INHIBITION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION RETARDS LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY IN RATS

We studied the effects of a tumor necrosis factor-alpha (TNF-alpha) pr oduction inhibitor E3330, y-6-methyl-1,4-benzoquinolyl)]-2-nonyl-2-pro penoic acid] on liver regeneration in rats subjected to 70% partial he patectomy, The BrdU labeling index was 53.5 +/- 3.8% 24 h after partia l hepatectomy alone and was significantly inhibited by E3330 (25 and 5 0 mg/kg) in a dose-dependent manner (43.3 +/- 2.1% and 19.0 +/- 10.3%, respectively; p<0.05, p<0.01). In these 3 groups, TNF-alpha protein l evels in liver tissue were 187 +/- 18, 123 +/- 47, and 89 +/- 33 pg/mg total protein, respectively, with a significant decrease by E3330 adm inistration (p<0.01), TNF-alpha mRNA expression in liver tissue was al so reduced by E3330, These results suggest that TNF-alpha promotes liv er regeneration after partial hepatectomy. (C) 1997 Academic Press.