Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway

S. T. Lee, T. T. Wu, P. Y. Yu, R. M. Chen

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Background. Ketamine is widely used as an i.v. anaesthetic agent and as a drug of abuse. Hepatocytes contribute to the metabolism of endogenous and exogenous substances. This study evaluated the toxic effects of S-(+)-ketamine and possible mechanisms using human hepatoma HepG2 cells as the experimental model. Methods. HepG2 cells were exposed to S-(+)-ketamine. Cell viability and the release of lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (GPT) were measured to determine the toxicity of S-(+)-ketamine to HepG2 cells. Cell morphology, DNA fragmentation, and apoptotic cells were analysed to evaluate the mechanism of S-(+)-ketamine-induced cell death. Amounts of Bax, an apoptotic protein, and cytochrome c in the cytoplasm or mitochondria were quantified by immunoblotting. Cellular adenosine triphosphate levels were analysed using a bioluminescence assay. Caspases-3, -9, and -6 were measured fluorometrically. Results. Exposure of HepG2 cells to S-(+)-ketamine increased the release of LDH and GPT, but decreased cell viability (all P

Original languageEnglish
Pages (from-to)80-89
Number of pages10
JournalBritish Journal of Anaesthesia
Volume102
Issue number1
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Hep G2 Cells
Ketamine
Caspases
Mitochondria
Peptide Hydrolases
gamma-Glutamyltransferase
L-Lactate Dehydrogenase
Cell Survival
bcl-2-Associated X Protein
Caspase 9
Poisons
Street Drugs
DNA Fragmentation
Cytochromes c
Immunoblotting
Caspase 3
Anesthetics
Hepatocytes
Hepatocellular Carcinoma
Cytoplasm

Keywords

  • Anaesthetics i.v., ketamine
  • Liver, hepatotoxicity
  • Metabolism, ATP, DNA
  • Theories of anaesthetic action, cellular mechanisms

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway. / Lee, S. T.; Wu, T. T.; Yu, P. Y.; Chen, R. M.

In: British Journal of Anaesthesia, Vol. 102, No. 1, 01.2009, p. 80-89.

Research output: Contribution to journalArticle

@article{cd342a30573a488cab1205c77eccd159,
title = "Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway",
abstract = "Background. Ketamine is widely used as an i.v. anaesthetic agent and as a drug of abuse. Hepatocytes contribute to the metabolism of endogenous and exogenous substances. This study evaluated the toxic effects of S-(+)-ketamine and possible mechanisms using human hepatoma HepG2 cells as the experimental model. Methods. HepG2 cells were exposed to S-(+)-ketamine. Cell viability and the release of lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (GPT) were measured to determine the toxicity of S-(+)-ketamine to HepG2 cells. Cell morphology, DNA fragmentation, and apoptotic cells were analysed to evaluate the mechanism of S-(+)-ketamine-induced cell death. Amounts of Bax, an apoptotic protein, and cytochrome c in the cytoplasm or mitochondria were quantified by immunoblotting. Cellular adenosine triphosphate levels were analysed using a bioluminescence assay. Caspases-3, -9, and -6 were measured fluorometrically. Results. Exposure of HepG2 cells to S-(+)-ketamine increased the release of LDH and GPT, but decreased cell viability (all P",
keywords = "Anaesthetics i.v., ketamine, Liver, hepatotoxicity, Metabolism, ATP, DNA, Theories of anaesthetic action, cellular mechanisms",
author = "Lee, {S. T.} and Wu, {T. T.} and Yu, {P. Y.} and Chen, {R. M.}",
year = "2009",
month = "1",
doi = "10.1093/bja/aen322",
language = "English",
volume = "102",
pages = "80--89",
journal = "British Journal of Anaesthesia",
issn = "0007-0912",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway

AU - Lee, S. T.

AU - Wu, T. T.

AU - Yu, P. Y.

AU - Chen, R. M.

PY - 2009/1

Y1 - 2009/1

N2 - Background. Ketamine is widely used as an i.v. anaesthetic agent and as a drug of abuse. Hepatocytes contribute to the metabolism of endogenous and exogenous substances. This study evaluated the toxic effects of S-(+)-ketamine and possible mechanisms using human hepatoma HepG2 cells as the experimental model. Methods. HepG2 cells were exposed to S-(+)-ketamine. Cell viability and the release of lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (GPT) were measured to determine the toxicity of S-(+)-ketamine to HepG2 cells. Cell morphology, DNA fragmentation, and apoptotic cells were analysed to evaluate the mechanism of S-(+)-ketamine-induced cell death. Amounts of Bax, an apoptotic protein, and cytochrome c in the cytoplasm or mitochondria were quantified by immunoblotting. Cellular adenosine triphosphate levels were analysed using a bioluminescence assay. Caspases-3, -9, and -6 were measured fluorometrically. Results. Exposure of HepG2 cells to S-(+)-ketamine increased the release of LDH and GPT, but decreased cell viability (all P

AB - Background. Ketamine is widely used as an i.v. anaesthetic agent and as a drug of abuse. Hepatocytes contribute to the metabolism of endogenous and exogenous substances. This study evaluated the toxic effects of S-(+)-ketamine and possible mechanisms using human hepatoma HepG2 cells as the experimental model. Methods. HepG2 cells were exposed to S-(+)-ketamine. Cell viability and the release of lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (GPT) were measured to determine the toxicity of S-(+)-ketamine to HepG2 cells. Cell morphology, DNA fragmentation, and apoptotic cells were analysed to evaluate the mechanism of S-(+)-ketamine-induced cell death. Amounts of Bax, an apoptotic protein, and cytochrome c in the cytoplasm or mitochondria were quantified by immunoblotting. Cellular adenosine triphosphate levels were analysed using a bioluminescence assay. Caspases-3, -9, and -6 were measured fluorometrically. Results. Exposure of HepG2 cells to S-(+)-ketamine increased the release of LDH and GPT, but decreased cell viability (all P

KW - Anaesthetics i.v., ketamine

KW - Liver, hepatotoxicity

KW - Metabolism, ATP, DNA

KW - Theories of anaesthetic action, cellular mechanisms

UR - http://www.scopus.com/inward/record.url?scp=57349180886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57349180886&partnerID=8YFLogxK

U2 - 10.1093/bja/aen322

DO - 10.1093/bja/aen322

M3 - Article

C2 - 19001360

AN - SCOPUS:57349180886

VL - 102

SP - 80

EP - 89

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

IS - 1

ER -