Inhibition of 5-lipoxygenase promotes the regeneration of the liver after partial hepatectomy in normal and icteric rats.
The role of leukotriene (LT) on liver regeneration after hepatectomy is still unknown. LTB4 stagnates in the liver with obstructive jaundice, because LTB4 is excreted in the bile; therefore, LTB4 may have an effect on liver regeneration after hepatectomy with obstructive jaundice. Release of obstructive jaundice and simultaneous 70% hepatectomy was performed in rats to study the effect of 5-lipoxygenase inhibitor (AA-861) on liver regeneration. Group 1 underwent hepatectomy with administration of 0.1 mL dimethyl sulfoxide (DMSO), group 2 underwent hepatectomy with administration of AA-861 (20 mg/kg/d) dissolved in 0.1 mL DMSO, group 3 underwent hepatectomy with administration of AA-861 (40 mg/kg/d) dissolved in 0.1 mL DMSO, group 4 underwent release of obstructive jaundice and hepatectomy with administration of 0.1 mL DMSO, and group 5 underwent relief of obstructive jaundice and hepatectomy with administration of AA-861 (20 mg/kg/d). DMSO or AA-861 was administered 24 hours before, during, and 24 hours after hepatectomy in each group. Whole blood LTB4 and serum alanine aminotransferase (ALT), total bilirubin, and bromodeoxyuridine labeling index (LI) were measured before and after hepatectomy. The LTB4 level increased during obstructive jaundice and after hepatectomy. LTB4 and serum ALT levels were significantly lower after hepatectomy in the rats that were administered AA-861, and a significantly higher LI was observed at 24 hours after hepatectomy in rats receiving AA-861. Inhibition of 5-lipoxygenase promotes liver regeneration and decreases hepatocyte injury after hepatectomy associated with obstructive jaundice.
Urade
M
M
Department of Surgery II, School of Medicine, Kanazawa University, Japan.
Izumi
R
R
Kitagawa
H
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D001663:Bilirubin / Q000097:blood; D001973:Bromodeoxyuridine; D002779:Cholestasis / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D006498:Hepatectomy / Q000379:methods; D007975:Leukotriene B4 / Q000097:blood; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D000410:Alanine Transaminase; D001973:Bromodeoxyuridine; D001663:Bilirubin