CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

Jiménez-Garza, Octavio; Baccarelli, Andrea; Byun, Hyang‐Min; Márquez‐Gamiño, Sergio; Barrón-Vivanco, Briscia Socorro; Albores, Arnulfo

doi:10.1016/j.taap.2015.04.016

Cited by 35 publications

(15 citation statements)

References 57 publications

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“…Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes. In the blood from tannery workers exposed to toluene, Jiménez-Garza et al [ 193 ] found significant correlations between airborne levels of toluene and CYP2E1 promoter methylation, as well as IL6 promoter methylation levels. CYP2E1 promoter methylation levels were higher in toluene-exposed smokers compared to non-smokers.…”

Section: Pharmacoepigeneticsmentioning

confidence: 99%

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Cacabelos

Torrellas

2015

IJMS

109

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Epigenetic variability (DNA methylation/demethylation, histone modifications, microRNA regulation) is common in physiological and pathological conditions. Epigenetic alterations are present in different tissues along the aging process and in neurodegenerative disorders, such as Alzheimer’s disease (AD). Epigenetics affect life span and longevity. AD-related genes exhibit epigenetic changes, indicating that epigenetics might exert a pathogenic role in dementia. Epigenetic modifications are reversible and can potentially be targeted by pharmacological intervention. Epigenetic drugs may be useful for the treatment of major problems of health (e.g., cancer, cardiovascular disorders, brain disorders). The efficacy and safety of these and other medications depend upon the efficiency of the pharmacogenetic process in which different clusters of genes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) are involved. Most of these genes are also under the influence of the epigenetic machinery. The information available on the pharmacoepigenomics of most drugs is very limited; however, growing evidence indicates that epigenetic changes are determinant in the pathogenesis of many medical conditions and in drug response and drug resistance. Consequently, pharmacoepigenetic studies should be incorporated in drug development and personalized treatments.

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Section: Pharmacoepigeneticsmentioning

confidence: 99%

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Cacabelos

Torrellas

2015

IJMS

109

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“…The explanation could be, again based on the results of the animal model by Belmont‐Díaz et al [], that increased metabolism by CYP2E1 may have increased the generation of ROSs and electrophilic metabolites such as quinones and epoxides [Cederbaum et al, ; Rappaport et al, ], exceeding the ability of the organism to inactivate them, and hence to excrete them. Contributing to this idea are the results by Jiménez‐Garza et al [] who described that toluene‐exposed workers show hypomethylation in the promoter region of CYP2E1 which is related to an increased expression of mRNA, possibly increasing the activity of the enzyme, thus triggering oxidative stress, as observed above.…”

Section: Discussionmentioning

confidence: 90%

Oxidative stress index is increased in children exposed to industrial discharges and is inversely correlated with metabolite excretion of voc

López-Vargas

Méndez-Serrano²,

Albores-Medina

et al. 2018

Environ and Mol Mutagen

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“…These authors considered a decrease in CYP2E1 activity in TOL exposure to be a health risk, since workers are exposed to other substances that are potentially metabolized by the same CYP isoform. In a study conducted by the same authors, a possible alteration in CYP2E1 gene expression was related to co-exposure to tobacco and TOL (Jiménez-Garza et al, 2015).…”

Section: Discussionmentioning

confidence: 98%

Diazepam influences urinary bioindicator of occupational toluene exposure

Silveira

Albuquerque

Lepera

et al. 2016

Environmental Toxicology and Pharmacology

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In the present study, we investigated the influence of diazepam (DZP) on the excretion of TOL by examining their urinary metabolites, hippuric acid (HA) and ortho-cresol (o-C). Male Wistar rats were exposed to TOL (20ppm) in a nose-only exposure chamber (6h/day, 5days/week for 6 weeks) with simultaneous administration of DZP (10mg/kg/day). Urinary o-C levels were determined by GC-MS, while HA, creatinine (CR), DZP and its metabolite, nordiazepam, were analysed by HPLC-DAD. The results of a Mann-Whitney U test showed that DZP influenced the urinary excretion of o-C (p<0.05). This pioneering study revealed that there was an interaction between DZP and TOL, probably by the inhibition of the CYP isoforms (CYP2B6, CYP2C8, CYP2E1, and CYP1A2) involved in the oxidative metabolism of the solvent. This is relevant information to be considered in the biomonitoring of occupational toluene exposure.

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CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit

Cited by 35 publications

References 57 publications

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Oxidative stress index is increased in children exposed to industrial discharges and is inversely correlated with metabolite excretion of voc

Diazepam influences urinary bioindicator of occupational toluene exposure

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