ArticleNeurotoxicity research2017
On the Role of DT-Diaphorase Inhibition in Aminochrome-Induced Neurotoxicity In Vivo.
Article in Neurotoxicity research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Neuromelanin-induced cellular stress and neurotoxicity in the pathogenesis of Parkinson's disease.Apoptosis : an international journal on programmed cell death · 2025Review
- Protective Effects of Flavonoid Rutin Against Aminochrome Neurotoxicity.Neurotoxicity research · 2023Article
- Aminochrome Induces Neuroinflammation and Dopaminergic Neuronal Loss: A New Preclinical Model to Find Anti-inflammatory and Neuroprotective Drugs for Parkinson's Disease.Cellular and molecular neurobiology · 2023Article
- The diverse functionality of NQO1 and its roles in redox control.Redox biology · 2021Review
- Addressing the Selectivity of Enzyme Biosensors: Solutions and Perspectives.Sensors (Basel, Switzerland) · 2021Review
- Cellular Trafficking of Glutathione Transferase M2-2 Between U373MG and SHSY-S7 Cells is Mediated by Exosomes.Neurotoxicity research · 2021Article
- Cancer-associated variants of human NQO1: impacts on inhibitor binding and cooperativity.Bioscience reports · 2019Article
- On the Role of Aminochrome in Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Parkinson's Disease.Frontiers in neuroscience · 2019Article
- Dopamine: Functions, Signaling, and Association with Neurological Diseases.Cellular and molecular neurobiology · 2019Review
- Neurotoxins as Preclinical Models for Parkinson's Disease.Neurotoxicity research · 2018Review
- Aminochrome Induces Irreversible Mitochondrial Dysfunction by Inducing Autophagy Dysfunction in Parkinson's Disease.Frontiers in neuroscience · 2018Article
- On the role of endogenous neurotoxins and neuroprotection in Parkinson's disease.Neural regeneration research · 2017Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dopamine oxidation in the pathway leading to neuromelanin formation generates the ortho-quinone aminochrome, which is potentially neurotoxic but normally rapidly converted by DT-diaphorase to nontoxic leukoaminochrome. However, when administered exogenously into rat striatum, aminochrome is able to produce damage to dopaminergic neurons. Because of a recent report that substantia nigra pars compacta (SNpc) tyrosine hydroxylase (T-OH) levels were unaltered by aminochrome when there was cell shrinkage of dopaminergic neurons along with a reduction in striatal dopamine release, the following study was conducted to more accurately determine the role of DT-diaphorase in aminochrome neurotoxicity. In this study, a low dose of aminochrome (0.8 nmol) with or without the DT-diaphorase inhibitor dicoumarol (0.2 nmol) was injected into the left striatum of rats. Intrastriatal 6-hydroxydopamine (6-OHDA, 32 nmol) was used as a positive neurotoxin control in other rats. Two weeks later, there was significant loss in numbers of T-OH immunoreactive fibers in SNpc, also a loss in cell density in SNpc, and prominent apomorphine (0.5 mg/kg sc)-induced contralateral rotations in rats that had been treated with aminochrome, with aminochrome/dicoumarol, or with 6-OHDA. Findings demonstrate that neurotoxic aminochrome is able to exert neurotoxicity only when DT-diaphorase is suppressed-implying that DT-diaphorase is vital in normally suppressing toxicity of in vivo aminochrome, generated in the pathway towards neuromelanin formation.
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