ArticleAging2021
Dexmedetomidine reverses MTX-induced neurotoxicity and inflammation in hippocampal HT22 cell lines via NCOA4-mediated ferritinophagy.
Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Nanodrug delivery systems targeting ferroptosis as an innovative therapeutic approach for Rheumatoid Arthritis.Materials today. Bio · 2025Review
- Interactions Between Ferroptosis and Oxidative Stress in Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2024Review
- Dexmedetomidine mitigates lidocaine-induced spinal cord injury by repressing ferritinophagy-mediated ferroptosis by increasing CISD2 expression in rat models.Journal of bioenergetics and biomembranes · 2024Article
- Impact of dexmedetomidine-assisted anesthesia in elderly patients undergoing radical resection of colon cancer.World journal of gastrointestinal surgery · 2024Article
- Ferritinophagy and Ferroptosis in Cerebral Ischemia Reperfusion Injury.Neurochemical research · 2024Review
- Ferritinophagy-Mediated Hippocampus Ferroptosis is Involved in Cognitive Impairment in Immature Rats Induced by Hypoxia Combined with Propofol.Neurochemical research · 2024Article
- Cinnamic acid mitigates methotrexate-induced lung fibrosis in rats: comparative study with pirfenidone.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Article
- Dexmedetomidine Attenuates Methotrexate-Induced Neurotoxicity and Memory Deficits in Rats through Improving Hippocampal Neurogenesis: The Role of miR-15a/ROCK-1/ERK1/2/CREB/BDNF Pathway Modulation.International journal of molecular sciences · 2023Article
- Identification and Validation of Ferroptosis-Related Genes in Sevoflurane-Induced Hippocampal Neurotoxicity.Oxidative medicine and cellular longevity · 2022Article
- Ferroptosis in inflammatory arthritis: A promising future.Frontiers in immunology · 2022Review
- Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation.International journal of biological sciences · 2022Article
- Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway.Molecular medicine reports · 2021Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The incidence of chemotherapy-induced cognitive impairment (CICI) has attracted massive attention. Some studies have demonstrated the neuroprotective effects of dexmedetomidine (DEX). Here, alterations in nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy were investigated as the possible causes of DEX's neuroprotection of HT22 cells against methotrexate (MTX)-induced neurotoxicity. We used various concentrations of DEX and NCOA4-siRNA to treat MTX-induced neurotoxicity and inflammation in HT22 cells. The biomarkers of HT22 cells viability, apoptosis and inflammatory were tested. The expression of ferritinophagy markers were detected in the HT22 cells by using western blot and Immunofluorescence. We found that 10 and 50 ng/mL of DEX alleviated MTX-induced hippocampal neuronal inflammatory injuries. Meanwhile, DEX also reversed MTX-induced iron and ROS overproduction. Increasing DEX concentrations caused significant falls in the expression of ferritin heavy chain 1 (FTH1). DEX also increased vital ferritinophagy markers, NCOA4 and LC3II. NCOA4-siRNA transfection annulled the neuroprotective effects of DEX on MTX-induced inflammation in HT22 cells. Additionally, because NCOA4-siRNA disrupted ferritinophagy, DEX's inhibitory impact on MTX-induced iron and ROS overproduction in HT22 cells was also annihilated. DEX weakened MTX-provoked neurontoxicity in HT22 cells, possibly by improving NCOA4-mediated ferritinophagy. Our discoveries present further mechanisms for understanding the protective effects of DEX against MTX-induced cognitive impairment.
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