High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats

Hai Quyen Tran; Yoon Hee Chung; Eun Joo Shin; Won Ki Kim; Jae Chul Lee; Ji Hoon Jeong; Myung Bok Wie; Choon Gon Jang; Kiyofumi Yamada; Toshitaka Nabeshima; Hyoung Chun Kim

doi:10.1016/j.jphs.2016.10.001

High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats

Hai Quyen Tran, Yoon Hee Chung, Eun Joo Shin, Won Ki Kim, Jae Chul Lee, Ji Hoon Jeong, Myung Bok Wie, Choon Gon Jang, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung Chun Kim

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4 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	166-170
Number of pages	5
Journal	Journal of Pharmacological Sciences
Volume	132
Issue number	2
DOIs	https://doi.org/10.1016/j.jphs.2016.10.001
Publication status	Published - 2016 Oct 1

Bibliographical note

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

Keywords

Administration route
High-dose dextromethorphan
Myelinoid bodies with mitochondrial dysfunction

ASJC Scopus subject areas

Molecular Medicine
Pharmacology

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10.1016/j.jphs.2016.10.001

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title = "High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats",

abstract = "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.",

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note = "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: {\textcopyright} 2016 The Authors",

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doi = "10.1016/j.jphs.2016.10.001",

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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

PY - 2016/10/1

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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.

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High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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