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Melatonin mitigates oxidative damage induced by anthracycline: a systematic-review and meta-analysis of murine models
Andrea Faggiano1,2, Elisa Gherbesi1, Ashot Avagimyan3
1Department of Cardio-Thoracic-Vascular Diseases, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Background:
Oxidative stress induced by the excessive production of reactive oxygen species is one of the primary mechanisms implicated in anthracycline (ANT)-induced cardiotoxicity. There is a strong clinical need for a molecule capable of effectively preventing and reducing the oxidative damage caused by ANT. In vitro and in vivo studies conducted in mice have shown that melatonin stimulates the expression of antioxidative agents and reduces lipid peroxidation induced by ANT.
Methods:
We investigated this issue through a meta-analysis of murine model studies. The outcome of the meta-analysis was to compare oxidative damage, estimated by products of lipid peroxidation (MDA = Malondialdehyde) and markers of oxidative stress (SOD = Superoxide Dismutase, GSH = Glutathione), along with a marker of cardiac damage (CK-MB = creatine kinase-myocardial band), assessed by measurements in heart and/or blood samples in mice undergoing ANT chemotherapy and assuming melatonin vs. controls. The PubMed, OVID-MEDLINE and Cochrane library databases were analysed to search English-language review papers published from the inception up to August 1st, 2023. Studies were identified by using Me-SH terms and crossing the following terms: "melatonin", "oxidative stress", "lipid peroxidation", "anthracycline", "cardiotoxicity".
Results:
The metanalysis included 153 mice administered melatonin before, during or immediately after ANT and 153 controls from 13 studies. Compared with controls, the levels of all oxidative stress markers were significantly better in the pooled melatonin group, with standardized mean differences (SMD) for MDA, GSH and SOD being -8.03 ± 1.2 (CI: -10.43/-5.64, p < 0.001), 7.95 ± 1.8 (CI: 4.41/11.5, p < 0.001) and 3.94 ± 1.6 (CI: 0.77/7.12, p = 0.015) respectively. Similarly, compared with controls, CK-MB levels reflecting myocardial damage were significantly lower in the pooled melatonin group, with an SMD of -4.90 ± 0.5 (CI: -5.82/-3.98, p < 0.001).
Conclusion:
Melatonin mitigates the oxidative damage induced by ANT in mouse model. High-quality human clinical studies are needed to further evaluate the use of melatonin as a preventative/treatment strategy for ANT-induced cardiotoxicity.
Insights
Melatonin effectively reduces oxidative stress and lipid peroxidation in mice treated with anthracyclines (ANT), significantly lowering markers of cardiotoxicity. Further human studies are needed to confirm its clinical use for preventing ANT-induced heart damage.
Area of Science:
- Biomedical Science
- Pharmacology
- Toxicology
Background:
- Anthracycline (ANT) chemotherapy can cause cardiotoxicity due to excessive reactive oxygen species production.
- Melatonin has demonstrated potential in vitro and in vivo to counteract ANT-induced oxidative damage.
- A clinical need exists for effective strategies to prevent or mitigate ANT-induced cardiotoxicity.
Purpose of the Study:
- To conduct a meta-analysis evaluating melatonin's efficacy in reducing oxidative damage and cardiotoxicity in murine models treated with anthracyclines.
- To compare oxidative stress markers (MDA, GSH, SOD) and cardiac damage marker (CK-MB) in mice receiving melatonin versus control groups.
Main Methods:
- Meta-analysis of 13 murine studies, including 153 mice in the melatonin group and 153 controls.
- Searched PubMed, OVID-MEDLINE, and Cochrane Library databases for English-language papers up to August 2023.
- Utilized MeSH terms and keywords: "melatonin", "oxidative stress", "lipid peroxidation", "anthracycline", "cardiotoxicity".
Main Results:
- Melatonin administration significantly improved all measured oxidative stress markers compared to controls.
- Standardized Mean Differences (SMD) showed significant reductions in MDA (-8.03) and increases in GSH (7.95) and SOD (3.94) with melatonin.
- Cardiac damage marker CK-MB was significantly lower in the melatonin group (SMD -4.90).
Conclusions:
- Melatonin effectively mitigates anthracycline-induced oxidative damage and cardiotoxicity in a mouse model.
- High-quality human clinical trials are necessary to validate melatonin as a preventative or therapeutic agent for anthracycline cardiotoxicity.
