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

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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

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.",

keywords = "Administration route, High-dose dextromethorphan, Myelinoid bodies with mitochondrial dysfunction",

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

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",

year = "2016",

month = oct,

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

language = "English",

volume = "132",

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journal = "Journal of Pharmacological Sciences",

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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

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.

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

Abstract

Keywords

ASJC Scopus subject areas

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