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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F20%3A43919423" target="_blank" >RIV/00216208:11120/20:43919423 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61383082:_____/20:00000679 RIV/00216208:11130/20:10402513 RIV/00023001:_____/20:00079433

Výsledek na webu

<a href="https://doi.org/10.33549/physiolres.934071" target="_blank" >https://doi.org/10.33549/physiolres.934071</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33549/physiolres.934071" target="_blank" >10.33549/physiolres.934071</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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/beta-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 (&quot;early treatment&quot;) or when signs of ALF had developed (&quot;late treatment&quot;). 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. &quot;Early&quot; and &quot;late&quot; 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/beta-catenin signaling pathway can present a new approach to ALF treatment.

Název v anglickém jazyce

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

Popis výsledku anglicky

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/beta-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 (&quot;early treatment&quot;) or when signs of ALF had developed (&quot;late treatment&quot;). 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. &quot;Early&quot; and &quot;late&quot; 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/beta-catenin signaling pathway can present a new approach to ALF treatment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological Research

ISSN

0862-8408

e-ISSN

—

Svazek periodika

69

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

14

Strana od-do

113-126

Kód UT WoS článku

000514830600009

EID výsledku v databázi Scopus

2-s2.0-85081101012