Single dose of anti-transforming growth factor-beta1 monoclonal antibody enhances liver regeneration after partial hepatectomy in biliary-obstructed rats.
BACKGROUND
Transforming growth factor (TGF) beta is a potent inhibitor of hepatocyte DNA synthesis and liver regeneration. TGF-beta(1) expression progressively increases in obstructive jaundice. We investigated the effect of TGF-beta(1) blockage on liver regeneration in rats induced with obstructive jaundice.


METHODS
Male Wistar-albino rats were divided into three groups: sham, control, and study groups. In the study and control groups, the common bile duct was ligated and divided, and 7 days later a partial hepatectomy was performed. In the study group, anti-TGF-beta(1) monoclonal antibody (10-microg single dose) was administered immediately after the 70% hepatectomy. In the control group, those rats in which obstructive jaundice was induced received normal saline after the 70% hepatectomy, and nonjaundiced rats received anti-TGF-beta(1) monoclonal antibody after the 70% hepatectomy. Rats were sacrificed after 48 or 72 h. Relative liver weight, AST, ALT, total and conjugated bilirubin, and TGF-beta(1) levels were measured. The mitotic index and proliferating cell nuclear antigen (PCNA) labeling index were evaluated as histopathologic parameters.


RESULTS
At 72 h, the TGF-beta(1) level in the study group was similar to that in the sham group, whereas TGF-beta(1) in the study group was significantly lower than that of the jaundiced control group at 48 or 72 h (P < 0.001). The relative liver weight, mitotic index, and PCNA labeling index were significantly higher in the study group than in the jaundiced control group at 48 and 72 h (P < 0.001). The AST, ALT, and TGF-beta(1) levels were significantly higher in the jaundiced control group compared to the study group after 48 and 72 h, whereas these values were significantly lower in the nonjaundiced control group (P < 0.001).


CONCLUSIONS
In obstructive jaundiced rats, TGF-beta(1) blockage with anti-TGF-beta(1) monoclonal antibody after liver resection improved liver regeneration both morphologically and functionally.
Deneme
Mehmet Ali
MA
Department of Surgery, Erciyes University School of Medicine, Kayseri, Turkey.
Ok
Engin
E
Akcan
Alper
A
Akyildiz
Hizir
H
Soyuer
Isin
I
Muhtaroglu
Sebahattin
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D006498:Hepatectomy / Q000379:methods*; D022781:Hepatocytes / Q000166:cytology; D007155:Immunologic Factors / Q000494:pharmacology*; D041781:Jaundice, Obstructive / Q000188:drug therapy* / Q000276:immunology; D008115:Liver Regeneration / Q000276:immunology*; D008297:Male; D008938:Mitosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D018809:Proliferating Cell Nuclear Antigen; D053773:Transforming Growth Factor beta1; D004247:DNA; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin