Reflections of an aging free radical
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In this mini-reflection, I explain how during my doctoral work in a Botany Department I first became interested in H 2 O 2 and later in my career in other reactive oxygen species, especially the role of "catalytic" iron and haem compounds (including leghaemoglobin) in promoting oxidative damage. The important roles that H 2 O 2, other ROS and dietary plants play in respect to humans are discussed. I also review the roles of diet-derived antioxidants in relation to human disease, presenting reasons why clinical trials using high doses of natural antioxidants have generally given disappointing results. Iron chelators and ergothioneine are reviewed as potential cytoprotective agents with antioxidant properties that may be useful therapeutically. The discovery of ferroptosis may also lead to novel agents that can be used to treat certain diseases.
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Apart from vitamin E, other antioxidants such as carotenoids, ascorbic acid, and flavonoids have been shown to have a very mild effect on preventing oxidative damage.
“With respect to antioxidant interventions, apart from vitamin E, other antioxidants such as carotenoids, ascorbic acid, and flavonoids have been shown to have a very mild effect on preventing oxidative damage (Halliwell 2020; Forman and Zhang 2021; Mangione et al. 2022).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Halliwell 2020
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Establishing Biomarkers of Oxidative Stress: The Measurement of Hydrogen Peroxide in Human Urine
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Self-citationAgeing in nematodes: do antioxidants extend lifespan in Caenorhabditis elegans?
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Self-citationPharmacological Regulation of Oxidative Stress in Stem Cells
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Self-citationMechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation
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Oxidative decarboxylation of glycollate and glyoxylate by leaf peroxisomes
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Self-citationGopaul, N. K., Halliwell, B. B., & Änggård, E. (2000) · Free Radical Research · doi:10.1080/10715760000300671 · Cited by 83 · see citing works
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Oxidative Damage in Ischemic Stroke Revealed Using Multiple Biomarkers
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Self-citationCharles, S. A., & Halliwell, B. B. (1981) · Planta · doi:10.1007/bf00395175 · Cited by 73 · see citing works
Self-citationOxidation of formate by peroxisomes and mitochondria from spinach leaves
Halliwell, B. B. (1974) · Biochemical Journal · doi:10.1042/bj1380077 · Cited by 72 · see citing works
Self-citationCoffee drinking increases levels of urinary hydrogen peroxide detected in healthy human volunteers
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Self-citationExcretion of Hydrogen Peroxide in Human Urine
Varma, S. D., & Devamanoharan, P. S. (1990) · Free Radical Research Communications · doi:10.3109/10715769009087976 · Cited by 68 · see citing works
Hydrogen peroxide in urine as a potential biomarker of whole body oxidative stress
Yuen, J. W. M., & Benzie, I. F. F. (2003) · Free Radical Research · doi:10.1080/10715760310001616032 · Cited by 67 · see citing works
Superoxide dismutase: a contaminant of bovine catalase (Short Communication)
Halliwell, B. B. (1973) · Biochemical Journal · doi:10.1042/bj1350379 · Cited by 66 · see citing works
Self-citationSubstrate Selectivity Check of the Ergothioneine Transporter
Tschirka, J., Kreisor, M., Betz, J., & Gründemann, D. (2018) · Drug Metabolism and Disposition · doi:10.1124/dmd.118.080440 · Cited by 66 · see citing works
Could Ergothioneine Aid in the Treatment of Coronavirus Patients?
Cheah, I. K.-M., & Halliwell, B. B. (2020) · Antioxidants · doi:10.3390/antiox9070595 · Cited by 66 · see citing works
Self-citationRole of antioxidants and a nutrient rich diet in Alzheimer's disease
Veurink, G., Perry, G. L., & Singh, S. K. (2020) · Open Biology · doi:10.1098/rsob.200084 · Cited by 65 · see citing works
Studies on ergothioncine. VI. Distribution and fluctuations of ergothioneine in rats.
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Self-citationIsoprostanes and phytoprostanes: Bioactive lipids
Durand, T., Bultel‐Poncé, V., Guy, A., Fangour, S. E., Rossi, J., & Galano, J. (2010) · Biochimie · doi:10.1016/j.biochi.2010.05.014 · Cited by 57 · see citing works
Aceto, G. M., Catalano, T., & Curia, M. C. (2020) · BioMed Research International · doi:10.1155/2020/1726309 · Cited by 57 · see citing works
Lee, J. C., Isaac, H. B., Wang, H., Huang, S. H., Long, L. H., Jenner, A. M., Kelly, R. P., & Halliwell, B. B. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.03.217 · Cited by 50 · see citing works
Self-citationIncreased Urinary Hydrogen Peroxide Levels Caused by Coffee Drinking.
Hiramoto, K., Kida, T., & Kikugawa, K. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.1467 · Cited by 49 · see citing works
Inhibition of amyloid‐induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model
Cheah, I. K.-M., Ng, L. T., Ng, L. F., Lam, V. Y. M., Gruber, J., Huang, C. Y. W., Goh, F., Lim, K. H. C., & Halliwell, B. B. (2019) · FEBS Letters · doi:10.1002/1873-3468.13497 · Cited by 49 · see citing works
Self-citationJackson, M. J., Stretton, C., & McArdle, A. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101484 · Cited by 48 · see citing works
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Antioxidant supplementation, redox deficiencies and exercise performance: A falsification design
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Kelly, R. P., Yeo, K. P., Isaac, H. B., Lee, J. C., Huang, S. H., Teng, L., Halliwell, B. B., & Wise, S. D. (2008) · Free Radical Research · doi:10.1080/10715760802087431 · Cited by 42 · see citing works
Self-citationGreen odor attenuates a cold pressor test-induced cardiovascular response in healthy adults
Oka, T., Hayashida, S., Kaneda, Y., Takenaga, M., Tamagawa, Y., Tsuji, S., & Hatanaka, A. (2008) · BioPsychoSocial Medicine · doi:10.1186/1751-0759-2-2 · Cited by 42 · see citing works
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NOX-free inflammasome activation
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Specificity of the ergothioneine transporter natively expressed in HeLa cells
Tucker, R. A. J., Cheah, I. K., & Halliwell, B. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.02.122 · Cited by 38 · see citing works
Self-citationMetabolomics of human fasting: new insights about old questions
Kondoh, H., Teruya, T., & Yanagida, M. (2020) · Open Biology · doi:10.1098/rsob.200176 · Cited by 37 · see citing works
Zhao, X., Kruzel, M. L., Ting, S., Sun, G., Savitz, S. I., & Aronowski, J. A. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20925667 · Cited by 36 · see citing works
Guo, C., Han, X., Guo, T., Zhang, W., Xuan, W.-Q., Ren, Y.-T., Wang, D., Chen, Y.-H., Meng, Y., Gao, H., et al. (2020) · Food & Function · doi:10.1039/d0fo00910e · Cited by 33 · see citing works
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DNA adduct profiling of in vitro colonic meat digests to map red vs. white meat genotoxicity
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Villamor, E., Moreno, L., Mohammed, R. A., Pérez‐Vizcaíno, F., & Cogolludo, A. L. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.04.008 · Cited by 27 · see citing works
Elevated F2-isoprostanes in thalassemic patients
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Self-citationEvans, P., Evans, R. W., Bomford, A. B., Williams, R. L., & Halliwell, B. B. (1994) · Free Radical Research · doi:10.3109/10715769409147511 · Cited by 24 · see citing works
Self-citationLee, J. C., Isaac, H. B., Huang, S. H., Long, L. H., Wang, H., Gruber, J., Ong, C. N., Kelly, R. P., & Halliwell, B. B. (2009) · Free Radical Research · doi:10.1080/10715760902942816 · Cited by 24 · see citing works
Self-citationFigueroa, D., & Young, F. M. (2020) · Antioxidants · doi:10.3390/antiox9010051 · Cited by 23 · see citing works
Sato, Y., Ogino, K., Sakano, N., Wang, D. H., Yoshida, J., AKAZAWA, Y., Kanbara, S., Inoue, K., Kubo, M., & Takahashi, H. (2012) · Free Radical Research · doi:10.3109/10715762.2012.759218 · Cited by 22 · see citing works
ON THE ORIGIN OF ANIMAL ERGOTHIONEINE
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Puppo, A., & Halliwell, B. B. (1989) · Free Radical Research Communications · doi:10.3109/10715768909074711 · Cited by 20 · see citing works
Self-citationReduction of ferrylmyoglobin in rat diaphragm
Eddy, L. J., Arduini, A., & Hochstein, P. E. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.259.6.c995 · Cited by 19 · see citing works
Halliwell, B. B. (2018) · Free Radical Research · doi:10.1080/10715762.2018.1512749 · Cited by 19 · see citing works
Self-citationNierenberg, J. L., He, J., Li, C., Gu, X., Shi, M., Razavi, A. C., Mi, X., Li, S., Bazzano, L., Anderson, A. H., et al. (2020) · Aging · doi:10.18632/aging.103362 · Cited by 19 · see citing works
Regulation of T Cell Function by Reactive Nitrogen and Oxygen Species in Collagen-Induced Arthritis
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Forbes, J. (2000) · Nutrition Research Reviews · doi:10.1079/095442200108728972 · Cited by 13 · see citing works
Halliwell, B. B., & Butt, V. S. (1972) · Biochemical Journal · doi:10.1042/bj1291157 · Cited by 13 · see citing works
Self-citationTeo, E., Batchu, K., Barardo, D., Xiao, L., Cazenave-Gassiot, A., Tolwinski, N., Wenk, M., Halliwell, B., & Gruber, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-27330-3 · Cited by 13 · see citing works
Self-citationTherapeutic applications of chelating drugs in iron metabolic disorders of the brain and retina
Shahandeh, A., Bui, B. V., Finkelstein, D. I., & Nguyen, C. T. O. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24685 · Cited by 13 · see citing works
Determination of ergothioneine in red blood cells by high-performance liquid chromatography
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Redox Pioneer: Professor Christine Helen Foyer
del Río, L. A. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4007 · Cited by 9 · see citing works
Ascorbate-regenerating enzymes in chloroplasts.
Hossain, M. S., & Asada, K. (1987) · PubMed · Cited by 9 · see citing works
Non-enzymic catalysis of oxalate decarboxylation by light and flavins
Halliwell, B. B. (1972) · Biochemical Journal · doi:10.1042/bj1290497 · Cited by 7 · see citing works
Self-citationLi, L. (2016) · Reproductive Sciences · doi:10.1177/1933719116667217 · Cited by 7 · see citing works
Quantitative analysis of H2O2 transport through purified membrane proteins
Wang, H., Schoebel, S., Schmitz, F., Dong, H., & Hedfalk, K. (2020) · MethodsX · doi:10.1016/j.mex.2020.100816 · Cited by 7 · see citing works
Redox regulation & sperm function
Mohanty, G., & Samanta, L. (2018) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_242_18 · Cited by 4 · see citing works
Redox Pioneer: Professor Sue Goo Rhee
Levine, R. L., & Chock, P. B. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8137 · Cited by 2 · see citing works
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo
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Self-citationUnderstanding mechanisms of antioxidant action in health and disease
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Self-citationHydroxyl radical is a significant player in oxidative DNA damage in vivo
Halliwell, B. B., Adhikary, A., Dingfelder, M., & Dizdaroğlu, M. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00044f · Cited by 362 · see citing works
Self-citationErgothioneine, recent developments
Cheah, I. K.-M., & Halliwell, B. B. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101868 · Cited by 200 · see citing works
Self-citationDiet-Derived Antioxidants: The Special Case of Ergothioneine
Halliwell, B. B., Tang, R. M. Y., & Cheah, I. K.-M. (2023) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-060822-122236 · Cited by 97 · see citing works
Self-citationErgothioneine: an underrecognised dietary micronutrient required for healthy ageing?
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Ergothioneine and its congeners: anti-ageing mechanisms and pharmacophore biosynthesis
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The physics behind water irregularity
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Barbouti, A., Lаgopati, N., Veroutis, D., Goulas, V., Evangelou, K., Kanavaros, P., Gorgoulis, V. G., & Galaris, D. (2021) · Antioxidants · doi:10.3390/antiox10030491 · Cited by 40 · see citing works
Hydroperoxide-Reducing Enzymes in the Regulation of Free-Radical Processes
Sharapov, M. G., Gudkov, S. V., & Lankin, V. Z. (2021) · Biochemistry (Moscow) · doi:10.1134/s0006297921100084 · Cited by 36 · see citing works
Vascular Aging and Atherosclerosis: A Perspective on Aging
Ma, S., Xie, X., Yuan, R., Xin, Q., Miao, Y., Leng, S. X., Chen, K., & Cong, W. (2024) · Aging and Disease · doi:10.14336/ad.2024.0201-1 · Cited by 33 · see citing works
Pasqualetti, V., Locato, V., Fanali, C., Mulinacci, N., Cimini, S., Morgia, A. M., Pasqua, G., & Gara, L. D. (2021) · Antioxidants · doi:10.3390/antiox10071136 · Cited by 29 · see citing works
Ergothioneine, where are we now?
Halliwell, B. B., & Cheah, I. K.-M. (2022) · FEBS Letters · doi:10.1002/1873-3468.14350 · Cited by 26 · see citing works
Self-citationOral delivery of glutathione: antioxidant function, barriers and strategies
Wei, T., Thakur, S. S., Liu, M., & Wen, J. (2022) · Acta Materia Medica · doi:10.15212/amm-2022-0005 · Cited by 25 · see citing works
Theoretical Study of Antioxidant and Prooxidant Potency of Protocatechuic Aldehyde
Amić, A., Cagardová, D., & Milanović, Ž. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26010404 · Cited by 22 · see citing works
Ramón‐Luing, L. A., Olvera, Y., Flores‐González, J., Palacios, Y., Carranza, C., Aguilar-Duran, Y., Vargas-Hernández, M. A., Gutierrez, N., Quero, K. M., & Chávez‐Galán, L. (2022) · Pathogens · doi:10.3390/pathogens11050492 · Cited by 21 · see citing works
50 shades of oxidative stress: A state-specific cysteine redox pattern hypothesis
Cobley, J. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102936 · Cited by 14 · see citing works
Delgado‐Andrade, C., Olías, R., Marı́n-Manzano, M. C., Seiquer, I., & Clemente, A. (2024) · Antioxidants · doi:10.3390/antiox13010118 · Cited by 21 · see citing works
Mechanism and application prospect of magnesium-based materials in cancer treatment
Ma, Y., Wang, Y., Song, S., Yu, X., Xu, C., Wan, L., Yao, F., Yang, K., Witte, F., & Yang, S. (2025) · Journal of Magnesium and Alloys · doi:10.1016/j.jma.2025.02.010 · Cited by 20 · see citing works
A DFT study of the antioxidant potency of α-tocopherol and its derivatives: PMHC, Trolox, and α-CEHC
Amić, A., & Cagardová, D. (2024) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2024.124796 · Cited by 20 · see citing works
Increased Production of Taxoids in Suspension Cultures of Taxus globosa after Elicitation
Barrales-Cureño, H. J., Ramos-Valdivia, A. C., & Soto‐Hernández, M. (2022) · Future Pharmacology · doi:10.3390/futurepharmacol2010004 · Cited by 19 · see citing works
The Therapeutic Potential of Supersulfides in Oxidative Stress-Related Diseases
Pan, Y., Matsunaga, T., Zhang, T., & Akaike, T. (2025) · Biomolecules · doi:10.3390/biom15020172 · Cited by 16 · see citing works
Preparation, Identification, and Digestive Stability of Antioxidant Peptides From Chlorella vulgaris
Wang, Y., Kong, X., Du, M., Yang, Q., Ye, M., Han, B., & Gan, J. (2024) · Journal of Food Biochemistry · doi:10.1155/2024/3828251 · Cited by 10 · see citing works
Halliwell, B. B. (2022) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2022.109151 · Cited by 10 · see citing works
Self-citationAlfarabi, M., Turhadi, T., Suryowati, T., IMANELI, N. A., & SIHOMBING, P. O. (2022) · Biodiversitas Journal of Biological Diversity · doi:10.13057/biodiv/d230550 · Cited by 10 · see citing works
Liu, W., Halliwell, B. B., & Foyer, C. H. (2025) · Nature Plants · doi:10.1038/s41477-025-02173-9 · Cited by 9 · see citing works
Self-citationLiu, Y., Sun, D.-Z., Chen, K., Zhang, J., Hou, Y., Gao, X.-F., Cai, E., Zhu, H., Zheng, Y., Chen, R., et al. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.105224 · Cited by 8 · see citing works
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Iron and atherosclerosis: Lessons learned from rabbits relevant to human disease
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Self-citationMantelou, A. G., Barbouti, A., GOUSSIA, A. C., Zacharioudaki, A., Papoudou‐Bai, A., Vlachou, C., Kokkoris, S., Papalois, A. E., Galaris, D., & Glantzounis, G. K. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.10.266 · Cited by 6 · see citing works
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Akgun, F. B., TUĞLU, N. S., AÇIL, Y. G., & Eruygur, N. (2023) · Eurasian Journal of Biological and Chemical Sciences · doi:10.46239/ejbcs.1228402 · Cited by 5 · see citing works
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Nahoui-Zarouri, I., Léger, C., Samra, G. E., Cottet‐Rousselle, C., & Moulis, J. (2022) · FEBS Open Bio · doi:10.1002/2211-5463.13527 · Cited by 4 · see citing works
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Reflections of an Aging Free Radical Part 2: Meeting Inspirational People
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Li, L., Ding, D., & Li, P. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1013421 · Cited by 1 · see citing works
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Ofor, C. C., Erejuwa, O. O., Akuodor, G. C., Aja, D. O. J., Mba, A. U., & Shu, E. N. (2022) · International Journal of Basic & Clinical Pharmacology · doi:10.18203/2319-2003.ijbcp20223366
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Yaşlanmada tiyol/disülfür Homeostazisi ve Bazı Mineraller
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Molecular pathophysiology of oxidative metabolism and ion conductivity
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Ergothioneine Thione Spontaneously Binds to and Detaches from the Membrane Interphase
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Pathway optimization for effective heterologous synthesis of ergothioneine in Aspergillus niger
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Halliwell, B. B. (2026) · FEBS Letters · doi:10.1002/1873-3468.70415
Self-citationSpectroscopic Evidence of Free Radicals Generated by Indocyanine Green Under Light Irradiation
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Crop adaptation to climate change: Mechanisms, strategies, and future possibilities
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- Authors
- Halliwell, B.
- Affiliations
- National University of Singapore (SG)
- Corresponding author
- Halliwell, Barry
- ORCID
- Halliwell, Barry
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2020-12
- Volume
- 161
- Pages
- 234-245
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC7550279
- OpenAlex
- W3093319823
- Cited by
- 75
- References
- 171
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 7 · 2023: 16 · 2022: 19 · 2021: 10
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- hydrogen peroxide, reactive oxygen species, catalytic iron, leghemoglobin, oxidative damage, dietary antioxidants, clinical trial failure, iron chelators, ergothioneine, ferroptosis, cytoprotective agents
- MeSH terms
- Aging, Antioxidants, Free Radicals, Humans, Hydrogen Peroxide, Reactive Oxygen Species, Oxidative Stress
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