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Individual and synergistic antioxidative actions of melatonin: studies with vitamin E, vitamin C, glutathione and desferrrioxamine (desferoxamine) in rat liver homogenates
Abstract
The pharmacological effects of melatonin, vitamin E, vitamin C, glutathione and desferrioxamine (desferoxamine) alone and in combination on iron-induced membrane lipid damage in rat liver homogenates were examined by estimating levels of malondialdehyde and 4-hydroxyalkenals (MDA+4-HDA). Individually, melatonin (2.5-1600 microM), vitamin E (0.5-50 microM), glutathione (100-7000 microM) and desferrioxamine (1-8 microM) inhibited lipid peroxidation in a concentration-dependent manner. Vitamin C had both a pro-oxidative (25-2000 microM) and an antioxidative (2600-5000 microM) effect. The IC50 (concentration that reduces damage by 50%) values were 4, 10, 426, 2290 and 4325 microM for vitamin E, desferrioxamine, melatonin, glutathione and vitamin C, respectively. The synergistic actions of melatonin with vitamin C, vitamin E, and glutathione were systematically investigated. When melatonin was combined with vitamin E, glutathione, or vitamin C, the protective effects against iron-induced lipid peroxidation were dramatically enhanced. Even though melatonin was added at very low concentrations, it still showed synergistic effects with other antioxidants at certain concentrations. Furthermore, melatonin not only reversed the pro-oxidative effects of vitamin C, but its efficacy in reducing lipid peroxidation was improved when it was combined with pro-oxidative concentrations of vitamin C. The results provide new information in terms of the possible pharmacological use of the combination of melatonin and classical antioxidants to treat free radical-related conditions.
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“In fact, it has been suggested to be one of the most potent antioxidants because of its ability to scavenge up to 10 reactive oxygen (ROS) and nitrogen species (RNS) with its metabolites compared with most antioxidants, which may only be able to quench a few ROS [16,23,24].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [23]
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
Pineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions*
REITER, R. J. (1991) · Endocrine Reviews · doi:10.1210/edrv-12-2-151 · Cited by 2,192
Self-citationMelatonin : a potent, endogenous hydroxyl radical scavenger
Tan, D. (1993) · Endocrine Journal · Cited by 1,659
Self-citationOxygen-radical absorbance capacity assay for antioxidants
Cao, G., Alessio, H. M., & Cutler, R. G. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90027-r · Cited by 1,612
Enzyme and metabolic inhibitors
Webb, J. L. (1963) · Academic Press eBooks · doi:10.5962/bhl.title.7320 · Cited by 1,529
Actions of Melatonin in the Reduction of Oxidative Stress
Reiter, R. J., Tan, D. X., Osuna, C., & Gitto, E. (2000) · Journal of Biomedical Science · doi:10.1007/bf02253360 · Cited by 1,182
Self-citationOxidative stress and the molecular biology of antioxidant defenses.
Scandalios, J. G. (1997) · Cited by 1,027
Oxidative damage in the central nervous system: protection by melatonin
Reiter, R. J. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00052-5 · Cited by 836
Self-citationMelatonin: A peroxyl radical scavenger more effective than vitamin E
Pieri, C., Marra, M., Moroni, F., Recchioni, R., & Marcheselli, F. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00666-0 · Cited by 735
Mechanisms of Cell Injury by Activated Oxygen Species
Farber, J. L. (1994) · Environmental Health Perspectives · doi:10.2307/3432207 · Cited by 699
Significance of Melatonin in Antioxidative Defense System: Reactions and Products
Tan, D., Manchester, L. C., Reiter, R. J., Qi, W., Karbownik‐Lewińska, M., & Calvo, J. R. (2000) · Neurosignals · doi:10.1159/000014635 · Cited by 566
Self-citationPharmacological actions of melatonin in oxygen radical pathophysiology
Reiter, R. J., Tang, L., García, J. J., & Muñoz‐Hoyos, A. (1997) · Life Sciences · doi:10.1016/s0024-3205(97)00030-1 · Cited by 480
Self-citationTan, D., Manchester, L. C., Reiter, R. J., Plummer, B. F., Limson, J. L., Weintraub, S. T., & Qi, W. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00435-4 · Cited by 471
Self-citationThe Role of Metabolism in the Antioxidant Function of Vitamin E
Liebler, D. C. (1993) · Critical Reviews in Toxicology · doi:10.3109/10408449309117115 · Cited by 353
Urata, Y., Honma, S., Goto, S., Todoroki, S., Iida, T., Cho, S., Honma, K., & Kondo, T. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00131-8 · Cited by 333
Tan, D., Manchester, L. C., Reiter, R. J., Plummer, B. F., Hardies, L. J., Weintraub, S. T., Vijayalaxmi, V., & Shepherd, A. M. M. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9826 · Cited by 319
Self-citationMelatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation
García, J. J., Reiter, R. J., Guerrero, J. M., Escames, G., Yu, B. P., Oh, C. S., & Muñoz‐Hoyos, A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00447-x · Cited by 302
Self-citationAntioxidants in disease mechanisms and therapy
Sies, H. (1997) · Cited by 286
Hardeland, R., Balzer, I., Pöeggeler, B., Fuhrberg, B., Una, H., Behrmann, G., Wolf, R., Meyer, T. J., & Reiter, R. J. (1995) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1995.tb00147.x · Cited by 268
Self-citationVitamin E in health and disease
Canty, Y. (1993) · International Journal of Cardiology · doi:10.1016/0167-5273(93)90032-c · Cited by 243
Antioxidant Defense: Vitamins E and C and Carotenoids
Stahl, W., & Sies, H. (1997) · Diabetes · doi:10.2337/diab.46.2.s14 · Cited by 198
Antioxidant properties of melatonin: a pulse radiolysis study
Mahal, H. S., Sharma, H. S., & Mukherjee, T. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00226-3 · Cited by 167
Glutathione and Glutathione Delivery Compounds
Anderson, M. E. (1996) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60979-5 · Cited by 159
Lipopolysaccharide-induced hepatotoxicity is inhibited by the antioxidant melatonin
Sewerynek, E., Melchiorri, D., Reiter, R. J., Ortíz, G. G., & Lewiñski, A. (1995) · European Journal of Pharmacology Environmental Toxicology and Pharmacology · doi:10.1016/0926-6917(95)90052-7 · Cited by 140
Self-citationQi, W., Reiter, R. J., Tan, D.-X., García, J. J., Manchester, L. C., Karbownik‐Lewińska, M., & Calvo, J. R. (2000) · Environmental Health Perspectives · doi:10.1289/ehp.00108399 · Cited by 123
Self-citationOn the antioxidant activity of melatonin
Antunes, F., Barclay, L. R. C., Ingold, K. U., King, M., Norris, J. Q., Scaiano, J. C., & Xi, F. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00168-3 · Cited by 121
Melatonin protects against stress‐induced gastric lesions by scavenging the hydroxyl radical
Bandyopadhyay, D., Biswas, K., Bandyopadhyay, U., Reiter, R. J., & Banerjee, R. K. (2000) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2000.290303.x · Cited by 100
Self-citationBrain iron delocalization and lipid peroxidation following cardiac arrest
Komara, J. S., Nayini, N. R., Bialick, H. A., Indrieri, R. J., Evans, A. T., Garritano, A. M., Hoehner, T. J., Jacobs, W. A., Huang, R., Krause, G. S., et al. (1986) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(86)80171-8 · Cited by 100
Melatonin protects against gastric ischemia‐reperfusion injury in rats
Alarcón‐de‐la‐Lastra, C., Cabeza, J., Motilva, V., & Martin, M. J. (1997) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1997.tb00334.x · Cited by 99
Scavenging effect of melatonin on hydroxyl radicals generated by alloxan
Brömme, H. J., Mörke, W., Peschke, E., Ebelt, H., & Peschke, D. (2000) · Journal of Pineal Research · doi:10.1034/j.1600-0633.2002.290402.x · Cited by 98
Melatonin and vitamin E limit nitric oxide-induced lipid peroxidation in rat brain homogenates
Escames, G., Guerrero, J. M., Reiter, R. J., García, J. J., Muñoz‐Hoyos, A., Ortíz, G. G., & Oh, C. S. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00498-9 · Cited by 86
Self-citationSiu, A. W., Reiter, R. J., & To, C. H. (1998) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1998.tb00539.x · Cited by 78
Self-citationGoss-Sampson, M. A., MacEvilly, C. J., & Muller, D. P. R. (1988) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(88)90051-2 · Cited by 76
Hara, M., Iigo, M., Ohtani‐Kaneko, R., Nakamura, N., Suzuki, T., Reiter, R. J., & Hirata, K. (1997) · Neurosignals · doi:10.1159/000109113 · Cited by 74
Self-citationBlatt, J., Taylor, S. R., & Kontoghiorghes, G. J. (1989) · PubMed · Cited by 71
Effect of deferoxamine on late deaths following CPR in rats
Kompala, S. D., Babbs, C. F., & Blaho, K. E. (1986) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(86)80175-5 · Cited by 65
Potential of iron chelators as effective antiproliferative agents
Richardson, D. R. (1997) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-75-10-11-1164 · Cited by 61
H2O2 induced lipid peroxidation in rat brain homogenates is greatly reduced by melatonin
Sewerynek, E., Pöeggeler, B., Melchiorri, D., & Reiter, R. J. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11803-5 · Cited by 51
Self-citationPotential of iron chelators as effective antiproliferative agents
Richardson, D. R. (1997) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y97-156 · Cited by 48
New actions of melatonin and their relevance to biometeorology
Hardeland, R. (1997) · International Journal of Biometeorology · doi:10.1007/s004840050053 · Cited by 47
Mechanism of antineuroblastoma activity of deferoxamine in vitro.
Blatt, J., Taylor, S. R., & Stitely, S. (1988) · PubMed · Cited by 47
Viewpoint Does Mega-C Do More Good Than Harm, or More Harm Than Good?
Herbert, V. D. (1993) · Nutrition Today · doi:10.1097/00017285-199301000-00007 · Cited by 41
Tissue Injury by Free Radicals
Cheeseman, K. H. (1993) · Toxicology and Industrial Health · doi:10.1177/0748233793009001-205 · Cited by 30
Biological Antioxidant Defenses
Radí, R. (1993) · Toxicology and Industrial Health · doi:10.1177/0748233793009001-206 · Cited by 19
The Importance of Vitamin E in Human Nutrition
Lloyd, J. K. (1990) · Acta Paediatrica · doi:10.1111/j.1651-2227.1990.tb11322.x · Cited by 18
Free Radicals: Dietary Advantages and DisadvantagesPreprint
Aruoma, O. I. (1997) · Cold Spring Harbor Monograph Archive · doi:10.1101/087969502.34.841 · Cited by 8
Research works printed but not linked: 3
- Chen, 1995, Retinal lipid peroxidation in vitro is inhibited by melatonin, Neurosci. Res. Commun., 17, 151
- Poeggeler, 1995, Melatonin, a mediator of electron transfer and repair reactions, acts synergistically with the chain-breaking antioxidants ascorbate, trolox, and glutathione, Neuroendocrinol. Lett., 17, 87
- Reed, 1993, Interaction of vitamin E, ascorbic acid, and glutathione in protection against oxidative damage, 264
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Reiter, R. J., Mayo, J. C., Tan, D. X., Sainz, R. M., Alatorre-Jiménez, M. A., & Qin, L. (2016) · Journal of Pineal Research · doi:10.1111/jpi.12360 · Cited by 1,777
Self-citationMelatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism
Tan, D.-X., Manchester, L., Esteban-Zubero, E., Zhou, Z., & Reiter, R. (2015) · Molecules · doi:10.3390/molecules201018886 · Cited by 719
Self-citationHardeland, R. (2005) · Endocrine · doi:10.1385/endo:27:2:119 · Cited by 680
Melatonin enhances plant growth and abiotic stress tolerance in soybean plants
Wei, W., Li, Q., Chu, Y.-N., Reiter, R. J., Yu, X.-M., Zhu, D.-H., Zhang, W., Ma, B., Lin, Q. F., Zhang, J.-S., et al. (2014) · Journal of Experimental Botany · doi:10.1093/jxb/eru392 · Cited by 660
Self-citationTan, D. X., Manchester, L. C., Liu, X., Rosales‐Corral, S., Acuña-Castroviejo, D., & Reiter, R. J. (2012) · Journal of Pineal Research · doi:10.1111/jpi.12026 · Cited by 584
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Metadata
- Authors
- Gitto, E., Tan, D.-X., Reiter, R. J., Karbownik, M., Manchester, L. C., Cuzzocrea, S., Fulia, F., & Barberi, I.
- Affiliations
- University of Messina (IT)
- Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio , San Antonio, Texas,
- The University of Texas at San Antonio Health Science Center (US)
- Department of Thyroidology, Institute of Endocrinology, Medical University of Lódz ,
- Corresponding author
- Reiter, Russel J
- Venue
- Journal of Pharmacy and Pharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-10-01
- Volume
- 53
- Issue
- 10
- Pages
- 1393-1401
- ISSN
- 0022-3573 (ISSN-L)
- 2042-7158
- OpenAlex
- W1983478689
- Cited by
- 196
- References
- 52
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 11 · 2023: 12 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 4 · 2018: 11 · 2017: 13 · 2016: 11 · 2015: 9 · 2014: 13 · 2013: 7 · 2012: 9
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Pharmacy and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Keywords
- melatonin, vitamin E, vitamin C, glutathione, deferoxamine, lipid peroxidation, synergistic antioxidant effect, pro-oxidant activity, malondialdehyde, 4-hydroxyalkenals, liver homogenate, free radicals
- MeSH terms
- Animals, Antioxidants, Ascorbic Acid, Cell Membrane, Deferoxamine, Dose-Response Relationship, Drug, Drug Synergism, Glutathione, Lipids, Malondialdehyde, Melatonin, Proteins, Vitamin E, Lipid Peroxidation, Rats, In Vitro Techniques
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