Abstract
In clinical ischemia/reperfusion injury, damage resulting from oxidative and nitrosative stress is generally considered crucial for graft functioning. Yet, there is increasing evidence that modern clinical transplantation including orthotopic liver transplantation (OLT) is not associated with elevation of oxidative and nitrosative stress upon organ reoxygenation. We measured two currently used biomarkers of oxidative stress, i.e., 15(S)-8-iso-prostaglandin F2a (15(S)-8-iso-PGF2a) and cis-epoxyoctadecanoic acid (cis-EpOA), in human plasma during the entire time duration of OLT in eight patients suffering from end-stage liver disease. No considerable concentration changes of 15(S)-8-iso-PGF2a and cis-EpOA were observed, indicating lack of oxidative stress. Previously, we found in the same patients that nitrosative stress, measured as 3-nitrotyrosine and 3-nitrotyrosinoalbumin. Yet, as 15(S)-8-iso-PGF2a, cis-EpOA and 3-nitrotyrosine are produced both by chemical and enzymatic reactions, the current concepts of oxidative and nitrosative stress require reconsideration.
Highlights
Assessment of oxidative and nitrosative stress is based on the measurement of their respective so-called biomarkers
Oxidative stress was found to be involved in numerous diseases as well as in clinical ischemia/reperfusion injury including orthotopic liver transplantation (OLT)
By measuring the “established” biomarkers of oxidative stress (i.e., 15(S)-8-iso-PGF2α), and nitrosative stress (i.e., 3-nitrotyrosine and 3-nitrotyrsoine albumin) using reliable gas chromatography-tandem mass spectrometry-based analytical approaches, we found that oxidative stress and nitrosative stress are elevated in patients with end-stage liver disease, but they do not change during OLT
Summary
Assessment of oxidative and nitrosative stress is based on the measurement of their respective so-called biomarkers. In humans suffering from end-stage liver disease, we measured plasma concentrations of cis-EpOA and found it to be lower than that in healthy subjects [8]. This finding may suggest diminished hepatic synthesis of cis-EpOA by CYP isoform and/or lacking elevated oxidative stress in liver disease. In plasma samples of the same patients, we found elevated 15(S)-8-iso-PGF2α, 3-nitrotyrosine, and 3-nitrotyrosinoalbumin concentrations [2, 3], suggesting elevated oxidative and nitrosative stress in end-stage liver disease. Because of the duality of oxidative stress and for many other reasons, notably including analytical shortcomings and pitfalls [1], the conventional concept of oxidative stress in human disease has been questioned [1, 11]
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