Myocardial oxidative stress and toxicity induced by acute ethanol exposure in mice

Muralidhar Kannan, Lipeng Wang, Yujian Kang

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Alcoholic cardiomyopathy has been known for a long time, but there is little mechanistic insight into this important clinical problem. The present study was undertaken using a mouse model to test the hypothesis that alcohol exposure induces cardiac injury through induction of oxidative stress. Adult female Friend Virius B-type (FVB) mice were treated with ethanol by gavage at a dose of 5 g/kg. Six hours after the treatment, ethanol-induced myocardial injury was observed, as indicated by a significant increase in serum creatine phosphokinase activity, a common biomarker of myocardial injury, and myocardial ultrastructural alterations, predominantly mitochondrial swelling and cristae disarray and reduction in numbers. The myocardial injury was associated with a significant increase in the myocardial lipid peroxidation, determined by measuring thiobarbituric acid reactive substances (TBARS), and a significant increase in protein oxidation as measured by a protein carbonyl content assay. Acute alcohol exposure decreased glutathione (GSH) content in the heart, more so in the mitochondria than in the cytosol. These alcohol-induced myocardial injuries and oxidative stresses were all significantly inhibited by supplementation with N-acetyl-L-cysteine (NAC) prior to alcohol exposure. However, NAC did not affect the rise in blood alcohol concentrations following alcohol exposure. This study thus demonstrates that acute alcohol administration causes myocardial injury through, at least in part, the induction of oxidative stress. A rapid decrease in mitochondrial GSH content may be partially responsible for the observed mitochondrial damage.

Original languageEnglish (US)
Pages (from-to)553-559
Number of pages7
JournalExperimental Biology and Medicine
Volume229
Issue number6
DOIs
StatePublished - Jan 1 2004

Fingerprint

Oxidative stress
Toxicity
Oxidative Stress
Ethanol
Alcohols
Wounds and Injuries
Acetylcysteine
Alcoholic Cardiomyopathy
Mitochondrial Swelling
Thiobarbituric Acid Reactive Substances
Creatine Kinase
Mitochondria
Cytosol
Biomarkers
Lipid Peroxidation
Glutathione
Proteins
Swelling
Assays
Blood

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Myocardial oxidative stress and toxicity induced by acute ethanol exposure in mice. / Kannan, Muralidhar; Wang, Lipeng; Kang, Yujian.

In: Experimental Biology and Medicine, Vol. 229, No. 6, 01.01.2004, p. 553-559.

Research output: Contribution to journalArticle

@article{c69b1dbc848c41d598765079e505e094,
title = "Myocardial oxidative stress and toxicity induced by acute ethanol exposure in mice",
abstract = "Alcoholic cardiomyopathy has been known for a long time, but there is little mechanistic insight into this important clinical problem. The present study was undertaken using a mouse model to test the hypothesis that alcohol exposure induces cardiac injury through induction of oxidative stress. Adult female Friend Virius B-type (FVB) mice were treated with ethanol by gavage at a dose of 5 g/kg. Six hours after the treatment, ethanol-induced myocardial injury was observed, as indicated by a significant increase in serum creatine phosphokinase activity, a common biomarker of myocardial injury, and myocardial ultrastructural alterations, predominantly mitochondrial swelling and cristae disarray and reduction in numbers. The myocardial injury was associated with a significant increase in the myocardial lipid peroxidation, determined by measuring thiobarbituric acid reactive substances (TBARS), and a significant increase in protein oxidation as measured by a protein carbonyl content assay. Acute alcohol exposure decreased glutathione (GSH) content in the heart, more so in the mitochondria than in the cytosol. These alcohol-induced myocardial injuries and oxidative stresses were all significantly inhibited by supplementation with N-acetyl-L-cysteine (NAC) prior to alcohol exposure. However, NAC did not affect the rise in blood alcohol concentrations following alcohol exposure. This study thus demonstrates that acute alcohol administration causes myocardial injury through, at least in part, the induction of oxidative stress. A rapid decrease in mitochondrial GSH content may be partially responsible for the observed mitochondrial damage.",
author = "Muralidhar Kannan and Lipeng Wang and Yujian Kang",
year = "2004",
month = "1",
day = "1",
doi = "10.1177/153537020422900614",
language = "English (US)",
volume = "229",
pages = "553--559",
journal = "Experimental Biology and Medicine",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "6",

}

TY - JOUR

T1 - Myocardial oxidative stress and toxicity induced by acute ethanol exposure in mice

AU - Kannan, Muralidhar

AU - Wang, Lipeng

AU - Kang, Yujian

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Alcoholic cardiomyopathy has been known for a long time, but there is little mechanistic insight into this important clinical problem. The present study was undertaken using a mouse model to test the hypothesis that alcohol exposure induces cardiac injury through induction of oxidative stress. Adult female Friend Virius B-type (FVB) mice were treated with ethanol by gavage at a dose of 5 g/kg. Six hours after the treatment, ethanol-induced myocardial injury was observed, as indicated by a significant increase in serum creatine phosphokinase activity, a common biomarker of myocardial injury, and myocardial ultrastructural alterations, predominantly mitochondrial swelling and cristae disarray and reduction in numbers. The myocardial injury was associated with a significant increase in the myocardial lipid peroxidation, determined by measuring thiobarbituric acid reactive substances (TBARS), and a significant increase in protein oxidation as measured by a protein carbonyl content assay. Acute alcohol exposure decreased glutathione (GSH) content in the heart, more so in the mitochondria than in the cytosol. These alcohol-induced myocardial injuries and oxidative stresses were all significantly inhibited by supplementation with N-acetyl-L-cysteine (NAC) prior to alcohol exposure. However, NAC did not affect the rise in blood alcohol concentrations following alcohol exposure. This study thus demonstrates that acute alcohol administration causes myocardial injury through, at least in part, the induction of oxidative stress. A rapid decrease in mitochondrial GSH content may be partially responsible for the observed mitochondrial damage.

AB - Alcoholic cardiomyopathy has been known for a long time, but there is little mechanistic insight into this important clinical problem. The present study was undertaken using a mouse model to test the hypothesis that alcohol exposure induces cardiac injury through induction of oxidative stress. Adult female Friend Virius B-type (FVB) mice were treated with ethanol by gavage at a dose of 5 g/kg. Six hours after the treatment, ethanol-induced myocardial injury was observed, as indicated by a significant increase in serum creatine phosphokinase activity, a common biomarker of myocardial injury, and myocardial ultrastructural alterations, predominantly mitochondrial swelling and cristae disarray and reduction in numbers. The myocardial injury was associated with a significant increase in the myocardial lipid peroxidation, determined by measuring thiobarbituric acid reactive substances (TBARS), and a significant increase in protein oxidation as measured by a protein carbonyl content assay. Acute alcohol exposure decreased glutathione (GSH) content in the heart, more so in the mitochondria than in the cytosol. These alcohol-induced myocardial injuries and oxidative stresses were all significantly inhibited by supplementation with N-acetyl-L-cysteine (NAC) prior to alcohol exposure. However, NAC did not affect the rise in blood alcohol concentrations following alcohol exposure. This study thus demonstrates that acute alcohol administration causes myocardial injury through, at least in part, the induction of oxidative stress. A rapid decrease in mitochondrial GSH content may be partially responsible for the observed mitochondrial damage.

UR - http://www.scopus.com/inward/record.url?scp=2942626026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942626026&partnerID=8YFLogxK

U2 - 10.1177/153537020422900614

DO - 10.1177/153537020422900614

M3 - Article

C2 - 15169975

AN - SCOPUS:2942626026

VL - 229

SP - 553

EP - 559

JO - Experimental Biology and Medicine

JF - Experimental Biology and Medicine

SN - 1535-3702

IS - 6

ER -