Thioacetamide-induced hepatic fibrosis in the common marmoset

Exp Anim. 2018 Jul 30;67(3):321-327. doi: 10.1538/expanim.17-0156. Epub 2018 Mar 22.

Abstract

The common marmoset (Callithrix jacchus) is a nonhuman primate that is used for preclinical research on stem cell transplantation therapies due to its similarity to human beings as well as its small size, enabling researchers to perform experiments without preparing a large number of cells. In this study, we developed a marmoset hepatic fibrosis model for regenerative medicine research. Six female marmosets aged 4-6 years were administered thioacetamide (TAA) at a dose of 2.5-40 mg/kg two or three times a week. Hepatic fibrosis was assessed by liver biopsy when blood chemistry indicated liver damage. Administration of TAA increased total bile acid, aspartate aminotransferase, and total bilirubin and decreased serum albumin levels. Following more than 11 weeks of continuous injection of TAA, histological analyses detected hepatic fibrosis in all animals. Type IV collagen 7S serum levels in animals with hepatic fibrosis were significantly higher than in normal animals as a possible marker of hepatic fibrosis in marmosets. Serial liver biopsies following the last administration of TAA revealed that induced fibrosis remained up to 11 weeks. The results suggest that continuous TAA administration induces persistent hepatic fibrosis in the common marmoset and this nonhuman primate hepatic fibrosis model have the possibility to evaluate the therapeutic effects of test samples to ameliorate hepatic fibrosis.

Keywords: liver fibrosis; marmoset; nonhuman primate; thioacetamide.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Callithrix*
  • Collagen Type IV / blood
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical
  • Female
  • Liver / pathology
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / pathology
  • Regenerative Medicine
  • Thioacetamide / administration & dosage
  • Thioacetamide / adverse effects*

Substances

  • Biomarkers
  • Collagen Type IV
  • Thioacetamide