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 i s still unknown. LTB(4) stagnates in the liver with obstructive jaundi ce, because LTB(4) is ex excreted in the bile; therefore, LTB(4) may h ave an effect on liver regeneration after hepatectomy with obstructive jaundice. Release of obstructive jaundice and simultaneous 70% hepate ctomy was performed in rats to study the effect of B-lipoxygenase inhi bitor (AA-861) on liver regeneration. Group 1 underwent hepatectomy wi th administration of 0.1 mt dimethyl sulfoxide (DMSO), group 2 underwe nt 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 mt DMSO, group 4 underwent release o f obstructive jaundice and hepatectomy with administration of 0.1 mL D MSO, and group 5 underwent relief of obstructive jaundice and hepatect omy with administration of AA-861 (20 mg/kg/d). DMSO or AA-861 was adm inistered 24 hours before, during, and 24 hours after hepatectomy in e ach group. Whole blood LTB(4) and serum alanine aminotransferase (ALT) , total bilirubin, and bromodeoxyuridine labeling index (LI) were meas ured before and after hepatectomy. The LTB(4) level increased during o bstructive jaundice and after hepatectomy, LTB(4) and serum ALT levels were significantly lower after hepatectomy in the rats that were admi nistered AA-861, and a significantly higher LI was observed at 24 hour s after hepatectomy in rats receiving AA-861. Inhibition of 5-lipoxyge nase promotes Liver regeneration and decreases hepatocyte injury after hepatectomy associated with obstructive jaundice.