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Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion
BACKGROUND: The CD38/cyclic ADP-ribose (cADPR) pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convuls...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634088/ https://www.ncbi.nlm.nih.gov/pubmed/28937043 http://dx.doi.org/10.4103/0366-6999.215333 |
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author | Zou, Yu He, Xin Peng, Qian-Yi Guo, Qu-Lian |
author_facet | Zou, Yu He, Xin Peng, Qian-Yi Guo, Qu-Lian |
author_sort | Zou, Yu |
collection | PubMed |
description | BACKGROUND: The CD38/cyclic ADP-ribose (cADPR) pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion. METHODS: Forty male Sprague-Dawley rats were randomly divided into five groups (n = 8 per group): sham group, ropivacaine group, ropivacaine+8-Br-cADPR (5 nmol) group, ropivacaine+8-Br-cADPR (10 nmol) group, and ropivacaine+8-Br-cADPR (20 nmol) group (no rats died). Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde (MDA) and superoxide dismutase (SOD) assays. RESULTS: Intraperitoneal injection of ropivacaine (33.8 mg/kg) induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion (P = 0.031 and 0.020, respectively, compared with the sham group). Intraventricular injection of 8-Br-cADPR (5, 10, and 20 nmol) significantly prolonged convulsion latency (P = 0.037, 0.034, and 0.000, respectively), reduced convulsion duration (P = 0.005, 0.005, and 0.005, respectively), and reduced convulsion behavior scores (P = 0.015, 0.015, and 0.000, respectively). Intraventricular injection of 8-Br-cADPR (10 nmol) also increased the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio (P = 0.044) and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDA and SOD levels (P = 0.014, 0.044, 0.001, and 0.010, respectively) compared with the ropivacaine group. CONCLUSIONS: The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress. |
format | Online Article Text |
id | pubmed-5634088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-56340882017-10-11 Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion Zou, Yu He, Xin Peng, Qian-Yi Guo, Qu-Lian Chin Med J (Engl) Original Article BACKGROUND: The CD38/cyclic ADP-ribose (cADPR) pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion. METHODS: Forty male Sprague-Dawley rats were randomly divided into five groups (n = 8 per group): sham group, ropivacaine group, ropivacaine+8-Br-cADPR (5 nmol) group, ropivacaine+8-Br-cADPR (10 nmol) group, and ropivacaine+8-Br-cADPR (20 nmol) group (no rats died). Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde (MDA) and superoxide dismutase (SOD) assays. RESULTS: Intraperitoneal injection of ropivacaine (33.8 mg/kg) induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion (P = 0.031 and 0.020, respectively, compared with the sham group). Intraventricular injection of 8-Br-cADPR (5, 10, and 20 nmol) significantly prolonged convulsion latency (P = 0.037, 0.034, and 0.000, respectively), reduced convulsion duration (P = 0.005, 0.005, and 0.005, respectively), and reduced convulsion behavior scores (P = 0.015, 0.015, and 0.000, respectively). Intraventricular injection of 8-Br-cADPR (10 nmol) also increased the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio (P = 0.044) and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDA and SOD levels (P = 0.014, 0.044, 0.001, and 0.010, respectively) compared with the ropivacaine group. CONCLUSIONS: The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress. Medknow Publications & Media Pvt Ltd 2017-10-05 /pmc/articles/PMC5634088/ /pubmed/28937043 http://dx.doi.org/10.4103/0366-6999.215333 Text en Copyright: © 2017 Chinese Medical Journal http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Zou, Yu He, Xin Peng, Qian-Yi Guo, Qu-Lian Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion |
title | Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion |
title_full | Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion |
title_fullStr | Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion |
title_full_unstemmed | Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion |
title_short | Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion |
title_sort | inhibition of cd38/cyclic adp-ribose pathway protects rats against ropivacaine-induced convulsion |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634088/ https://www.ncbi.nlm.nih.gov/pubmed/28937043 http://dx.doi.org/10.4103/0366-6999.215333 |
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