ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Melatonin Improves mitochondrial function by promoting MT1/SIRT1/PGC-1 alpha-dependent mitochondrial biogenesis in cadmium-induced hepatotoxicity in vitro.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 129 citations in OpenAlex.
- Effect of Intracoronary and Intravenous Melatonin on Myocardial Salvage Index in Patients with ST-Elevation Myocardial Infarction: a Randomized Placebo Controlled Trial.Journal of cardiovascular translational research · 2017Trial
- The Molecular and Cellular Mechanisms of Melatonin: From Physiological Actions to Clinical Applications in Reproductive Medicine.International journal of molecular sciences · 2026Review
- Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.Molecules (Basel, Switzerland) · 2026Review
- The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.Antioxidants (Basel, Switzerland) · 2026Review
- Circadian Influences on Chronic Kidney Disease Progression: Molecular Signaling Pathways of Melatonin and Their Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Understanding molecular mechanisms driving cadmium-induced mitochondrial dysfunction in human metabolic liver disease.Environmental toxicology and pharmacology · 2026Review
- Melatonin in Integrative Oncology: Biological Mechanisms, Therapeutic Evidence and Implementation Strategies.Oncology research · 2026Review
- Sulforaphane attenuates oxidative stress, senescence, and ferroptosis induced by cigarette smoke extractResearch in pharmaceutical sciences · 2025Article
- Hypoxia reverses the early anti-inflammatory microglial response to the β-amyloid peptide: mitochondrial involvement and beneficial roles of melatonin and naringenin.Journal of translational medicine · 2025Article
- Exosome miR-152-3p derived from small intestinal epithelium modulates aging process in adipocytes.3 Biotech · 2025Article
- Therapeutic Aspects of Melatonin-sirtuin Crosstalk: An Updated Review of Current Data Based on Cellular Mechanisms.Current drug targets · 2025Review
- Sulforaphane Exposure Prevents Cadmium-Induced Toxicity and Mitochondrial Dysfunction in the NematodeAntioxidants (Basel, Switzerland) · 2024Article
- Luteolin Alleviates Cadmium-Induced Kidney Injury by Inhibiting Oxidative DNA Damage and Repairing Autophagic Flux Blockade in Chickens.Antioxidants (Basel, Switzerland) · 2024Article
- Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model.Neural regeneration research · 2024Article
- Melatonin regulates the circadian rhythm to ameliorate postoperative sleep disorder and neurobehavioral abnormalities in aged mice.CNS neuroscience & therapeutics · 2024Article
- Melatonin Activates Anti-Inflammatory Features in Microglia in a Multicellular Context: Evidence from Organotypic Brain Slices and HMC3 Cells.Biomolecules · 2023Article
- The Role of Sirtuins in Sarcopenia and Frailty.Aging and disease · 2023Article
- Review
- Melatonin, a natural antioxidant therapy in spinal cord injury.Frontiers in cell and developmental biology · 2023Review
- Mitochondrial signal transduction.Cell metabolism · 2022Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melatonin is an indolamine synthesized in the pineal gland that has a wide range of physiological functions, and it has been under clinical investigation for expanded applications. Increasing evidence demonstrates that melatonin can ameliorate cadmium-induced hepatotoxicity. However, the potentially protective effects of melatonin against cadmium-induced hepatotoxicity and the underlying mechanisms of this protection remain unclear. This study investigates the protective effects of melatonin pretreatment on cadmium-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. We exposed HepG2 cells to different concentrations of cadmium chloride (2.5, 5, and 10 μM) for 12 h. We found that Cd stimulated cytotoxicity, disrupted the mitochondrial membrane potential, increased reactive oxygen species production, and decreased mitochondrial mass and mitochondrial DNA content. Consistent with this finding, Cd exposure was associated with decreased Sirtuin 1 (SIRT1) protein expression and activity, thus promoted acetylation of PGC-1 alpha, a key enzyme involved in mitochondrial biogenesis and function, although Cd did not disrupt the interaction between SIRT1 and PGC-1 alpha. However, all cadmium-induced mitochondrial oxidative injuries were efficiently attenuated by melatonin pretreatment. Moreover, Sirtinol and SIRT1 siRNA each blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT1/ PGC-1 alpha signaling. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to promote SIRT1/ PGC-1 alpha signaling. In summary, our results indicate that SIRT1 plays an essential role in the ability of moderate melatonin to stimulate PGC-1 alpha and improve mitochondrial biogenesis and function at least partially through melatonin receptors in cadmium-induced hepatotoxicity.
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