Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice

Hepatology. 1990 Jun;11(6):916-22. doi: 10.1002/hep.1840110603.


A hypothesis has been proposed by this laboratory that endogenous gut-derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy. Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration. To test this hypothesis liver regeneration was assessed in germ-free euthymic mice that lack the gram-negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin. To complement the germ-free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide-resistant C3H/HeJ mice were also examined. Liver regeneration, quantified by [3H] thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ-free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide-resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals. Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection. Germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration. Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice as compared with conventional euthymic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • DNA / biosynthesis
  • DNA Replication
  • Drug Resistance
  • Endotoxins / pharmacology
  • Germ-Free Life
  • Glucagon / blood
  • Hepatectomy / methods*
  • Insulin / blood
  • Lipopolysaccharides / pharmacology*
  • Liver / metabolism
  • Liver / physiology
  • Liver Regeneration*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Nude
  • Portal Vein
  • Salmonella enteritidis


  • Endotoxins
  • Insulin
  • Lipopolysaccharides
  • DNA
  • Glucagon