryuji Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut Kasiwada Masatoshi Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut Shirasaka Toshiro Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut Tsuneyoshi Isao Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut Journal of Anesthesia Springer Japan 25/2(2011-04-01), 229-239 0913-8668 25:2<229 2011 25 540 https://doi.org/10.1007/s00540-010-1079-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00540-010-1079-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Onizuka Shin Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 700 1- Yonaha Tetsu Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 700 1- Tamura Ryuji Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 700 1- Kasiwada Masatoshi Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 700 1- Shirasaka Toshiro Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 700 1- Tsuneyoshi Isao Department of Anesthesiology, Faculty of Medicine, University of Miyazaki, Kiyotake, 889-1692, Miyazaki, Japan aut NATIONALLICENCE 773 0- Journal of Anesthesia Springer Japan 25/2(2011-04-01), 229-239 0913-8668 25:2<229 2011 25 540 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer