ABSTRACT
The aim of this study was to evaluate the effect of insulin-like growth factor-I (IGF-I) on lethality and liver function in experimental acute liver failure. Intravenous co-administration of D-galactosamine (GalN) and lipopolysaccharide (LPS) to rats induced high mortality and marked increases in aspartate aminotransferase, alanine aminotransferase and total bilirubin, associated with hypoglycemia. One-hour pre-treatment with IGF-I significantly prevented lethality and blood parameter changes in rats. Histological examination also showed that massive hepatocellular hemorrhagic necrosis and inflammatory cell infiltration around peri-central veins in the liver, as well as shrinkage of cytoplasm and nuclear condensation, were induced by GalN plus LPS injection, but these all were improved by pre-treatment with IGF-I. Overall, this study showed that IGF-I treatment resulted in effective prevention of lethal acute liver failure in rats induced by GalN plus LPS, suggesting a therapeutic potential for IGF-I in the prevention of acute liver failure.
Subject(s)
Galactosamine/toxicity , Insulin-Like Growth Factor I/therapeutic use , Lipopolysaccharides/toxicity , Liver Failure, Acute/chemically induced , Liver Failure, Acute/pathology , Liver Failure, Acute/prevention & control , Liver/pathology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Bilirubin/blood , Disease Models, Animal , Galactosamine/administration & dosage , Humans , Injections, Intravenous , Lipopolysaccharides/administration & dosage , Liver/drug effects , Rats , Recombinant Proteins/therapeutic useABSTRACT
Inhibition of colonic propulsive motility is the main contributor to postoperative ileus in humans. Experimental models for investigating colonic propulsion in surgically induced postoperative ileus have not previously been available. This study was designed to assess whether adenosine A(1) receptor antagonists (R)-1-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-piperidin-2-yl acetic acid (FK352) and 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) reverse the colonic motility disorder in newly developed rat experimental ileus models. When rats underwent anesthesia (pentobarbital) or surgical traumas (partial gastrectomy, cecectomy or gentle touching of the colon with fingers), colonic propulsive motility was evaluated by migration of intracolonically injected dye in awake unrestrained rats. Propulsive motility resulted in significant decrease after the treatment of the anesthesia or partial gastrectomy. Intravenous administration of either adenosine A(1) receptor antagonist reversed the slowed colonic propulsion in these experimental ileus models. The present study suggests that the blockade of adenosine A(1) receptors has therapeutic potential for postoperative ileus.
