The former popular hypnotic chloral hydrate has been known to spontaneously condense with tryptamine in the body to give rise to a highly unpolar 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) derivative. Earlier studies have revealed the relative permeability of the molecule through the body, and its ability to induce Parkinson-like symptoms in rats. In this study, we report that TaClo is a highly cytotoxic agent that leads to apoptosis in human neuroblastoma cells involving caspase-3 activation.
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Trichloroethylene and its metabolite TaClo lead to degeneration of substantia nigra dopaminergic neurones: Effects in wild type and human A30P mutant α-synuclein mice.
Neurosci Lett
October 2019
Medical Toxicology Centre, Wolfson Building, Newcastle University, Claremont Place, Newcastle-Upon Tyne, NE2 4AA, UK; Institute for Neuroscience, Newcastle University, Cookson Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK; Alzheimer's Society Doctoral Training Centre, Newcastle University, Edwardson Building, Newcastle upon Tyne, NE4 5PL, UK. Electronic address:
Parkinson's disease (PD) is characterised pathologically by degeneration of the dopaminergic (DA) neurones of the substantia nigra pars compacta (SNpc) and the presence of α-synuclein containing Lewy body inclusions. Trichloroethylene (TCE) has been suggested as a potential environmental chemical that may contribute to the development of PD, via conversion to the neurotoxin, 1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo). We investigated the effect of an 8 week exposure to TCE or TaClo on wild type and, as an experimental model of PD, A30P mutant α-synuclein overexpressing mice using a combination of behaviour and pathology.
View Article and Find Full Text PDF1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation.
Oxid Med Cell Longev
July 2019
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
Several studies have revealed the neurotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo). However, the underlying mechanism has not been completely elucidated, particularly . This study was designed to study the neurotoxicity of TaClo by stereotactically injecting TaClo into the striatum of Wistar rats.
View Article and Find Full Text PDFTrichloroethylene and Parkinson's Disease: Risk Assessment.
Mol Neurobiol
July 2018
Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.
This study was conducted to investigate the mechanism of action and extent of selective dopaminergic neurodegeneration caused by exposure to trichloroethylene (TCE) leading to the endogenous formation of the neurotoxin 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in rodents. Beginning at 3 months of age, male C57BL/6 mice received oral TCE dissolved in vehicle for 8 months. Dopaminergic neuronal loss was assessed by nigral tyrosine hydroxylase (TH) immunoreactivity.
View Article and Find Full Text PDF1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Alters Cell Cycle Progression in Human Neuroblastoma Cell Lines.
Neurotox Res
November 2017
Neuroinflammation Research Group, South Asian University, Chanakyapuri, New Delhi, India.
1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline, abbreviated as TaClo, is an endogenous neurotoxin capable of formation in the brain through the condensation of neuronal tryptamine with ingested exogenous toxins such as trichloroethylene or chloral hydrate. Due to its structural resemblance to 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and similar ability to inhibit mitochondrial complex I, TaClo has been implicated in the etiology of Parkinson's disease. Previous studies have shown the cytotoxicity of TaClo in various cell culture models.
View Article and Find Full Text PDFBasic studies on epigenetic carcinogenesis of low-dose exposure to 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) in vitro.
PLoS One
August 2017
Department of Agricultural and Biological Engineering, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, United States of America.
1-Trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) has been widely studied as a neurotoxic substance, however, only few reports have explored its effect on carcinogenicity. Since the aberrant modification of DNA methylation occurs very early in almost all human cancers, the focus of this study is to assess the carcinogenicity of TaClo by characterizing alterations of the epigenetic state, specifically, DNA methylation, upon exposure to TaClo in a HEK 293 model cell line. Our results suggest that TaClo could induce global DNA hypomethylation and transcriptional repression of critical tumor suppressor genes by increasing their promoter methylation.
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