PMID- 29382532 OWN - NLM STAT- MEDLINE DCOM- 20181009 LR - 20181009 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 827 DP - 2018 May 15 TI - Cordycepin rescues lidocaine-induced neurotoxicity in dorsal root ganglion by interacting with inflammatory signaling pathway MMP3. PG - 88-93 LID - S0014-2999(18)30062-1 [pii] LID - 10.1016/j.ejphar.2018.01.049 [doi] AB - Application of local anesthetic reagents, such as lidocaine (Lid), could cause significant neurotoxicity in spinal cord dorsal root ganglia neurons (DRGNs). In this study, we investigated the potential rescuing effect of cordycepin (CDC) in an in vitro explant model of lidocaine-induced apoptosis in DRGNs. Explant of rat neonatal DRGNs was prepared, and treated with Lid in vitro to induce neuronal apoptosis. Prior to Lid treatment, DRGN explant was pre-incubated with various concentrations of CDC to evaluate its rescuing effect on Lid-induced apoptosis. We found that, in cultured DRGNs, Lid caused significant neuronal apoptosis whereas pre-incubation of CDC rescued Lid-induced neurotoxicity. In addition, gene and protein expressions of Caspase-9 and Matrix metalloproteinase 3 (MMP3), a key component of inflammatory signal pathway, were both upregulated by Lid but downregulated by CDC pre-incubation. We further overexpressed MMP3 in cultured DRGNs. And discovered that forced MMP3 overexpression upregulated endogenous MMP3 and caspase-9, and reversed the rescuing effect of CDC on Lid-induced neurotoxicity in DRGNs. Therefore, we concluded that CDC has protective effect on local anesthesia induced spinal cord neurotoxicity, possibly through the inverse regulation on inflammatory signaling pathway. CI - Copyright (c) 2018. Published by Elsevier B.V. FAU - Kan, Hongli AU - Kan H AD - Department of Anesthesia, Cancer Hospital of Jilin Province, Changchun 130012, China. FAU - Wang, Yang AU - Wang Y AD - Department of Interventional Therapy, Jilin Provincial People's Hospital, Changchun 130021, China. Electronic address: ericwang22@aol.com. FAU - Wang, Dongxin AU - Wang D AD - Department of Anesthesia, Cancer Hospital of Jilin Province, Changchun 130012, China. FAU - Sun, Hong AU - Sun H AD - Department of Anesthesia, Cancer Hospital of Jilin Province, Changchun 130012, China. FAU - Zhou, Shu AU - Zhou S AD - Department of Anesthesia, Cancer Hospital of Jilin Province, Changchun 130012, China. FAU - Wang, Huaiwu AU - Wang H AD - Department of Anesthesia, Cancer Hospital of Jilin Province, Changchun 130012, China. FAU - Guan, Jian AU - Guan J AD - Department of Anesthesia, Cancer Hospital of Jilin Province, Changchun 130012, China. FAU - Li, Ming AU - Li M AD - Department of Anesthesia, Cancer Hospital of Jilin Province, Changchun 130012, China. LA - eng PT - Journal Article DEP - 20180131 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Deoxyadenosines) RN - 98PI200987 (Lidocaine) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - GZ8VF4M2J8 (cordycepin) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Deoxyadenosines/*pharmacology MH - Down-Regulation/drug effects MH - Ganglia, Spinal/*pathology MH - Gene Expression Regulation, Enzymologic/drug effects MH - Inflammation/pathology MH - Lidocaine/*toxicity MH - Matrix Metalloproteinase 3/genetics/*metabolism MH - Neurons/*drug effects/pathology MH - Rats MH - Signal Transduction/*drug effects OTO - NOTNLM OT - Anesthesia OT - Cordycepin OT - Dorsal root ganglion neuron OT - Lidocaine OT - MMP3 OT - Spinal cord EDAT- 2018/02/01 06:00 MHDA- 2018/10/10 06:00 CRDT- 2018/02/01 06:00 PHST- 2017/11/27 00:00 [received] PHST- 2018/01/23 00:00 [revised] PHST- 2018/01/26 00:00 [accepted] PHST- 2018/02/01 06:00 [pubmed] PHST- 2018/10/10 06:00 [medline] PHST- 2018/02/01 06:00 [entrez] AID - S0014-2999(18)30062-1 [pii] AID - 10.1016/j.ejphar.2018.01.049 [doi] PST - ppublish SO - Eur J Pharmacol. 2018 May 15;827:88-93. doi: 10.1016/j.ejphar.2018.01.049. Epub 2018 Jan 31.