Biochemical Parameters for Longitudinal Monitoring of Liver Function in Rat Models of Partial Hepatectomy Following Liver Injury

PLoS One. 2013 Jun 18;8(6):e66383. doi: 10.1371/journal.pone.0066383. Print 2013.

Abstract

Background: While evaluation of liver function in preclinical animal studies is commonly performed at selected time-points by invasive determination of the liver/body weight ratio and histological analyses, the validation of longitudinal measurement tools for monitoring liver function are of major interest.

Aims: To longitudinally evaluate serum cholinesterase (CHE) and total serum bilirubin (TSB) levels as non-invasive markers to determine injury- and partial hepatectomy (PHx)-induced alterations of liver function in rats.

Methods: Male and female Lewis rats were subjected to either methionine/choline deficient (MCD) diet or treatment with FOLFOX chemotherapy prior to PHx. Body weight and CHE/TSB levels are determined weekly. Following PHx and at the study end, histological analyses of liver tissue are performed.

Results: Following MCD diet, but not after FOLFOX chemotherapy treatment, results indicate gender-specific alterations in serum CHE levels and gender-independent alterations in TSB levels. Likewise, histological analyses of resected liver parts indicate significant liver injury following MCD-diet, but not following FOLFOX treatment. While TSB levels rapidly recover following MCD diet/FOLFOX treatment combined with a PHx, serum CHE levels are subject to significant model- and gender-specific differences, despite full histopathological recovery of liver tissue.

Conclusions: Longitudinal measurements of serum CHE levels and TSB levels in rats are highly complementary as non-invasive parameters for evaluation of liver injury and/or recovery.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Body Weight
  • Diet
  • Female
  • Hepatectomy*
  • Liver / injuries*
  • Liver / metabolism
  • Liver / physiopathology
  • Liver Function Tests*
  • Male
  • Organ Size
  • Rats
  • Rats, Inbred Lew

Grants and funding

This work was supported by a BOF-NOI 2009 research grant from the University of Antwerp (granted to DY and KDG). NB holds a PhD-studentship from the Flemish Institute for Science and Technology (IWT-Vlaanderen). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.