The preventative role of growth hormone on acute liver injury induced by cardiopulmonary bypass in a rat model

Eur J Cardiothorac Surg. 2007 Jun;31(6):1037-43. doi: 10.1016/j.ejcts.2007.01.077.

Abstract

Objective: Cardiopulmonary bypass (CPB)-induced acute liver injury is a life-threatening complication after cardiac surgery and is thought to be associated with inflammatory response and acute-phase response (APR). Recombinant human growth hormone (rhGH) can modulate the APR and inflammatory response. Here, we tested the protective effect of GH on CPB-induced liver injury in the rat.

Methods: Adult male Sprague-Dawley rats (group G, received 2.5 mg/kg of rhGH intramuscularly at 8a.m. every 24h for 3 days and just before the initiation of CPB; group C served as control) underwent CPB (120 min, 120 ml/kg per minute, 34 degrees C) and were killed 3h after the termination of CPB.

Results: Administration of rhGH markedly increased serum insulin-like growth factor (IGF)-I and IGF-I-binding protein (IGFBP)-3 compared with group C. Group G showed significantly lower serum concentrations of alanine aminotransferase and total bilirubin after CPB termination. Those receiving rhGH demonstrated a significant increase in serum prealbumin and serum transferrin and a marked decrease in serum amyloid A and serum C-reactive protein compared with group C. rhGH significantly decreased serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), whereas no changes were found for serum IL-6 and IL-10 compared with group C. rhGH significantly increased total liver protein content, hepatocyte proliferation, and decreased hepatocyte apoptosis versus group C.

Conclusions: These results suggest that GH administration in rats seems to play a preventative role in acute liver injury associated with CPB via the decrease in acute-phase proteins, proinflammatory cytokines TNF-alpha and IL-1beta, and hepatocyte apoptosis, which is associated with increase in constitutive hepatic proteins, total liver protein content, and hepatocyte proliferation.

MeSH terms

  • Acute Disease
  • Acute-Phase Proteins / analysis
  • Acute-Phase Reaction / immunology
  • Animals
  • Apoptosis / immunology
  • Cardiopulmonary Bypass / adverse effects*
  • Carrier Proteins / blood
  • Cell Division / immunology
  • Cytokines / blood
  • Disease Models, Animal
  • Human Growth Hormone / administration & dosage*
  • Human Growth Hormone / blood
  • Immunohistochemistry / methods
  • Injections, Intramuscular
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / analysis
  • Liver / immunology
  • Liver / pathology
  • Liver / physiopathology
  • Liver Diseases / etiology
  • Liver Diseases / immunology
  • Liver Diseases / prevention & control*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / blood

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • Cytokines
  • Insulin-Like Growth Factor Binding Protein 3
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • somatotropin-binding protein