Evidence map›Paper›PMID 26681794›Full record

ReviewPhysiological reviews2016

Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications.

Xin Gen Lei, Jian-Hong Zhu, Wen-Hsing Cheng, Yongping Bao, Ye-Shih Ho, Amit R Reddi, Arne Holmgren, Elias S J Arnér

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Physiological reviews, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed, 3 pooled it
11.9field-weighted citation impact, top 1% 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

187 citing papers in PubMed, 3 syntheses or guidelines pooled it, 417 citations in OpenAlex.

  1. Pooled it
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  14. Biocatalytic Nanoregulators Restore Joint Redox-Immune Homeostasis in Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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127 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

8 authors at 6 institutions in 3 countries.

Xin Gen LeiBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Jian-Hong ZhuBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Wen-Hsing ChengBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Yongping BaoBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Ye-Shih HoBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Amit R ReddiBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Arne HolmgrenBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Elias S J ArnérBeijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing,China; Department of Animal Science, Cornell University, Ithaca, New York; Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Mississippi State, Mississippi; Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan; Georgia Institute of Technology, School of Chemistry and Biochemistry, Parker Petit Institute for Bioengineering and Biosciences, Atlanta, Georgia; and Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Georgia Institute of Technology · USKarolinska Institutet · SEChina Agricultural University · CNCornell University · USWayne State University · USWenzhou Medical University · CN

Funding

ANTIOXIDATIVE ROLE OF GPX1 IN VIVO OF TRANSGENIC MICER01DK053018 · NIDDK · CORNELL UNIVERSITY ITHACA · PI LEI, XINGEN · 1997 to 2013
$2.8M
Imaging heme based mitochondrial-cell signaling networks in cell and animal models of heavy metal toxicityR21ES025661 · NIEHS · GEORGIA INSTITUTE OF TECHNOLOGY · PI REDDI, AMIT RAM · 2015 to 2016
$416k
Redox regulation in the hepatostatR21AG055022 · NIA · MONTANA STATE UNIVERSITY - BOZEMAN · PI ARNER, ELIAS S.J., NAGY, PETER · 2016 to 2017
$382k
NIA NIH HHS R21 AG055022NIDDK NIH HHS DK 53018NIDDK NIH HHS R01 DK053018NIEHS NIH HHS R21 ES025661NIEHS NIH HHS R21ES025661
6 · The paper itself

Abstract

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from aerobic metabolism, as a result of accidental electron leakage as well as regulated enzymatic processes. Because ROS/RNS can induce oxidative injury and act in redox signaling, enzymes metabolizing them will inherently promote either health or disease, depending on the physiological context. It is thus misleading to consider conventionally called antioxidant enzymes to be largely, if not exclusively, health protective. Because such a notion is nonetheless common, we herein attempt to rationalize why this simplistic view should be avoided. First we give an updated summary of physiological phenotypes triggered in mouse models of overexpression or knockout of major antioxidant enzymes. Subsequently, we focus on a series of striking cases that demonstrate "paradoxical" outcomes, i.e., increased fitness upon deletion of antioxidant enzymes or disease triggered by their overexpression. We elaborate mechanisms by which these phenotypes are mediated via chemical, biological, and metabolic interactions of the antioxidant enzymes with their substrates, downstream events, and cellular context. Furthermore, we propose that novel treatments of antioxidant enzyme-related human diseases may be enabled by deliberate targeting of dual roles of the pertaining enzymes. We also discuss the potential of "antioxidant" nutrients and phytochemicals, via regulating the expression or function of antioxidant enzymes, in preventing, treating, or aggravating chronic diseases. We conclude that "paradoxical" roles of antioxidant enzymes in physiology, health, and disease derive from sophisticated molecular mechanisms of redox biology and metabolic homeostasis. Simply viewing antioxidant enzymes as always being beneficial is not only conceptually misleading but also clinically hazardous if such notions underpin medical treatment protocols based on modulation of redox pathways.

Indexed as

Health StatusOxidative StressAnimalsAntioxidantsDisease Models, AnimalEnzyme InductionEnzyme RepressionEnzymesGene Knockdown TechniquesGenetic Predisposition to DiseaseHumansMice, TransgenicNutritional StatusOxidation-ReductionPhenotypeReactive Nitrogen SpeciesAntioxidantsEnzymesReactive Nitrogen SpeciesReactive Oxygen Species

Identifiers

PMID26681794
PMCPMC4839492
OpenAlexW2246949337

What OpenQuestion holds

Textmetadata
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.