ArticleBMC neuroscience2012
Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons.
Article in BMC neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- Metformin's therapeutic potential in spinal cord injury: a systematic review and meta-analysis on locomotor recovery, neuropathic pain alleviation, and modulation of secondary injury mechanisms.Acta neurochirurgica · 2025Pooled it
- Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials.BMC medicine · 2022Pooled it
- Metformin exacerbates diabetic amyotrophy via oxidative stress and gut microbiota alterations.Frontiers in microbiology · 2026Article
- Metformin Improves Spatial Memory and Reduces Seizure Severity in a Rat Model of Epilepsy and Alzheimer's Disease comorbidity via PI3K/Akt Signaling Pathway.Molecular neurobiology · 2025Article
- Neuroprotective role of Nigella Sativa seed oil in mitigating bisphenol a-induced neurodegeneration.Scientific reports · 2025Article
- Metformin Protects Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons from Oxidative Damage Through Antioxidant Mechanisms.Neurotoxicity research · 2025Article
- Hydrogen Sulfide Alleviates Schizophrenia-Like Behavior Through Regulating Apoptosis by S-Sulfhydrylation Modification.CNS neuroscience & therapeutics · 2025Article
- Nonconceptus Mechanisms of Prenatal Alcohol Exposure That Disrupt Embryo-Fetal Development: An Integrative View.Alcohol research : current reviews · 2025Review
- Oxidative Effects in Early Stages of Embryo Development Due to Alcohol Consumption.International journal of molecular sciences · 2024Review
- Mito-metformin protects against mitochondrial dysfunction and dopaminergic neuronal degeneration by activating upstream PKD1 signaling in cell culture and MitoPark animal models of Parkinson's disease.Frontiers in neuroscience · 2024Article
- Outward depolarization of the microglia mitochondrial membrane potential following lipopolysaccharide exposure: a novel screening tool for microglia metabolomics.Frontiers in cellular neuroscience · 2024Article
- The comparative effectiveness of metformin and risperidone in a rat model of valproic acid-induced autism, Potential role for enhanced autophagy.Psychopharmacology · 2023Article
- Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin.Antioxidants (Basel, Switzerland) · 2023Article
- Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer's disease.Heliyon · 2022Review
- Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs.Frontiers in aging · 2022Review
- Thymoquinone Potentiates the Effect of Phenytoin against Electroshock-Induced Convulsions in Rats by Reducing the Hyperactivation of m-TOR Pathway and Neuroinflammation: Evidence from In Vivo, In Vitro and Computational Studies.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function.Liver research (Beijing, China) · 2021Article
- Neuroprotective Effects of Curcumin in Methamphetamine-Induced Toxicity.Molecules (Basel, Switzerland) · 2021Article
- Metformin Protects Myelin from Degeneration in A Mouse Model of Iysophosphatidylcholine-Induced Demyelination in The Optic Chiasm.Cell journal · 2021Article
- Metformin Preserves Peripheral Nerve Damage with Comparable Effects to Alpha Lipoic Acid in Streptozotocin/High-Fat Diet Induced Diabetic Rats.Diabetes & metabolism journal · 2020Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met) and thymoquinone (TQ) during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD) 17.5.
resultsWe found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM) exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca²⁺]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (ΔψM), which is typically lowered by ethanol exposure. Increased cytosolic free [Ca²⁺]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2), increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death.
conclusionThese findings suggested that Met and TQ are strong protective agents against ethanol-induced neuronal apoptosis in primary rat cortical neurons. The collective data demonstrated that Met and TQ have the potential to ameliorate ethanol neurotoxicity and revealed a possible protective target mechanism for the damaging effects of ethanol during early brain development.
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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 Socratic graph.