Treatment of cirrhotic rats with epidermal growth factor and insulin accelerates liver DNA synthesis after partial hepatectomy

Masaji Hashimoto, Piyush C. Kothary, Frederic E. Eckhauser, Steven E. Raper

Research output: Contribution to journalArticlepeer-review

Abstract

Prevention of postoperative hepatic failure is important after hepatic resection. In patients with cirrhosis, impaired liver function and regenerative capacity after major hepatic resection are associated with increased morbidity and mortality. In this study, a combination of epidermal growth factor (EGF) and insulin were used as hepatotrophic factors in an attempt to stimulate DNA synthesis after 70% hepatectomy (HTX). Regenerative capacity was evaluated in normal and cirrhotic rat liver by measuring DNA synthesis in vivo. Micronodular liver cirrhosis was established by the simultaneous oral administration of CCl4 and phenobarbital. Epidermal growth factor plus insulin was injected subcutaneously immediately after and 12 h after HTX or sham operation was performed. Rats were killed 24 h after the operation and liver regeneration was estimated by [3H]-thymidine incorporation into DNA as well as an autoradiographic nuclear labelling index. Hepatectomy increased [3H]-thymidine incorporation significantly in both normal and cirrhotic rats. In cirrhotic rats, [3H]-thymidine incorporation after HTX was significantly lower than in normal rats and administration of a combination of EGF and insulin after HTX enhanced [3H]- thymidine incorporation. In conclusion, DNA synthesis 24 h after HTX is decreased in cirrhotic rats compared with normal rats and EGF supplementation with insulin accelerates DNA synthesis in hepatectomized cirrhotic rats. The data suggest that administration of combinations of exogenous hepatotrophic factors may play a useful role in the treatment of cirrhotic patients undergoing major hepatic resection.

Original languageEnglish (US)
Pages (from-to)1259-1265
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume13
Issue number12
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Epidermal growth factor
  • Experimental liver cirrhosis
  • Insulin
  • Liver regeneration

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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