Gut-derived endotoxin elicits hepatotrophic factor secretion for liver regeneration

Abstract

The influence of exogenous endotoxin pretreatment on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats with midline laparotomy and liver manipulation as the sham control. Animals were pretreated with endotoxin at a dose of 33 micrograms/100 g sc or iv 24 h before surgery and then fasted. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA, and plasma levels of hepatotrophic factors were measured by radioimmunoassay or radioreceptor assay. Systemic endotoxemia occurred after exogenous endotoxin administration as well as after partial hepatectomy due to absorption of exogenous endotoxin from the gut into the portal circulation as determined by quantitative chromogenic lysate assay of perchloric acid-extracted plasma samples. Alterations in putative hepatotrophic factors, including insulin, glucagon, epidermal growth factor, vasopressin, and triiodothyronine, were remarkable similar in response to endotoxemia by exogenous endotoxin administration and by endogenous endotoxin absorption from the gut after partial hepatectomy. Our hypothesis purports that gut-derived systemic endotoxemia elicits hepatotrophic factor secretion for liver regeneration after partial hepatectomy and that endotoxin pretreatment expedites the hepatotrophic factor response, thus accelerating DNA synthesis in the proliferating liver after 67% resection.