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Effect of parthanatos on ropivacaine‐induced damage in SH‐SY5Y cells
Author(s) -
Zheng Ting,
Zheng Chunying,
Zheng Xiaochun,
Zhao Ruoguang,
Chen Yanqing
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12730
Subject(s) - nad+ kinase , poly adp ribose polymerase , ropivacaine , nicotinamide adenine dinucleotide , intracellular , programmed cell death , apoptosis , nicotinamide , biology , chemistry , microbiology and biotechnology , biochemistry , pharmacology , polymerase , enzyme
Summary Ropivacaine is one of the most common but toxic local anaesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine‐induced neuronal injury model and research the effects of ropivacaine on PARP ‐1 activation and nicotinamide adenine dinucleotide ( NAD ) + depletion. The cell death and apoptosis of ropivacaine‐induced SH ‐ SY 5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD + level, and western blots were used to analyze the expression levels of PARP ‐1 and apoptosis‐inducing factor ( AIF ) after ropivacaine treatments with different concentrations and durations. A PARP ‐1 inhibitor ( PJ ‐34) was used to confirm the relationship between PARP ‐1 activation and NAD + depletion. Hoechst 33258 nuclear staining and a mitochondrial membrane potential (Δψm) assay were used to detect the role of exogenous NAD + in ropivacaine‐induced neuronal injury. Ropivacaine‐induced SH ‐ SY 5Y cell death and apoptosis, PARP ‐1 activation, and AIF increase as well as intracellular NAD + depletion occurred in a time‐ and concentration‐dependent manner ( P <.05). PARP ‐1 activation led to NAD + depletion ( P <.05). Exogenous NAD + impaired ropivacaine‐induced nuclear injury ( P <.05). Ropivacaine treatment induced PARP ‐1 activation and NAD + depletion ( P <.05). Parthanatos ( PARP ‐1‐dependent cell death) was definitely involved in ropivacaine‐induced neuronal injury, and exogenous NAD + may be a novel therapeutic method for parthanatos‐dependent neuronal injury.