Growth hormone prevents acute liver injury induced by cardiopulmonary bypass in a rat model

Abstract

Cardiopulmonary bypass-induced acute liver injury is a life-threatening complication thought to be associated with the inflammatory response and the acute-phase response. Recombinant human growth hormone can modulate the acute-phase response and inflammatory response. We tested the protective effect of growth hormone on cardiopulmonary bypass-induced liver injury in the rat. Adult male Sprague-Dawley rats (group G received 2.5 mg/kg recombinant human growth hormone intramuscularly at 8 am every 24 hours for 3 days and just before the initiation of cardiopulmonary bypass; group C served as a control group) underwent cardiopulmonary bypass (120 minutes, 120 mL x kg(-1) x min(-1), 34 degrees C) and were killed 3 hours after the termination of cardiopulmonary bypass. Administration of recombinant human growth hormone markedly increased serum insulin-like growth factor and insulin-like growth factor-binding protein 3 levels compared with those seen in group C. Group G showed significantly lower serum concentrations of alanine aminotransferase and total bilirubin after cardiopulmonary bypass termination. Those receiving recombinant human growth hormone demonstrated a significant increase in serum prealbumin and transferrin levels and a marked decrease in serum amyloid A and C-reactive protein levels. Recombinant human growth hormone significantly decreased serum tumor necrosis factor alpha and interleukin 1beta levels, whereas no changes were found for serum interleukin 6 and interleukin 10 levels. Recombinant human growth hormone significantly increased total liver protein content and hepatocyte proliferation and decreased hepatocyte apoptosis versus values seen in group C. These results suggest that growth hormone prevents cardiopulmonary bypass-induced acute liver injury in a rat model through decreases in acute-phase proteins, proinflammatory cytokines tumor necrosis factor alpha and interleukin 1beta, and hepatocyte apoptosis, which is associated with increases in constitutive hepatic proteins, total liver protein content, and hepatocyte proliferation. This strategy of pretreatment with growth hormone might be a prospective management for preventing acute liver injury when major cardiac surgery with cardiopulmonary bypass is performed.