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) production inhibitor E3330, [(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinolyl)]-2-nonyl-2-+ ++propenoic acid] on liver regeneration in rats subjected to 70% partial hepatectomy. The BrdU labeling index was 53.5 +/- 3.8% 24 h after partial hepatectomy alone and was significantly inhibited by E3330 (25 and 50 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 levels in liver tissue were 187 +/- 18, 123 +/- 47, and 89 +/- 33 pg/mg total protein, respectively, with a significant decrease by E3330 administration (p < 0.01). TNF-alpha mRNA expression in liver tissue was also reduced by E3330. These results suggest that TNF-alpha promotes liver regeneration after partial hepatectomy.
Kimura
T
T
First Department of Internal Medicine, Yamaguchi University, School of Medicine, Japan.
Sakaida
I
I
Terai
S
S
Matsumura
Y
Y
Uchida
K
K
Okita
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006498:Hepatectomy; D008115:Liver Regeneration; D008297:Male; D011422:Propionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
D016227:Benzoquinones; D011422:Propionates; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C075569:E 3330; D000410:Alanine Transaminase