Protective effect of the 5-lipoxygenase inhibitor ardisiaquinone A on hepatic ischemia-reperfusion injury in rats.
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.
Matsui
Nobuaki
N
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima City, Japan. matsui@ph.bunri-u.ac.jp
Fukuishi
Nobuyuki
N
Fukuyama
Yoshiyasu
Y
Yasui
Yumiko
Y
Akagi
Masaaki
M
D000818:Animals; D031644:Ardisia; D016227:Benzoquinones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors; D008107:Liver Diseases / Q000201:enzymology / Q000517:prevention & control; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D020011:Protective Agents; C091304:ardisiaquinone A