Ophthalmic acid as a read-out for hepatic glutathione metabolism in humans
Journal Title: Journal of Clinical and Translational Research - Year 2018, Vol 3, Issue 2
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. 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.
Authors and Affiliations
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
Keywords
Related Articles
- EP ID EP678762
- DOI -
- Views 190
- Downloads 0
Administration of DDAVP did not improve the pharmacokinetics of FVIII concentrate in a clinically significant manner
Background: The half-life and mean residence time (MRT) of infused recombinant factor VIII (FVIII) concentrate are associated with pre-infusion levels of von Willebrand factor (VWF) in severely affected hemophilia A pati...
Layer-by-layer heparinization of decellularized liver matrices to reduce thrombogenicity of tissue engineered grafts
Background: Tissue–engineered liver grafts may offer a viable alternative to orthotopic liver transplantation and help overcome the donor organ shortage. Decellularized liver matrices (DLM) have a preserved vasculature a...
Making 'null effects' informative: statistical techniques and inferential frameworks
Being able to interpret ‘null effects’ is important for cumulative knowledge generation in science. To draw informative conclusions from null-effects, researchers need to move beyond the incorrect interpretation of a non...
Diagnostic validity of the anxiety and depression questions from the Well-Being Process Questionnaire
Background: Previous research shows that the Well-being Process Questionnaire (WPQ) has good content validity, construct validity, discriminant validity and reliability. Aims: The present research examined the diagnosti...
Obesity and diabetes accelerate hepatocarcinogenesis via hepatocyte proliferation independent of NF-κB or Akt/mTORC1
Background: There are strong links between obesity, diabetes and hepatocellular carcinoma (HCC), but molecular mechanisms remain unclear. Aim: We tested the proposed involvement of NF-κB, IL-6/STAT3 and Akt/mTORC1 befor...