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Cardiovascular Toxicology
Published in: Cardiovascular Toxicology 3/2019

01-06-2019

Methoxetamine Induces Cytotoxicity in H9c2 Cells: Possible Role of p21 Protein (Cdc42/Rac)-Activated Kinase 1

Authors: Kyung Sik Yoon, Sun Mi Gu, Santosh Lamichhane, Kyoung Moon Han, Jisoon Shin, Young-Hoon Kim, Soo Kyung Suh, Hye Jin Cha, Jaesuk Yun

Published in: Cardiovascular Toxicology | Issue 3/2019

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Abstract

The abuse of new psychoactive substances (NPS) is an emerging social problem. Methoxetamine, one of the NPS, was designed as an alternative to ketamine and it was considered an NPS candidate owing to its high addictive potential. However, cardiotoxicity of the phencyclidine analogue, methoxetamine, has not been extensively evaluated. P21 protein (Cdc42/Rac)-activated kinase 1 (PAK-1) is associated with the drug-induced cardiotoxicity and hypertrophy of cardiomyocytes. In the present study, we investigated the effects of methoxetamine on rat cardiomyocytes and PAK-1. Methoxetamine (at 10 µM) reduced cell viability and PAK-1 mRNA levels in H9c2 cells. Methoxetamine treatment (100 µM) decreased the beating rate of primary cardiomyocytes. However, 100 µM methoxetamine-induced heart rate decline was less than 100 µM PCP- or ketamine-induced heart rate decline. Meanwhile, fingolimod hydrochloride (FTY720, 1 µM), a PAK-1 activator, increased cell viability and inhibited hypertrophy induced by methoxetamine in H9c2 cells. These results suggest that methoxetamine may have harmful effects on the cardiovascular system through the regulation of the expression and function of PAK-1.
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Metadata
Title
Methoxetamine Induces Cytotoxicity in H9c2 Cells: Possible Role of p21 Protein (Cdc42/Rac)-Activated Kinase 1
Authors
Kyung Sik Yoon
Sun Mi Gu
Santosh Lamichhane
Kyoung Moon Han
Jisoon Shin
Young-Hoon Kim
Soo Kyung Suh
Hye Jin Cha
Jaesuk Yun
Publication date
01-06-2019
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 3/2019
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-018-9489-4

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