Evidence map›Paper›PMID 26905452›Full record

ArticleJournal of chromatography. B, Analytical technologies in the biomedical and life sciences2016

Pitfalls in the analysis of the physiological antioxidant glutathione (GSH) and its disulfide (GSSG) in biological samples: An elephant in the room.

Daniela Giustarini, Dimitrios Tsikas, Graziano Colombo, Aldo Milzani, Isabella Dalle-Donne, Paolo Fanti, Ranieri Rossi

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
10.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.

  1. Pooled it
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  16. NADSkeletal muscle · 2025
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  18. Nanomedicine-Driven Modulation of Reductive Stress for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 3 countries.

Daniela GiustariniDepartment of Life Sciences, Laboratory of Pharmacology and Toxicology, University of Siena, Via A. Moro 4, 53100 Siena, Italy.
Dimitrios TsikasCentre of Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Graziano ColomboDepartment of Biosciences, University of Milan, Via Celoria 26, I-2033 Milan, Italy.
Aldo MilzaniDepartment of Biosciences, University of Milan, Via Celoria 26, I-2033 Milan, Italy.
Isabella Dalle-DonneDepartment of Biosciences, University of Milan, Via Celoria 26, I-2033 Milan, Italy.
Paolo FantiDivision of Nephrology, Department of Medicine, The University of Texas Health Science Center San Antonio, and Audie L. Murphy VA Hospital, San Antonio, TX 78229, USA.
Ranieri RossiDepartment of Life Sciences, Laboratory of Pharmacology and Toxicology, University of Siena, Via A. Moro 4, 53100 Siena, Italy. Electronic address: ranieri@unisi.it.
University of Milan · ITUniversity of Siena · ITAudie L. Murphy Memorial VA Hospital · USMedizinische Hochschule Hannover · DE

Funding

N-Acetylcysteine and Milk Thistle for Treatment of Diabetic NephropathyR21AT004490 · NCCIH · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FANTI, PAOLO · 2009 to 2011
$499k
Correction of glutathione deficiency for treatment of diabetic nephropathyI01CX000264 · VA · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · PI FANTI, PAOLO · 2011 to 2014
–
CSRD VA I01 CX000264NCCIH NIH HHS AT004490NCCIH NIH HHS R21 AT004490
6 · The paper itself

Abstract

Glutathione (GSH) is the most abundant low-molecular-mass thiol within cells and one of the major antioxidant compounds in body fluids. Under pro-oxidant conditions, two GSH molecules donate one electron each and are converted into glutathione disulfide (GSSG). The GSH/GSSG molar ratio is considered a powerful index of oxidative stress and disease risk. Despite high interest in GSH/GSSG titration as measures of thiol redox balance, no broad agreement has yet been reached as to the best pre-analytical and analytical methods for the quantitation of these molecules in biological samples. Consequently, measured concentrations of GSH and GSSG and calculated GSH/GSSG molar ratios vary widely among laboratories. Here, we describe in detail the main analytical and pre-analytical problems related to the artificial oxidation of the sulfhydryl (SH) group of GSH that occur during sample manipulation. We underline how this aspect has been neglected for long time after its first description more than fifty years ago. Finally, selected reliable procedures and methods to measure GSH and GSSG in biological samples are discussed.

Indexed as

AnimalsAntioxidantsChemistry Techniques, AnalyticalGlutathioneGlutathione DisulfideHumansOxidation-ReductionAntioxidantsGlutathioneGlutathione DisulfideGlutathioneGlutathione disulfideOxidative stressProtocols

Identifiers

PMID26905452
PMCPMC4829456
OpenAlexW2274096479

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.