ArticleCells2022
Activation of MT1/MT2 to Protect Testes and Leydig Cells against Cisplatin-Induced Oxidative Stress through the SIRT1/Nrf2 Signaling Pathway.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.Frontiers in endocrinology · 2023Pooled it
- Ramelteon and Mortality in Patients With Sepsis and Cancer: Insights From a Propensity-Matched Analysis of the MIMIC-IV Database.Cancer medicine · 2026Article
- Ginsenoside Re Attenuates D-Galactose-Induced Aging-like Oxidative Stress in Cultured Bovine Oocytes via Activation of the SIRT1/Nrf2 Signaling Pathway.International journal of molecular sciences · 2026Article
- Review
- Molecular Characterization of Melatonin Receptors inAntioxidants (Basel, Switzerland) · 2026Article
- Male testosterone synthesis disorders: oxidative stress pathways, regulatory mechanisms, potential of antioxidant therapy, and botanical medicine prospects.Asian journal of andrology · 2026Review
- Febuxostat alleviates testicular dysfunction induced by cyclophosphamide in rats via modulation of pyroptosis and mTOR autophagy axis.Scientific reports · 2026Article
- Arab gum coating enhances the bioavailability and therapeutic potential of nanoselenium in cisplatin-induced testicular toxicity.Scientific reports · 2026Article
- Diacerein mitigates cisplatin-induced testicular toxicity in rats; Role of Nrf2/ HO-1, NF-κB/caspase-3 and NLRP3/ASC/Caspase-1 signaling pathways.Molecular biology reports · 2026Article
- Review
- Yam-Active Protein Protects Against Cyclophosphamide-Induced Testicular Injury by Suppressing Inflammatory Responses.Molecules (Basel, Switzerland) · 2026Article
- Micronutrient antioxidant supplementation alleviates valproic acid-induced oxidative stress and male infertility via the NRF2/HO-1 pathway.Redox biology · 2025Article
- Melatonin Synergises the Chemotherapeutic Effect of Temozolomide in Glioblastoma by Suppressing NF-κB/COX-2 Signalling Pathways.Journal of cellular and molecular medicine · 2025Article
- Morin hydrate protects against cisplatin-induced testicular toxicity by modulating ferroptosis and steroidogenesis genes' expression and upregulating Nrf2/Heme oxygenase-1.Scientific reports · 2025Article
- Oral administration of antimicrobial peptide MPX can effectively regulate LPS-mediated testicular oxidative stress and blood‒testis barrier damage.Scientific reports · 2025Article
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- Resveratrol alleviates testicular toxicity induced by anti-PD-1 through regulating the NRF2-SLC7A11-GPX4 pathway.Frontiers in immunology · 2025Article
- Mechanism of salidroside promoting testosterone secretion induced by HFrontiers in chemistry · 2025Article
- Therapeutic Aspects of Melatonin-sirtuin Crosstalk: An Updated Review of Current Data Based on Cellular Mechanisms.Current drug targets · 2025Review
- Melatonin in Chemo/Radiation Therapy; Implications for Normal Tissues Sparing and Tumor Suppression: An Updated Review.Current medicinal chemistry · 2025Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is growing concern that chemotherapy drugs can damage Leydig cells and inhibit the production of testosterone. Increasing evidence shows that melatonin benefits the reproductive process. This study mainly explores the protective effect and possible molecular mechanism of melatonin regarding cisplatin-induced oxidative stress in testicular tissue and Leydig cells. We found that there were only Leydig and Sertoli cells in the testes of gastrointestinal tumor patients with azoospermia caused by platinum chemotherapeutic drugs. Melatonin (Mel) receptor 1/melatonin receptor 2 (MT1/MT2) was mainly expressed in human and mouse Leydig cells of the testes. We also observed that the melatonin level in the peripheral blood decreased and oxidative stress occurred in mice treated with cisplatin or gastrointestinal tumor patients treated with platinum-based chemotherapeutic drugs. iTRAQ proteomics showed that SIRT1/Nrf2 signaling and MT1 proteins were downregulated in cisplatin-treated mouse testes. The STRING database predicted that MT1 might be able to regulate the SIRT1/Nrf2 signaling pathway. Melatonin reduced oxidative stress and upregulated SIRT1/Nrf2 signaling in cisplatin-treated mouse testes and Leydig cells. Most importantly, after inhibiting MT1/MT2, melatonin could not upregulate SIRT1/Nrf2 signaling in cisplatin-treated Leydig cells. The MT1/MT2 inhibitor aggravated the cisplatin-induced downregulation of SIRT1/Nrf2 signaling and increased the apoptosis of Leydig cells. We believe that melatonin stimulates SIRT1/Nrf2 signaling by activating MT1/MT2 to prevent the cisplatin-induced apoptosis of Leydig cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.