Kim MC van Mierlo, Simon AWG Dello, Mechteld C de Jong, Hans MH van Eijk, Theo M de Kok,
Jacob J Briedé, Frank G Schaap, Steven WM Olde Damink, Cornelius HC Dejong
van Mierlo et al., J Clin Transl Res, 2017; 3(S2): 6
Published online: March 25, 2018
Abstract
Background and Aim: Animal studies indicated that systemic ophthalmic acid (OPH) is a biomarker
for hepatic glutathione (GSH) homeostasis, an important determinant of liver function. We aimed to clarify
whether OPH levels can be used as a read-out for hepatic GSH homeostasis after paracetamol (APAP)
challenges during pylorus-preserving pancreaticoduodenectomy (PPPD) or partial hepatectomy (PH).
Methods: Nineteen patients undergoing PPPD (n=7, control group) or PH (n=12) were included. APAP
(1000 mg) was administered intravenously before resection (first challenge), and six and twelve hours later,
with sequential blood sampling during this period. Arterial, hepatic and portal venous blood samples and
liver biopsies were taken on three occasions during the first APAP challenge. Plasma and hepatic OPH and
GSH levels were quantified, and venous-arterial differences were calculated to study hepatic release.
Results: Systemic GSH levels decreased during the course of the APAP challenge in both surgical groups,
without notable change in OPH levels. Hepatic GSH and OPH content was not affected within ~3 hours
after administration of the first APAP dose in patients undergoing PPPD or PH. In this period, net release of
OPH by the liver was observed only in patients undergoing PPPD.
Conclusions: The drop in circulating GSH levels following APAP administrations, did not result in an
increase in plasma OPH in both patients with an intact liver and in those undergoing liver resection.
Hepatic content of GSH and OPH was not affected during the first APAP dose. It is uncertain whether
hepatic GSH homeostasis was sufficiently challenged in the present study (trial number: NL26884.068.09 /
09-3-010).
Relevance for patients: In the present study, plasma OPH seemed not useful as a marker for GSH
depletion because APAP administration during liver surgery did not lead to (immediate) GSH depletion or
increased OPH levels. Based on stable levels of hepatic GSH, OPH and thiyl radicals during surgery,
standard APAP administration seems to be safe in a postoperative care program with regards to GSH
homeostasis in this specific population. However, no general statements can be made on the basis of the
current experiment, since GSH homeostasis and susceptibility to xenobiotic toxicity are influenced by
several metabolic and genetic factors.
DOI: http://dx.doi.org/10.18053/jctres.03.2017S2.006
Author affiliation
1 Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands
2 Department of Surgery, Maastricht University, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands
3 Department of Toxicogenomics, Maastricht University Medical Center, Maastricht, the Netherlands
4 Maastricht University, GROW School for Oncology and Developmental Biology, Maastricht, the Netherlands
5 Department of General-, Visceral- and Transplant Surgery, Universitätsklinikum Aachen, Aachen, Germany
6 UCL Institute for Liver and Digestive Health, Division of Medicine, London, United Kingdom
*Corresponding author
Steven WM Olde Damink
Department of Surgery, Maastricht University, NUTRIM School of Nutrition and Translational Research in Metabolism, 6229 ER Maastricht, the Netherlands
Email: steven.oldedamink@maastrichtuniversity.nl
Handling editor
Michal Heger
Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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