TY - JOUR
T1 - High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats
AU - Tran, Hai Quyen
AU - Chung, Yoon Hee
AU - Shin, Eun Joo
AU - Kim, Won Ki
AU - Lee, Jae Chul
AU - Jeong, Ji Hoon
AU - Wie, Myung Bok
AU - Jang, Choon Gon
AU - Yamada, Kiyofumi
AU - Nabeshima, Toshitaka
AU - Kim, Hyoung Chun
N1 - Funding Information:
This study was supported by a grant ( 14182MFDS979 ) from the Korea Food and Drug Administration, Republic of Korea . Hai-Quyen Tran was supported by the BK21 PLUS program, National Research Foundation of Korea, Republic of Korea . Equipment at the Institute of New Drug Development Research (Kangwon National University) was used for this study.
Publisher Copyright:
© 2016 The Authors
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed.
AB - Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed.
KW - Administration route
KW - High-dose dextromethorphan
KW - Myelinoid bodies with mitochondrial dysfunction
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U2 - 10.1016/j.jphs.2016.10.001
DO - 10.1016/j.jphs.2016.10.001
M3 - Article
C2 - 27802908
AN - SCOPUS:84994415921
VL - 132
SP - 166
EP - 170
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 2
ER -