Abstract

In the present study, we investigated the effects and mechanisms of a novel potent antioxidant, octyl caffeate, on the induction of iNOS expression by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in cultured primary rat aortic smooth muscle cells (RASMCs) in vitro and LPS-induced hypotension in vivo. Octyl caffeate (0.1-1.0μM) exerted a concentration-dependent inhibition of iron-catalyzed lipid peroxidation in rat brain homogenates. Furthermore, octyl caffeate (20, 50, and 100μM) concentration-dependently diminished the initial rate of superoxide-induced NBT reduction and the enzymatic activity of xanthine oxidase. It also concentration-dependently (1-50μM) inhibited the NO production, iNOS protein and messenger RNA expressions upon stimulation by LPS (100μg/mL)/IFN-γ (100U/mL) in RASMCs. In addition, we found that octyl caffeate did not significantly affect IκBα degradation stimulated by LPS/IFN-γ in RASMCs. On the other hand, octyl caffeate (10 and 50μM) significantly suppressed activation of c-Jun-N-terminal kinase and extracellular signal-regulated kinase. Moreover, octyl caffeate (10mg/kg, i.v.) significantly inhibited the fall in mean arterial pressure stimulated by LPS (7.5mg/kg) in rats. In conclusion, we demonstrate that a novel potent antioxidant, octyl caffeate, significantly ameliorates circulatory failure of endotoxemia in vivo by a mechanism involving suppression of iNOS expression through inactivation of mitogen-activated protein kinases in RASMCs.

Original languageEnglish
Pages (from-to)1383-1392
Number of pages10
JournalBiochemical Pharmacology
Volume65
Issue number8
DOIs
Publication statusPublished - Apr 15 2003

Fingerprint

Nitric Oxide Synthase Type II
Gene expression
Interferons
Smooth Muscle Myocytes
Lipopolysaccharides
Muscle
Rats
Antioxidants
Cells
Gene Expression
Controlled Hypotension
Endotoxemia
JNK Mitogen-Activated Protein Kinases
Xanthine Oxidase
Extracellular Signal-Regulated MAP Kinases
octyl caffeate
Mitogen-Activated Protein Kinases
Superoxides
Lipid Peroxidation
Shock

Keywords

  • Antioxidant
  • Endotoxic shock
  • iNOS
  • LPS/IFN-γ
  • MAPK
  • Octyl caffeate

ASJC Scopus subject areas

  • Pharmacology

Cite this

A novel antioxidant, octyl caffeate, suppression of LPS/IFN-γ-induced inducible nitric oxide synthase gene expression in rat aortic smooth muscle cells. / Hsiao, George; Shen, Ming Yi; Chang, Wen Chiung; Cheng, Yu Wen; Pan, Shiow Lin; Kuo, Yueh Hsiung; Chen, Tzeng Fu; Sheu, Joen Rong.

In: Biochemical Pharmacology, Vol. 65, No. 8, 15.04.2003, p. 1383-1392.

Research output: Contribution to journalArticle

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abstract = "In the present study, we investigated the effects and mechanisms of a novel potent antioxidant, octyl caffeate, on the induction of iNOS expression by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in cultured primary rat aortic smooth muscle cells (RASMCs) in vitro and LPS-induced hypotension in vivo. Octyl caffeate (0.1-1.0μM) exerted a concentration-dependent inhibition of iron-catalyzed lipid peroxidation in rat brain homogenates. Furthermore, octyl caffeate (20, 50, and 100μM) concentration-dependently diminished the initial rate of superoxide-induced NBT reduction and the enzymatic activity of xanthine oxidase. It also concentration-dependently (1-50μM) inhibited the NO production, iNOS protein and messenger RNA expressions upon stimulation by LPS (100μg/mL)/IFN-γ (100U/mL) in RASMCs. In addition, we found that octyl caffeate did not significantly affect IκBα degradation stimulated by LPS/IFN-γ in RASMCs. On the other hand, octyl caffeate (10 and 50μM) significantly suppressed activation of c-Jun-N-terminal kinase and extracellular signal-regulated kinase. Moreover, octyl caffeate (10mg/kg, i.v.) significantly inhibited the fall in mean arterial pressure stimulated by LPS (7.5mg/kg) in rats. In conclusion, we demonstrate that a novel potent antioxidant, octyl caffeate, significantly ameliorates circulatory failure of endotoxemia in vivo by a mechanism involving suppression of iNOS expression through inactivation of mitogen-activated protein kinases in RASMCs.",
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T1 - A novel antioxidant, octyl caffeate, suppression of LPS/IFN-γ-induced inducible nitric oxide synthase gene expression in rat aortic smooth muscle cells

AU - Hsiao, George

AU - Shen, Ming Yi

AU - Chang, Wen Chiung

AU - Cheng, Yu Wen

AU - Pan, Shiow Lin

AU - Kuo, Yueh Hsiung

AU - Chen, Tzeng Fu

AU - Sheu, Joen Rong

PY - 2003/4/15

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N2 - In the present study, we investigated the effects and mechanisms of a novel potent antioxidant, octyl caffeate, on the induction of iNOS expression by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in cultured primary rat aortic smooth muscle cells (RASMCs) in vitro and LPS-induced hypotension in vivo. Octyl caffeate (0.1-1.0μM) exerted a concentration-dependent inhibition of iron-catalyzed lipid peroxidation in rat brain homogenates. Furthermore, octyl caffeate (20, 50, and 100μM) concentration-dependently diminished the initial rate of superoxide-induced NBT reduction and the enzymatic activity of xanthine oxidase. It also concentration-dependently (1-50μM) inhibited the NO production, iNOS protein and messenger RNA expressions upon stimulation by LPS (100μg/mL)/IFN-γ (100U/mL) in RASMCs. In addition, we found that octyl caffeate did not significantly affect IκBα degradation stimulated by LPS/IFN-γ in RASMCs. On the other hand, octyl caffeate (10 and 50μM) significantly suppressed activation of c-Jun-N-terminal kinase and extracellular signal-regulated kinase. Moreover, octyl caffeate (10mg/kg, i.v.) significantly inhibited the fall in mean arterial pressure stimulated by LPS (7.5mg/kg) in rats. In conclusion, we demonstrate that a novel potent antioxidant, octyl caffeate, significantly ameliorates circulatory failure of endotoxemia in vivo by a mechanism involving suppression of iNOS expression through inactivation of mitogen-activated protein kinases in RASMCs.

AB - In the present study, we investigated the effects and mechanisms of a novel potent antioxidant, octyl caffeate, on the induction of iNOS expression by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) in cultured primary rat aortic smooth muscle cells (RASMCs) in vitro and LPS-induced hypotension in vivo. Octyl caffeate (0.1-1.0μM) exerted a concentration-dependent inhibition of iron-catalyzed lipid peroxidation in rat brain homogenates. Furthermore, octyl caffeate (20, 50, and 100μM) concentration-dependently diminished the initial rate of superoxide-induced NBT reduction and the enzymatic activity of xanthine oxidase. It also concentration-dependently (1-50μM) inhibited the NO production, iNOS protein and messenger RNA expressions upon stimulation by LPS (100μg/mL)/IFN-γ (100U/mL) in RASMCs. In addition, we found that octyl caffeate did not significantly affect IκBα degradation stimulated by LPS/IFN-γ in RASMCs. On the other hand, octyl caffeate (10 and 50μM) significantly suppressed activation of c-Jun-N-terminal kinase and extracellular signal-regulated kinase. Moreover, octyl caffeate (10mg/kg, i.v.) significantly inhibited the fall in mean arterial pressure stimulated by LPS (7.5mg/kg) in rats. In conclusion, we demonstrate that a novel potent antioxidant, octyl caffeate, significantly ameliorates circulatory failure of endotoxemia in vivo by a mechanism involving suppression of iNOS expression through inactivation of mitogen-activated protein kinases in RASMCs.

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