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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Melatonin has been suggested to be one of the most potent antioxidants because of its ability to scavenge up to 10 reactive oxygen and nitrogen species with its metabolites compared with most antioxidants, which may only be able to quench a few ROS.
“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]
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- 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 › Antioxidant Activity and Oxidative Stress
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Biochemistry › 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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