Skip to main content

BRIEF RESEARCH REPORT article

Front. Gastroenterol.
Sec. Gastroenterology and Cancer
Volume 3 - 2024 | doi: 10.3389/fgstr.2024.1427820

A rat model of cirrhosis with well-differentiated hepatocellular carcinoma induced by thioacetamide

Provisionally accepted
Zhiping Hu Zhiping Hu 1*Takeshi Kurihara Takeshi Kurihara 1*Yiyue Sun Yiyue Sun 1*Zeliha Cetin Zeliha Cetin 1*Rodrigo M. Florentino Rodrigo M. Florentino 1Lanuza A P Faccioli Lanuza A P Faccioli 1Zhenghao Liu Zhenghao Liu 1*Bo Yang Bo Yang 1*Alina Ostrowska Alina Ostrowska 1,2*Alejandro Soto-Gutierrez Alejandro Soto-Gutierrez 1,2*Evan Delgado Evan Delgado 1,2*
  • 1 University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
  • 2 Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

The final, formatted version of the article will be published soon.

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis aggressive cholangiocarcinoma in addition to well-differentiated HCC, providing a model for early-stage, stage and a mixed liver cancer phenotype. This model is characterized by increased fibrosis, altered liver architecture, and increased hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats.This TAA-induced cirrhosis and mixed HCC rat model successfully replicates the clinical progression of human HCC, particularly in terms of liver function impairment and early-stage liver cancer characteristics. It serves as a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.

    Keywords: Thioacetamide, cholangiocarcinoma (CCA), Hepatocellular carcinoma, Fibrosis, cirrhosis, Mixed phenotype

    Received: 04 May 2024; Accepted: 17 Oct 2024.

    Copyright: © 2024 Hu, Kurihara, Sun, Cetin, Florentino, A P Faccioli, Liu, Yang, Ostrowska, Soto-Gutierrez and Delgado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhiping Hu, University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, United States
    Takeshi Kurihara, University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, United States
    Yiyue Sun, University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, United States
    Zeliha Cetin, University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, United States
    Zhenghao Liu, University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, United States
    Bo Yang, University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, United States
    Alina Ostrowska, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, 15261, Pennsylvania, United States
    Alejandro Soto-Gutierrez, University of Pittsburgh Medical Center, Pittsburgh, 15213, Pennsylvania, United States
    Evan Delgado, Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, 15261, Pennsylvania, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.