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 B₄ (LTB₄) 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 LTB₄ content during ischemia (ID₅₀ = 0.645 mg/kg) with a slightly higher potency than that of AA-861 (ID₅₀ = 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 (ID₅₀ = 1.71 mg/kg and 4.28 mg/kg, respectively). These protective effects were more efficient than those of AA-861 (ID₅₀ = 1.86 mg/kg and no effect, respectively), LY255283 (ID₅₀ = 18.1 mg/kg and 11.5 mg/kg, respectively), and ONO-4057 (ID₅₀ = 8.38 mg/kg and 9.44 mg/kg, respectively), which are LTB₄ receptor antagonists. These results suggest that ardisiaquinone A may protect the liver against damage due to I/R in rats.

Key words

Ardisiaquinone A - Ardisia sieboldii - Myrsinaceae - leukotriene B₄ - ischemia-reperfusion - liver - rat

References

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