PhD Scientific Days 2025

Pathological and Oncological Sciences II.

Is regenerated rat liver more vulnerable to thioacetamide-induced fibrosis?

Name of the presenter

Váncza Lóránd

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research

Authors

Lóránd Váncza¹, Kristóf-Gergő Nagy², Manuela Juhász¹, Katalin Dezső¹

1: Department of Pathology and Experimental Cancer Research
2: George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureş

Text of the abstract

Background:
The liver has an exceptional regenerative capacity. Following partial hepatectomy in rats the liver regains its original mass within a few days through hepatocyte proliferation. However, no data is available on the vulnerability of the regenerated liver to hepatotoxins. Thioacetamide (TAA) is a widely used hepatotoxic agent for studying liver fibrosis in animal experiments.
Objective:
Our research aimed to compare the effect of thioacetamide in control and regenerated rat livers, and to compare the per oral (PO) and intraperitoneal (IP) routes of administration.
Materials and Methods:
Liver regeneration was induced in F344 rats by traditional 70% partial hepatectomy. Two months after surgery, regenerated (R) and age-matched control (C) animals received either PO TAA (600 mg/L in drinking water for 3 months) or IP TAA (200 mg/kg in saline, three times weekly for 1 month). Liver samples were formalin-fixed, paraffin-embedded, and stained with picrosirius red staining, then scanned. Fibrotic areas were evaluated using ImageJ software.
Results:
Following PO administration of TAA, the proportion of fibrotic areas was significantly higher in regenerated livers (C: 6.15% vs. R: 7.86%). In contrast, IP TAA treatment resulted in significantly lower ratio of fibrotic areas in regenerated livers (C: 5.21% vs. R: 2.47%).
Conclusions:
Our results highlight two key findings: (i) Control and regenerated livers behave differently in TAA-induced fibrosis models, regardless of the route of administration. (ii) The two routes of TAA administration led to opposite results.
We hypothesize that due to the reduced metabolic capacity of regenerated hepatocytes, high levels of free TAA accumulate following IP administration.
Elevated levels of TAA inhibit the formation of the active metabolite (TAA-S-S-dioxide) and thus the development of fibrosis in these livers. We plan to verify this hypothesis using low-dose IP TAA treatment (50 mg/kg).
Funding:
FK138673 OTKA, Semmelweis 250+ Kiválósági PhD Ösztöndíj 123799/DIDIT/2024