Pharmacological stimulation of Wnt/beta-catenin signaling pathway attenuates the course of thioacetamide-induced acute liver failure

Title:

Pharmacological stimulation of Wnt/beta-catenin signaling pathway attenuates the course of thioacetamide-induced acute liver failure

Creator:

Koblihová, Eva, Mrázová, Iveta, Vaňourková, Zdenka, Maxová, Hana, Kikerlová, Soňa, Husková, Zuzana, Ryska, Miroslav, Froněk, Jiří, and Vernerová, Zdenka

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:53c31f32-6403-4a4b-b6cc-db1c93eb644c
uuid:53c31f32-6403-4a4b-b6cc-db1c93eb644c
doi:10.33549/physiolres.934071

Subject:

acute liver failure, thioacetamide, and Wnt/β-catenin signaling pathway

Type:

model:article and TEXT

Format:

počítač and online zdroj

Description:

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.

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Coverage:

113-126

Source:

Physiological research | 2020 Volume:69 | Number:1

Harvested from:

CDK

Metadata only:

false