Lead (Pb) and neurodevelopment: A review on exposure and biomarkers of effect (BDNF, HDL) and susceptibility

In many subjects who are genetically susceptible to asthma, exposure to environmental stimuli may exacerbate their condition. However, it is unknown how the expression and function of a family of pattern-recognition receptors called toll-like receptors (TLR) are affected by exposure to particulate pollution. TLRs serve a critical function in alerting the immune system of tissue damage or infection—the so-called “danger signals”. We are interested in the role that TLRs play in directing appropriate responses by innate immunity, particularly dendritic cells (DC), after exposing them to particulate pollution. Dendritic cells serve a pivotal role in directing host immunity. Thus, we hypothesized that alterations in TLR expression could be further explored as potential biomarkers of effect related to DC exposure to particulate pollution. We show some preliminary data that indicates that inhaled particulate pollution acts directly on DC by down-regulating TLR expression and altering the activation state of DC. While further studies are warranted, we suggest that alterations in TLR2 and TLR4 expression should be explored as potential biomarkers of DC exposure to environmental particulate pollution.

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Human exposure to metals. Pathways of exposure, biomarkers of effect, and host factors

Ecotoxicology and Environmental Safety ◽

10.1016/s0147-6513(03)00053-8 ◽

2003 ◽

Vol 56 (1) ◽

pp. 93-103 ◽

Cited By ~ 69

Author(s):

Jaqueline Calderón ◽

Deogracias Ortiz-Pérez ◽

Leticia Yáñez ◽

Fernando Dı́az-Barriga

Keyword(s):

Human Exposure ◽

Host Factors ◽

Exposure Biomarkers ◽

Biomarkers Of Effect

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Biomarkers of effect in evaluating dithianon cocarcinogenesis: selective induction and suppression of murine CYP3A isoform

Cancer Letters ◽

10.1016/s0304-3835(97)04711-3 ◽

1997 ◽

Vol 113 (1-2) ◽

pp. 221-228 ◽

Cited By ~ 7

Author(s):

M. Paolini ◽

R. Mesirca ◽

L. Pozzettia ◽

A. Sapone ◽

G. Cantelli-Forti

Keyword(s):

Biomarkers Of Effect

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Biological and Functional Changes in Healthy Adult Smokers Who Are Continuously Abstinent From Smoking for One Year: Protocol for a Prospective, Observational, Multicenter Cohort Study (Preprint)

10.2196/preprints.12138 ◽

2018 ◽

Author(s):

Cam Tuan Tran ◽

Loyse Felber Medlin ◽

Nicola Lama ◽

Brindusa Taranu ◽

Weeteck Ng ◽

...

Keyword(s):

Cohort Study ◽

Adverse Events ◽

Clinical Chemistry ◽

Risk Level ◽

Functional Changes ◽

Biomarkers Of Exposure ◽

Quit Smoking ◽

Study Results ◽

Biomarkers Of Effect

BACKGROUND The harm of smoking results mainly from long-term exposure to harmful and potentially harmful constituents (HPHCs) generated by tobacco combustion. Smoking cessation (SC) engenders favorable changes of clinical signs, pathomechanisms, and metabolic processes that together could reduce the harm of smoking-related diseases to a relative risk level approximating that of never-smokers over time. In most SC studies, the main focus is on the quitting rate of the SC program being tested. As there is limited information in the literature on short to multiple long-term functional or biological changes following SC, more data on short to mid-term favorable impacts of SC are needed. OBJECTIVE The overall aim of the study was to assess the reversibility of the harm related to smoking over 1 year of continuous smoking abstinence (SA). This has been verified by assessing a set of biomarkers of exposure to HPHCs and a set of biomarkers of effect indicative of multiple pathophysiological pathways underlying the development of smoking-related diseases. METHODS This multiregional (United States, Japan, and Europe), multicenter (42 sites) cohort study consisting of a 1-year SA period in an ambulatory setting was conducted from May 2015 to May 2017. A total of 1184 male and female adult healthy smokers, willing to quit smoking, were enrolled in the study. Nicotine replacement therapy (NRT) was provided for up to 3 months upon the subject’s request. SC counseling and behavioral support were continuously provided. Biomarkers of exposure to HPHCs and biomarkers of effect were assessed in urine and blood at baseline, Month 3, Month 6, and Month 12. Cardiovascular biomarkers of effect included parameters reflecting inflammation (white blood cell), lipid metabolism (high-density lipoprotein cholesterol), endothelial function (soluble intercellular adhesion molecule-1), platelet function (11-dehydrothromboxane B2), oxidative stress (8-epi-prostaglandin F2 alpha), and carbon monoxide exposure (carboxyhemoglobin). Respiratory biomarkers of effect included lung function parameters and cough symptoms. The biomarkers of effect to evaluate genotoxicity (total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) and xenobiotic metabolism (cytochrome P450 2A6 activity) were also assessed. Continuous SA was verified at each visit following the actual quit date using self-reporting and chemical verification. Safety assessments included adverse events and serious adverse events, body weight, vital signs, spirometry, electrocardiogram, clinical chemistry, hematology and urine analysis safety panel, physical examination, and concomitant medications. RESULTS In total, 1184 subjects (50.1% male) were enrolled; 30% of them quit smoking successfully for 1 year. Data analyses of the study results are ongoing and will be published after study completion. CONCLUSIONS This study provides insights into biological and functional changes and health effects, after continuous SA over 1 year. Study results will be instrumental in assessing novel alternative products to cigarettes considered for tobacco harm reduction strategies. CLINICALTRIAL ClinicalTrials.gov NCT02432729; http://clinicaltrials.gov/ct2/show/NCT02432729 (Archived by WebCite at http://www.webcitation.org/78QxovZrr) INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12138

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Adducts as Biomarkers of Effect of DNA-Reactive Carcinogens

Toxicological Sciences ◽

10.1093/toxsci/kfy161 ◽

2018 ◽

Vol 165 (1) ◽

pp. 5-5 ◽

Cited By ~ 1

Author(s):

Tetyana Kobets ◽

Gary M Williams

Keyword(s):

Biomarkers Of Effect

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Predicting Human Health Effects from Environmental Exposures: Applying Translatable and Accessible Biomarkers of Effect

10.17226/25962 ◽

2020 ◽

Author(s):

◽

Keyword(s):

Human Health ◽

Health Effects ◽

Environmental Exposures ◽

Human Health Effects ◽

Biomarkers Of Effect

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Medical and preventive technologies for risk management of health problems associated with exposure to environmental factors

Hygiene and Sanitation ◽

10.18821/0016-9900-2016-95-1-17-22 ◽

2019 ◽

Vol 95 (1) ◽

pp. 17-22 ◽

Cited By ~ 1

Author(s):

N. V. Zaytseva ◽

Olga Y. Ustinova ◽

A. S. Sboev

Keyword(s):

Risk Management ◽

Environmental Factors ◽

Preventive Measures ◽

Target Groups ◽

Treatment And Prevention ◽

Methodological Approaches ◽

Biomarkers Of Effect ◽

Diagnosis Of Diseases ◽

Research Analysis

In the article there are presented the methodological approaches to the diagnosis, treatment and prevention of diseases associated with the exposure to environmental factors, based on the principles of risk assessment of existing risk factors, confirmed exposure, identification of biomarkers of effect with the use of cellular-molecular, proteomic and nanotechnology, the results of clinical and functional research, analysis of the system relationships, exposure markers with markers for the negative response. Sanitary-hygienic, epidemiological, clinical, functional and laboratory criteria underlying the proposed classification of specialized medical preventive technologies for risk management, allow to make a differential diagnosis of diseases associated with the exposure to environmental factors according to their severity and stage of clinical manifestation, identify target groups ofpopulation to provide them specialized treatment and preventive care, determine the volume, direction, content and form of implementation of curative and preventive measures.

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Neuroantibody Biomarkers: Links and Challenges in Environmental Neurodegeneration and Autoimmunity

Autoimmune Diseases ◽

10.1155/2014/340875 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Hassan A. N. El-Fawal

Keyword(s):

Immune Response ◽

Nervous System ◽

Autoimmune Diseases ◽

High Throughput ◽

Humoral Immunity ◽

Therapeutic Efficacy ◽

Environmental Chemicals ◽

Specific Proteins ◽

Predicting Outcome ◽

Biomarkers Of Effect

The majority of neurodegenerative (ND) and autoimmune diseases (AID) remain idiopathic. The contribution of environmental chemicals to the development of these disorders has become of great interest in recent years. A convergence of mechanism between of ND and AID development has also emerged. In the case of ND, including neurotoxicity, the focus of this review, work over the last two decade in the realm of biomarker development, indicates that the immune response provides a venue whereby humoral immunity, in the form of autoantibodies to nervous system specific proteins, or neuroantibodies (NAb), may provide, once validated, a sensitive high throughput surrogate biomarker of effect with the potential of predicting outcome in absence of overt neurotoxicity/neurodegeneration. In addition, NAb may prove to be a contributor to the progression of the nervous system pathology, as well as biomarker of stage and therapeutic efficacy. There is a compelling need for biomarkers of effect in light of the introduction of new chemicals, such as nanoengineered material, where potential neurotoxicity remains to be defined. Furthermore, the convergence of mechanisms associated with ND and AID draws attention to the neglected arena of angiogenesis in defining the link between environment, ND, and AID.

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