Induction of hepatotoxicity by sanguinarine is associated with oxidation of protein thiols and disturbance of mitochondrial respiration

Cheuk-Sing Choy, Khoot Peng Cheah, Hung Yi Chiou, Joe Sharg Li, Yung Hung Liu, Seet Foong Yong, Wen Ta Chiu, Jiunn Wang Liao, Chien Ming Hu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Sanguinarine (SANG) has been suggested to be one of the principle constituents responsible for the toxicity of Argemone mexicana seed oil. In this study, we focused on the possible mechanism of SANG-induced hepatotoxicity. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, hepatic vacuolization, lipid accumulation and lipid peroxidation of the liver were increased, and triglyceride (TG) was decreased in SANG-treated mice (10 mg kg?1 i.p.), indicating damage to the liver. SANG induced cell death and DNA fragmentation, in a concentration- (0-30 μM) and time-dependent (0-24 h) manner, and the cytotoxicity of SANG (15 μM) was accompanied by an increase in reactive oxygen species and a lessening in protein thiol content; these outcomes were reversed by glutathione, N-acetyl-L-cysteine and 1,4-dithiothretol, and slightly improved by other antioxidants in hepatocytes. SANG can affect the function of mitochondria, leading to the depletion of the mitochondrial membrane potential and adenosine 5′-triphosphate content of hepatocytes. SANG caused an uncoupling effect of the respiratory chain at lower concentrations, but inhibited the respiratory chain at higher concentrations in mitochondria isolated from rat liver. In conclusion, the data suggest that SANG is a liver toxin that induces cytotoxicity in liver cells, possibly through oxidation of protein thiols, resulting in oxidative stress on the cells and disturbance of mitochondrial function.

Original languageEnglish
Pages (from-to)945-956
Number of pages12
JournalJournal of Applied Toxicology
Volume28
Issue number8
DOIs
Publication statusPublished - Nov 2008

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Sulfhydryl Compounds
Respiration
Oxidation
Liver
Proteins
Mitochondria
Cytotoxicity
Electron Transport
Hepatocytes
Argemone
Lipids
Oilseeds
Oxidative stress
sanguinarine
Mitochondrial Membrane Potential
Acetylcysteine
DNA Fragmentation
Cell death
Aspartate Aminotransferases
Alanine Transaminase

Keywords

  • Hepatotoxicity
  • Lipid peroxidation
  • Mitochondria
  • Oxygen consumption
  • Protein thiol
  • Reactive oxygen species
  • Sanguinarine

ASJC Scopus subject areas

  • Toxicology

Cite this

Induction of hepatotoxicity by sanguinarine is associated with oxidation of protein thiols and disturbance of mitochondrial respiration. / Choy, Cheuk-Sing; Cheah, Khoot Peng; Chiou, Hung Yi; Li, Joe Sharg; Liu, Yung Hung; Yong, Seet Foong; Chiu, Wen Ta; Liao, Jiunn Wang; Hu, Chien Ming.

In: Journal of Applied Toxicology, Vol. 28, No. 8, 11.2008, p. 945-956.

Research output: Contribution to journalArticle

Choy, Cheuk-Sing ; Cheah, Khoot Peng ; Chiou, Hung Yi ; Li, Joe Sharg ; Liu, Yung Hung ; Yong, Seet Foong ; Chiu, Wen Ta ; Liao, Jiunn Wang ; Hu, Chien Ming. / Induction of hepatotoxicity by sanguinarine is associated with oxidation of protein thiols and disturbance of mitochondrial respiration. In: Journal of Applied Toxicology. 2008 ; Vol. 28, No. 8. pp. 945-956.
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abstract = "Sanguinarine (SANG) has been suggested to be one of the principle constituents responsible for the toxicity of Argemone mexicana seed oil. In this study, we focused on the possible mechanism of SANG-induced hepatotoxicity. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, hepatic vacuolization, lipid accumulation and lipid peroxidation of the liver were increased, and triglyceride (TG) was decreased in SANG-treated mice (10 mg kg?1 i.p.), indicating damage to the liver. SANG induced cell death and DNA fragmentation, in a concentration- (0-30 μM) and time-dependent (0-24 h) manner, and the cytotoxicity of SANG (15 μM) was accompanied by an increase in reactive oxygen species and a lessening in protein thiol content; these outcomes were reversed by glutathione, N-acetyl-L-cysteine and 1,4-dithiothretol, and slightly improved by other antioxidants in hepatocytes. SANG can affect the function of mitochondria, leading to the depletion of the mitochondrial membrane potential and adenosine 5′-triphosphate content of hepatocytes. SANG caused an uncoupling effect of the respiratory chain at lower concentrations, but inhibited the respiratory chain at higher concentrations in mitochondria isolated from rat liver. In conclusion, the data suggest that SANG is a liver toxin that induces cytotoxicity in liver cells, possibly through oxidation of protein thiols, resulting in oxidative stress on the cells and disturbance of mitochondrial function.",
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AU - Li, Joe Sharg

AU - Liu, Yung Hung

AU - Yong, Seet Foong

AU - Chiu, Wen Ta

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AU - Hu, Chien Ming

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AB - Sanguinarine (SANG) has been suggested to be one of the principle constituents responsible for the toxicity of Argemone mexicana seed oil. In this study, we focused on the possible mechanism of SANG-induced hepatotoxicity. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, hepatic vacuolization, lipid accumulation and lipid peroxidation of the liver were increased, and triglyceride (TG) was decreased in SANG-treated mice (10 mg kg?1 i.p.), indicating damage to the liver. SANG induced cell death and DNA fragmentation, in a concentration- (0-30 μM) and time-dependent (0-24 h) manner, and the cytotoxicity of SANG (15 μM) was accompanied by an increase in reactive oxygen species and a lessening in protein thiol content; these outcomes were reversed by glutathione, N-acetyl-L-cysteine and 1,4-dithiothretol, and slightly improved by other antioxidants in hepatocytes. SANG can affect the function of mitochondria, leading to the depletion of the mitochondrial membrane potential and adenosine 5′-triphosphate content of hepatocytes. SANG caused an uncoupling effect of the respiratory chain at lower concentrations, but inhibited the respiratory chain at higher concentrations in mitochondria isolated from rat liver. In conclusion, the data suggest that SANG is a liver toxin that induces cytotoxicity in liver cells, possibly through oxidation of protein thiols, resulting in oxidative stress on the cells and disturbance of mitochondrial function.

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