Liver fibrosis model

Authors:

Philip M E. Probert

Mohammad R. Ebrahimkhani

Fiona Oakley

Jelena Mann

Alastair D. Burt

Derek A. Mann

Matthew C. Wright

Publication:

Toxicology Research 3, 98-109 doi: 10.1039/C3TX50069A

Publish Date:

28 August 2013

Background

Bile duct ligation (BDL), a common model for hepatic periportal fibrosis, is a surgical procedure involving the double ligation of the common bile duct. This procedure presents several challenges, as it is an irreversible, severe procedure, in which the severity of the induced injury cannot be modulated, resulting in high mortality of animals.

Summary

Methapyrilene was used as a sedative and anti-histamine until the late 70s when it was found to promote liver damage in rats. In this paper, chronic administration of methapyrilene is proposed as an alternative model to bile duct ligation. This refined model does not require surgery and is less severe as it allows for modulating the degree of injury, is reversible, and results in minimal mortality.

Key Actions

Always review the literature to identify refined protocols, models, or non-animal alternatives.
Seek to avoid using BDL and use more refined models wherever possible.

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Further questions

MP administration is less severe because it:
- Allows the degree of injury to be adjusted by altering the dose of MP
- Results in reduced mortality
- It is reversible; the injury, inflammation, fibrosis, and ductular reaction all reverse within three weeks of treatment withdrawal, making it a more sensitive model for identifying effective anti-fibrogenic drugs
Partial BDL (pBDL), where only a portion of the bile duct is ligated, significantly improves animal welfare and survival rates compared to conventional BDL. Chemical models, such as those using carbon tetrachloride (CCl4) or thioacetamide (TAA), and various dietary models, also offer alternatives to the surgical invasiveness of full BDL. While these models still induce significant fibrosis, they generally avoid the immediate high mortality associated with complete BDL.

Authors

Philip M. E. Probert - Newcastle University

Mohammad R. Ebrahimkhani - New York University School of Medicine

Fiona Oakley - Newcastle University

Jelena Mann - Newcastle University

Alastair D. Burt - Newcastle University

Derek A. Mann - Newcastle University

Matthew C. Wright - Newcastle University