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
FITC-linked Fibrin-Binding Peptide and real-time live confocal microscopy as a novel tool to visualize fibrin(ogen) in coagulation
Background and Aim: Although fibrinogen has been established as a key player in the process of coagulation, many questions about the role of fibrinogen under specific conditions remain. Confocal microscopic assessment of...
The first steps in the evaluation of a "black-box" decision support tool: a protocol and feasibility study for the evaluation of Watson for Oncology
Background and aim: Medical specialists aim to provide evidence-based care based on the most recent scientific insights, but with the ongoing expansion of medical literature it seems unfeasible to remain updated. ”Black-...
Keeping track of all ongoing colorectal cancer trials using a mobile application: Usability and satisfaction results of the Dutch Colorectal Cancer Group Trials application
Background and Aim: Both the number and complexity of medical trials are increasing vastly. To facilitate easy access to concise trial information, a freely available mobile application including all ongoing clinical tri...
CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis
Background: Idiopathic pulmonary fibrosis is a devastating fibrotic diffuse parenchymal lung disorder that remains refractory to pharmacological therapies. Therefore, novel treatments are urgently required. CCAAT/enhance...
Biomarkers for glioblastoma multiforme: status quo
Background: Glioblastoma (GBM) is the most frequent and most malignant central nervous system (CNS) tumor. GBM shows poor prognosis with a median overall survival of 14.6 months, despite current surgical and adjuvant the...