TY - JOUR
T1 - Transforming growth factor-α (TGF-α) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats
AU - Kokudo, Norihiro
AU - Kothary, Piyush C.
AU - Eckhauser, Frederic E.
AU - Raper, Steven E.
N1 - Funding Information:
Normal liver has a remarkable capacity to regenerate and allows safe performance of partial hepatectomy in patients with liver tumors [l, 21. Morphology and function of the liver return to normal once the regenerative process is completed. In liver cirrhosis, liver regeneration is impaired. Cirrhotic patients are at an increased risk of postoperative liver failure and related morbidity and mortality. This problem is not uncommon as 70 to 80% of hepatocellular carcinomas arise in cirrhotic liver [3]. Although there have been a number of efforts to reduce the volume of cirrhotic liver to be resected with- 1 This work was supported by NIH Grant 1 R29 DK42485 (S.E.R.). ’ The authors gratefully acknowledge the technical assistance of Akiyo Shigematsu, Ph.D., and Akiko Hatori, MS., Institute of Whole Body Metabolism, Chiba, Japan.
PY - 1992/6
Y1 - 1992/6
N2 - Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-α (TGF-α), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 ± 3.4 cpm/μg DNA (means ± SEM), which was significantly lower than in normal rats (37.3 ± 3.4 cpm/μg DNA, P < 0.05). Exogenous TGF-α (30 nmole/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 ± 8.2 cpm/μg DNA, P < 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-α had no effect on normal regenerating liver (42.5 ± 8.8 cpm/μg DNA, NS). Although the significance of TGF-α-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.
AB - Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-α (TGF-α), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 ± 3.4 cpm/μg DNA (means ± SEM), which was significantly lower than in normal rats (37.3 ± 3.4 cpm/μg DNA, P < 0.05). Exogenous TGF-α (30 nmole/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 ± 8.2 cpm/μg DNA, P < 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-α had no effect on normal regenerating liver (42.5 ± 8.8 cpm/μg DNA, NS). Although the significance of TGF-α-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.
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U2 - 10.1016/0022-4804(92)90144-O
DO - 10.1016/0022-4804(92)90144-O
M3 - Article
C2 - 1528043
AN - SCOPUS:0026713101
VL - 52
SP - 648
EP - 655
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 6
ER -