ArticleHeliyon2024
Melatonin mitigates doxorubicin induced chemo brain in a rat model in a NRF2/p53-SIRT1 dependent pathway.
Article in Heliyon, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Mechanistic insights and therapeutic interventions of mitochondrial quality control in chemotherapy-related cognitive impairment.Neoplasia (New York, N.Y.) · 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
- Doxorubicin Toxicity and Recent Approaches to Alleviating Its Adverse Effects with Focus on Oxidative Stress.Molecules (Basel, Switzerland) · 2025Review
- Melatonin Synergises the Chemotherapeutic Effect of Temozolomide in Glioblastoma by Suppressing NF-κB/COX-2 Signalling Pathways.Journal of cellular and molecular medicine · 2025Article
- Different Mechanisms in Doxorubicin-Induced Neurotoxicity: Impact of BRCA Mutations.International journal of molecular sciences · 2025Review
- Protective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Adjunctive effects of intermittent fasting and exercise with glibenclamide on diabetic nephropathy in rats: a potential role of the polyol pathway.Frontiers in physiology · 2025Article
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Authors and funding
8 authors.
Funding
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Abstract
Cancer is a critical health problem, and chemotherapy administration is mandatory for its eradication. However, chemotherapy like doxorubicin (Dox) has serious side-effects including cognitive impairment or chemo brain. Melatonin is a neuroprotective agent that has antioxidant, and anti-inflammatory effects. We aimed to explore melatonin's effect on Dox-induced chemo brain to discover new mechanisms associated with Dox-induced neurotoxicity and try to prevent its occurrence. Thirty-two male albino rats had been equally divided into four groups; control, melatonin-administrated, Dox-induced chemo brain, and melatonin + Dox treated. On the 9th day, brain had been excised after scarification and had been assessed for reactive oxygen species measurement, histopathological analysis, immunohistochemical, gene and protein expressions for the nuclear factor erythroid 2-related factor 2 (Nrf2), p53 and Silent information regulator 2 homolog 1 (SIRT1). Our results show that melatonin coadministration diminished Dox induced hippocampal and prefrontal cortex (PFC) cellular degeneration. It alleviated Nitric Oxide (NO) level and reversed the decline of antioxidant enzyme activities. It also upregulated Nrf2, SIRT1 and downregulated p53 gene expression in rats receiving Dox. Moreover, melatonin elevated the protein expression level of Nrf2, SIRT1 and reduced p53 corresponding to immunohistochemical results. The data suggested that melatonin can mitigate Dox-induced neurotoxicity by aggravating the endogenous antioxidants and inducing neurogenesis through activation of Nrf2/p53-SIRT1signaling pathway in adult rats' PFC. These effects were associated with Nrf2, SIRT1 activation and p53 inhibition. This could be guidance to add melatonin as an adjuvant supplement to Dox regimens to limit its adverse effect on the brain function.
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