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 177
- Downloads 0
Intravenous infusion of magnesium sulfate is not associated with cardiovascular, liver, kidney, and metabolic toxicity in adults
Background: Magnesium (Mg) deficiency contributes to the pathophysiology of numerous diseases. The therapeutic use of Mg has steadily increased over time. The increased in-hospital use of intravenous (IV) magnesium sulfa...
The effect of acute pain on executive function
Background and Aim: Executive functions are high-level cognitive processes that allow a person to successfully engage in an independent and self-fulfilling life. Previous literature indicates that chronic pain can affect...
Legal challenges for the implementation of advanced clinical digital decision support systems in Europe
Systems based on artificial intelligence and machine learning that facilitate decision making in health care are promising new tools in the era of ‘personalized’ or ‘precision’ medicine. As the volume of patient data and...
Inclusion of special populations in clinical research: important considerations and guidelines
Background: Trials that involve human participants call for experiments or observations that are performed in a clinical research setting. Currently, there are over 16,000 clinical trials open in the United States. Despi...
Laser-assisted vascular welding: op miza on of acute and post-hydra on welding strength
Background: Liquid solder laser-assisted vascular welding using biocompatible polymeric scaffolds (ssLAVW) is a novel technique for vascular anastomoses. Although ssLAVW has pronounced advantages over conventional suturi...