Acute liver failure (ALF) is known for extremely high mortality
rate, the result of widespread damage of hepatocytes. Orthotopic
liver transplantation is the only effective therapy but its
application is limited by the scarcity of donor organs. Given the
importance in the liver biology of Wnt/β-catenin signaling
pathway, we hypothesized that its stimulation could enhance
hepatocyte regeneration and attenuate the course of
thioacetamide (TAA)-induced ALF in Lewis rats. Chronic
treatment with Wnt agonist was started either immediately after
hepatotoxic insult (“early treatment”) or when signs of ALF had
developed (“late treatment”). Only 23 % of untreated Lewis rats
survived till the end of experiment. They showed marked
increases in plasma alanine aminotransferase (ALT) activity and
bilirubin and ammonia (NH3) levels; plasma albumin decreased
significantly. “Early” and “late” Wnt agonist treatment raised the
final survival rate to 69 % and 63 %, respectively, and
normalized ALT, NH3, bilirubin and albumin levels. In conclusion,
the results show that treatment with Wnt agonist attenuates the
course of TAA-induced ALF in Lewis rats, both with treatment
initiated immediately after hepatotoxic insult and in the phase
when ALF has already developed. Thus, the pharmacological
stimulation of Wnt/β-catenin signaling pathway can present
a new approach to ALF treatment.