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Protective effect of the 5-lipoxygenase inhibitor ardisiaquinone A on hepatic ischemia-reperfusion injury in rats.

Abstract
The protective effects of the 5-lipoxygenase inhibitor ardisiaquinone A, a compound isolated from Ardisia sieboldii, on hepatic ischemia-reperfusion (I/R) injury was studied in rats. Hepatic I/R injury was induced by occlusion of the portal vein and the hepatic artery for 60 min, followed by reperfusion for 24 h. The content of leukotriene B (4) (LTB (4)) in the liver increased during ischemia. Serum alanine aminotransferase (ALT) levels, a marker of hepatic parenchymal cell injury, and hepatic myeloperoxidase (MPO) activity, a marker of neutrophil accumulation, significantly increased 6 - 9 h after reperfusion. Treatment with ardisiaquinone A (0.1 - 2 mg/kg, i. p.) 30 min prior to ischemia dose-dependently prevented the increase in LTB (4) content during ischemia (ID (50) = 0.645 mg/kg) with a slightly higher potency than that of AA-861 (ID (50) = 0.728 mg/kg), a known reference 5-lipoxygenase inhibitor. Ardisiaquinone A also attenuated the increase in MPO activity and serum ALT levels at 6 h after reperfusion (ID (50) = 1.71 mg/kg and 4.28 mg/kg, respectively). These protective effects were more efficient than those of AA-861 (ID (50) = 1.86 mg/kg and no effect, respectively), LY255283 (ID (50) = 18.1 mg/kg and 11.5 mg/kg, respectively), and ONO-4057 (ID (50) = 8.38 mg/kg and 9.44 mg/kg, respectively), which are LTB (4) receptor antagonists. These results suggest that ardisiaquinone A may protect the liver against damage due to I/R in rats.
AuthorsNobuaki Matsui, Nobuyuki Fukuishi, Yoshiyasu Fukuyama, Yumiko Yasui, Masaaki Akagi
JournalPlanta medica (Planta Med) Vol. 71 Issue 8 Pg. 717-20 (Aug 2005) ISSN: 0032-0943 [Print] Germany
PMID16142634 (Publication Type: Journal Article)
Chemical References
  • Benzoquinones
  • Enzyme Inhibitors
  • Lipoxygenase Inhibitors
  • Plant Extracts
  • Protective Agents
  • ardisiaquinone A
Topics
  • Animals
  • Ardisia
  • Benzoquinones (administration & dosage, pharmacology, therapeutic use)
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (administration & dosage, pharmacology, therapeutic use)
  • Lipoxygenase Inhibitors
  • Liver Diseases (enzymology, prevention & control)
  • Male
  • Phytotherapy
  • Plant Extracts (administration & dosage, pharmacology, therapeutic use)
  • Protective Agents (administration & dosage, pharmacology, therapeutic use)
  • Rats
  • Rats, Wistar
  • Reperfusion Injury (prevention & control)

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