Biomarkers in Toxicology

Preface
Series Preface
Contents
About the Editors
Contributors
Part I: Single Components
1 Soluble Guanylyl Cyclase Alpha1 Subunit as a Biomarker of Toxicity: Applications to Investigate Endocrine-Disrupting Chemica...
Introduction
Endocrine-Disruptor Compounds (EDCs)
Estrogens
Xenoestrogens
Current Screening Methods
Estrogen Receptor Binding Assay Using Rat Uterine Cytosol (ER-RUC)
Estrogen Receptor Transcriptional Activation
Steroidogenesis (Human Cell Line: H295R)
Rat Uterotrophic Assay
Rat Female Pubertal Assay
Fish Short-Term Reproduction Assay with Fathead Minnow (Pimephales promelas)
Soluble Guanylyl Cyclase
Estrogen and Soluble Guanylyl Cyclase
sGCα1 Subunit as a Biomarker of Exposure
Applications to Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of Endocrine-Disrupting Chemicals
Summary Points
Cross-References
References
2 Serum Paraoxonase 1 as a Biomarker in Toxicology
Introduction
Biochemical Properties and Gene Structure of Paraoxonase 1
Applications to Prognosis, Other Diseases, or Conditions
Organophosphate Exposure
Lipid Peroxidation
Liver Toxicity
Key Facts of Cirrhosis
Key Facts of Coronary Heart Disease (CHD)
Mini-dictionary of Terms
Summary Points
References
3 Erythrocyte Acetylcholinesterase as a Biomarker of Environmental Lead Exposure
Introduction
Chemistry, Forms, and Properties of Lead
Sources and Routes of Environmental Lead Exposure
Toxicokinetics of Lead
Absorption, Distribution, and Elimination of Lead
Toxicodynamics of Lead
Lead and Hematological Toxicity
Lead and Renal Toxicity
Lead and Cardiovascular Disease
Lead and Reproductive Toxicity
Lead and Bone Metabolism
Lead and Neurotoxicity
Cholinergic System
Acetylcholinesterase
Extraction and Purification of Erythrocyte Acetylcholinesterase
Erythrocyte Acetylcholinesterase in Biological Monitoring of Environmental Lead Exposure
Blood Lead Level Versus Erythrocyte Acetylcholinesterase in Lead-Induced Neurotoxicity
The Possible Mechanisms Surrounding the Interference of Lead with Erythrocyte Acetylcholine Activity
Application of Erythrocyte Acetylcholinesterase to Prognosis
Application of Erythrocyte Acetylcholinesterase to Other Conditions
Mini-Dictionary of Terms
Key Facts of Environmental Lead Exposure
Key Facts of Erythrocyte Acetylcholinesterase as a Biomarker of Environmental Lead Exposure
Summary Points
Cross-References
References
4 Fortilin as a Biomarker in Toxicity
Introduction
Fortilin Characterization
Fortilin Functions
Fortilin Roles in Cell Growth and Organ Development Process
Regulation of Protein Synthesis and Degradation
Biological Stress Reactions and Autophagy
Fortilin-ion Relationship
Fortilin and Sodium-Potassium ATPase
Fortilin and Calcium Ion
Fortilin´s Role in Apoptosis
Fortilin and p53-Independent Antiapoptosis
Fortilin and p53-Dependent Antiapoptosis
Fortilin as a Biomarker of Toxicity
Fortilin Investigation Methods
Northern, Southern, and Western Blot
Immunocytochemistry and Immunohistochemistry
Yeast Two-Hybrid Assay (Y2H)
Enzyme-Linked Immunosorbent Assay (ELISA)
Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Analysis
Recommendations
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of Fortilin and Fortilin Recombinant
Summary Points
References
5 Antibodies as Biomarkers: Effect of Microcystin Exposure
Introduction: Cyanobacteria, Their Toxins, and Health Risk
Microcystins: Structure and Toxicity Mechanisms
Chemical Structure
Molecular Mechanisms of Toxicity
Alterations of Cell Cycle
Toxicity on Organs
In Vivo Studies
In Vitro Studies
Biomarkers
Definition and Applications
Biomarkers of Microcystin Exposure
Antibodies as Biomarkers
Isotype Switch of Antibodies
Antibodies Against Microcystins
Applications to Prognosis
Mini-dictionary of Terms
Key Facts of Antibodies as Biomarkers: Effect of Microcystin Exposure
Key Facts of Cyanobacterial Blooms
Key Facts of Microcystins
Key Facts of Human Intoxications with Microcystins
Summary Points
Cross-References
References
6 Gamma-H2AX Expression as a Biomarker of Carcinogenesis: Applications to Toxicology
Introduction
Histone H2AX
Phosphorylation of H2AX (γH2AX)
Functions of γH2AX
Methods of γH2AX Detection
The Relationship Between γH2AX Formation and Carcinogens
Radiation
Oxidative Stress
Chemicals
γH2AX Formation as Genotoxic Biomarker in In Vitro Studies
γH2AX Formation as Biomarker of Carcinogen in In Vivo Studies
γH2AX Formation as Biomarker in Clinical Studies
γH2AX as a Prognostic Marker in Several Cancer Types
Conclusion
Mini-dictionary of Terms
Key Facts of Genotoxicity
Summary Points
References
7 The Carcinogen Glycidol and Use of N-(2,3-Dihydroxypropyl)-valine in Hemoglobin as a Biomarker of Exposure
Introduction
Occurrence and Toxicological Relevance of Glycidol
Human Exposure and Aspects of Hazard Characterization
Exposure Assessment of Glycidol
Biomarkers of Glycidol Exposure: Methodological Considerations
Biomarkers of Short- and Medium-Term Exposure
Edman Degradation and Mass Spectrometric Quantification of DHP-Val in Hb
Applications of DHP-Val as Biomarker of Glycidol Exposure
DHP-Val in Blood Samples from Rats and Humans
DHP-Val in Cord and Maternal Blood: Prenatal Exposure to Glycidol
Estimation of External Glycidol Exposure Using DHP-Val (Reverse Dosimetry)
Important Considerations for the Application of DHP-Val as Biomarker of Glycidol Exposure
Unknown Exposure Sources of Glycidol
Biomarker Specificity: Other Xenobiotic Precursors of DHP-Val?
DHP-Val from Endogenous Exposure to Glycidol or Other Reactants?
Mini Dictionary
Key Facts of Valine Adducts in Hb
Summary
References
8 Biomarkers of Antibiotic Toxicity: A Focus on Metronidazole
Introduction
Overview of Metronidazole
Mode of Action
Pharmacokinetics and Toxicity
Biomarkers of Antibiotic-Induced Toxicity
Biomarkers of Nephrotoxicity
Hepatotoxicity Biomarkers
Neurotoxicity Biomarkers
Genotoxicity Biomarkers
Application to Prognosis
Mini-Dictionary of Terms
Key Facts of Antibiotic-Induced Toxicity
Summary Points
Conclusion
Cross-References
References
Part II: Panels and Arrays
9 Pro-inflammatory Markers of Environmental Toxicants
Introduction
Polycyclic Aromatic Hydrocarbons (PAHs): Toxic Effects and Organ Damage
Effects of PAHs on Blood Biomarkers
The Effect of Inflammatory Biomarkers
Effects of PAH on Oxidative Stress and Mitochondrial Damage
Natural Antioxidants as Remedy Against PAH Toxicity
Phellinus torulosus as a Prophylactic Against DMBA Hepatotoxicity
P. torulosus Effects on TSPO Binding Potential
Studies About the Hepatoprotective Effects of Phellinus spp.
Applications to Prognosis, Other Diseases, or Conditions
Mini-dictionary of Terms
Key Facts of PAH-Derived Inflammation
Summary Points
References
10 Oxidative Stress Biomarkers and Their Applications to Detect Excessive Fluorine
Introduction
Sources of Fluoride Intake and Distribution in the Body
Influence of Fluorides on Organs and Systems
Effects on the Skeletal System and Teeth
Nervous System
Blood and Cardiovascular System
Gastrointestinal System
Urinary System
Respiratory System
Reproductive System
Endocrine System
Immune System
Skin
Oxidative Stress Biomarkers and Applications to Detect Excessive Fluorine
Biomarkers of Cell Redox Status
Transcription and Translation Processes
Biomarkers of Cell Membrane Permeability
Biomarkers of Intracellular Signaling Pathways
Biomarkers of Programmed Cell Death (Apoptosis)
Alterations in Cell Metabolism
Applications to Prognosis
Mini-dictionary of Terms
Key Facts of Fluorosis
Summary Points
Cross-References
References
11 Biomarkers of Alcohol Toxicity
Introduction
Alcohol as a Silent Universal Killer
Direct and Indirect Markers of Alcohol Use
Clinical Methods
Instrumental Methods
Classification of Biological Markers
Biochemical Methods
Immunochemistry Tests
Alcoholic Cardiomyopathy
Conclusions
Prospects for Further Research
Applications to Prognosis
Mini-dictionary of Terms
Key Facts About Alcohol
Summary Points
References
12 Biomarkers of Liver Injury due to Toxic Agents: Progress, Current Applications, and Emerging Directions
Introduction
Current Liver Injury Biomarkers
Limitations of the Current Biomarkers
Emerging Biomarkers of Etiology and Exposure
Emerging Predictive Biomarkers
Emerging Prognostic Biomarkers
Emerging Biomarkers with Greater Specificity
Mechanistic Biomarkers
Summary and Conclusions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of Acetaminophen
Key Facts of Acute Liver Injury
Key Facts of Acute Liver Failure
Key Facts of Drug-Induced Liver Injury
Key Facts of Pyrrolizidine Alkaloids
Summary Points
Cross-References
References
13 Biomarkers for Assessing Mycotoxin Exposure and Health Effects
Introduction
Regulations for Mycotoxins
Biomarkers of Exposure to Mycotoxins
Biomarkers of Aflatoxin Exposure
Biomarkers of Ochratoxin A Exposure
Biomarkers of Fumonisin Exposure
Biomarkers of Deoxynivalenol Exposure
Biomarkers of Zearalenone Exposure
Biomarkers of Mycotoxins Health Effects
Aflatoxins
Ochratoxin A
Deoxynivalenol
Fumonisins
Zearalenone
Concluding Remarks
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of Mycotoxin Biomarkers
Summary Points
Cross-References
References
14 Metabolomics Profiling of Di-(2-propylheptyl) Phthalate (DPHP) Biotransformation Products as Exposure Markers: Analytical S...
Introduction
DPHP Exposure Marker Discovery
Workflow of DPHP Exposure Marker Discovery
Sample Preparation and LC-MS Analysis
MS Data Processing Approaches
Dose-Response Verification
Chemical Structure Identification of DPHP Exposure Markers
Applications of DPHP Exposure Markers in Biospecimens
DPHP Exposure Markers in the Human Urine Sample
DPHP Exposure Markers in Hair Samples
Mini-dictionary of Terms
Key Facts of DPHP Exposure Markers
Summary Points
References
15 Biomarkers of Neurotoxicity
Introduction
Biomarkers of Oxidative Stress
Oxidative Stress: Definition, Causes, and Effects
Biomarkers
Products of Lipid Peroxidation
F2-Isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NeuroPs)
Isofurans (IsoFs) and neurofurans (NeuroFs)
Malondialdehyde (MDA)
4-Hydroxy-2-nonenal (4-HNE)
Products of Nucleic Acid Oxidation
8-Hydroxydeoxyguanosine (7,8-dihydro-8-oxodeoksyguanosine, 8-OHdG) and 8-hydroxyguanosine (7,8-dihydro-8-oxoguanosine, 8-OHG)
Other Products of Oxidation
Protein Carbonyl and Protein Nitration
Advanced Glycosylated End Products (AGEs)
Biomarkers of Antioxidant Defense
Neuroinflammation and Xenobiotics
The Role of Metabolic Disturbances in the Neurotoxic Effects of Xenobiotics
The Metabolic Disturbances Induced by Heavy Metals
Metabolic Disturbances in the Neurotoxic Effects of Pesticides
Sevoflurane: Disturbances of Glucose Metabolism and Iron Homeostasis
Excitotoxicity Induced by Xenobiotics
Types of Xenobiotic-Induced Nerve Cell Death
Conclusion
Mini-dictionary of Terms
Key Facts About Mechanisms of Neurotoxicity and Their Biomarkers
Summary Points
Cross-References
References
Part III: Genetic, Cellular, and Histological Variables
16 Genetic and Epigenetic Biomarkers Related to 2-Oxoglutarate/Fe(II)-Dependent Oxygenases and Implications for Disease and To...
Introduction
DNA Biomarkers
3-Methylcytosine (m3C) and 1-Methyladenosine (m1A)
1-Methylguanine (m1G) and 3-Methylthymine (m3T)
4-Methylcytosine (m4C) and 2-Methylguanine (m2G)
O6-Methylguanosine (O6mG)
5-Methylcytosine (m5C), 5-Hydroxymethylcytosine (hm5C), 5-Formylcytosine (f5C), and 5-Carboxylcytosine (ca5C)
N6-Methyladenine (m6A)
Thymine and β-D-Glucopyranosyloxymethyluracil (Base J)
Other Simple Alkylated DNA Biomarkers
Exocyclic DNA Biomarkers
RNA Biomarkers
3-Methylcytosine and 1-Methyladenine
3-Methyluracil (m3U)
1-Methylguanine and N2,N2-Dimethylguanine (m22G)
5-Methylcytosine, 5-Hydroxymethylcytosine, 5-Formylcytosine, 5-Hydroxymethyl-2′-O-Methylcytosine, and 5-Formyl-2′-O-Methylcyto...
N6-Methyladenine
5-Carboxymethyluridine (cm5U) and 5-Methoxycarbonylmethyluridine (mcm5U)
AlkB Family and TET/JBP Family Enzymes
Brief Summary of Spectroscopic and Computational Studies
Applications to Prognoses, Other Diseases, or Conditions
Conclusions and Perspectives
Mini-Dictionary of Terms
Key Facts of 2-Oxoglutarate/Fe(II)-Dependent Oxygenases
Summary Points
References
17 DNA Adducts as Biomarkers in Toxicology
Introduction
32P Postlabeling
Antibody-Based Methods
MS Methods
Accelerator MS (AMS)
Gas Chromatography-MS (GC-MS)
LC-MS/MS
DNA Adducts as Biomarkers for Alcohol Consumption
Acetaldehyde DNA Adducts
Crotonaldehyde DNA Adducts
Radiation-Induced DNA Adducts
UV-Induced DNA Adducts
IR-Induced DNA Adducts
Heterocyclic Aromatic Amine (HAA) DNA Adducts
2-Amino-3,8-Dimethylimidazo[4,5-f] Quinoxaline (MeIQx)
2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine (PhIP)
Aromatic Amine DNA Adducts
4-Aminobiphenyl (4-ABP)
Aflatoxin B (AFB) DNA Adducts
Aristolochic Acid DNA Adducts
N-nitroso Compound (NOCs) DNA Adducts
Aromatic Hydrocarbon DNA Adducts
Benzene
Benzo[α]pyrene (BaP)
Nitrosamines
Carbonyl Adducts
Acrolein
Methylglyoxal (MG)
Formaldehyde
Pesticides
Butadiene
Chemotherapy-Induced DNA Adducts
Platinum (Pt)-Based Chemotherapy Drugs
Temozolomide
Mitomycin C
Tamoxifen
Applications to Prognosis
Key Facts of DNA Biomarkers in Toxicology
Mini-Dictionary of Terms
Summary Points
Cross-References
References
18 DNA Methylation as a Biomarker and Application to Aluminum: ADRB2 5′-Untranslated Region (5′-UTR) Methylation Level
Introduction
Bronchial Asthma
The β-2 Adrenergic Receptor (ADRB2)
Aluminum
Aluminum and ADRB2 5′-Untranslated Region (5′-UTR) Methylation Level
Bronchial Asthma and Epigenetic Events
Potential Applications to Prognosis
Mini-dictionary of Terms
Key Facts
Summary Points
References
19 Autophagy as a Biomarker of Cytotoxicity
Introduction
Autophagy and Its Membrane Biogenesis
Selective Autophagy, LC3-Associated Phagocytosis (LAP), and Amphisomes
Measurement of Autophagy Flux
Cytotoxic and Cytoprotective Roles of Autophagy
Biomarkers in Autophagy-Induced Cytotoxicity
Conclusions and Implications for Autophagy Biomarkers of Cytotoxicity
Applications for Prognosis of Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of Autophagy Membrane Biogenesis
Summary Points
References
20 Erythrocyte Glutathione Transferase P1-1 as a Biomarker in Environmental Toxicology: A New Narrative
Introduction
GSTs and Toxin Exposure
The Peculiar Molecular Properties of GSTP1-1
Activity Detection of GSTP1-1 in Biological Samples: Critical Points
GSTP1-1 Polymorphism
GSTP1-1: An Enzyme Dedicated to Biomedical Applications
Hyper-Expression of GSTP1-1
Tissue Distribution of GSTP1-1 in Humans
GSTP1-1 in Human Pathologies
e-GST as a Long-Term as Well as a Short-Term Biomarker of Blood Toxicity
Human e-GST as Biomarker in Environmental Toxicology
Mammalian e-GST as Biomarker in Environmental Toxicology
e-GST in Fish Erythrocytes
e-GST as Biomarker in Environmental Toxicology in Other Animal Species
Future Perspective and Clinical Applications
Applications to Prognosis and Diseases
Mini-dictionary
Key Facts of Glutathione Transferase
Summary Points
References
21 Extracellular MicroRNAs as Putative Biomarkers of Air Pollution Exposure
Introduction
Methods of MiRNA Measurement
Sample Types
Sample Processing
Sampling MiRNAs from Different Biological Contexts
Expression Analysis
Effects of Air Pollution on MiRNA Expression
Effects of PM Exposure
Effects of Diesel Exhaust Exposure
Effects of Ozone Exposure
Effects of NOx Exposure
Effects of SOx Exposure
Effects of Wildfire Smoke Exposure
Air-Pollution-Induced Effects Through MiRNA Regulation
Future Perspectives
Application
Limitation
Conclusions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of MicroRNA
Summary Points
Cross-References
References
22 Endothelial Extracellular Vesicles as Biomarkers of Toxic Molecules
Introduction
EVs´ Classification
Isolation of Endothelial EVs
Ultracentrifugation-Based Techniques
Size Exclusion Chromatography (SEC)
Ultrafiltration
Polymer-Based Precipitation
Immunoaffinity-Based Techniques
Analysis of Endothelial EVs
Electron Microscopy
Atomic Force Microscopy (AFM)
Nanoparticle Tracking Analysis (NTA)
Dynamic Light Scattering (DLS)
Flow Cytometry
Proteomics
Transcriptome
qRT-PCR
Next-Generation Sequencing (NGS/RNA-seq)
Microarrays
Other Techniques
Endothelial EVs in Cardiovascular Diseases and Kidney Diseases
EVs and Cardiovascular Diseases
EVs and Kidney Diseases
Final Considerations
Applications to Prognosis
Mini-Dictionary of Terms
Key Facts of Cardiovascular Diseases
Key Facts of Chronic Kidney Disease
Summary Points
Cross-References
References
Part IV: Functional and Physiological Variables and Platforms
23 Biomarkers of Lead Exposure: Platforms and Analysis
Introduction
Biological Matrices and Lead Exposure Biomarkers
Teeth
Bone
Nail
Blood
Plasma
Urine
Saliva
Hair
Elemental Analysis
Sample Preparation
Instrumental Analysis
Applications to Prognosis, Other Diseases, or Conditions
Dictionary of Terms
Summary Points
References
24 Murine Embryonic Stem Cells as Platform for Toxicity Studies: Use of Human Survivin Promoter with Green Fluorescent Protein...
Introduction
Limitations of Animal Models
In Vitro Assays for Developmental Toxicity Assessment
MM Test
WEC Test
Zebrafish Embryo Assay
Frog Embryo Teratogenesis Assay
Embryonic Stem Cell Test (EST)
mESC-Based Reporter Gene Assays
EST with Luciferase Reporter Gene
EST with GFP Reporter Gene
mESCs for HTS of Embryotoxic Chemicals
Survivin as a Biomarker for Apoptosis Inhibition and Embryotoxicity Screening
Other Potential Biomarkers for Embryotoxicity Screening
Conclusion
Summary Points
References
25 LC-MS-Based Metabolomics in the Identification of Biomarkers Pertaining to Drug Toxicity: A New Narrative
Introduction
Metabolomics
Analytical Platforms in Metabolomics
NMR-Based Metabolomics
MS-Based Metabolomics
Types of Metabolomics
LC-MS-Based Metabolomics: Workflow and Experimental Design for Drug Toxicity
Experiment Design
Sample Collection and Preparation
Data Acquisition and Analysis
Data Explanation and Biological Question Addressing
Applications of LC-MS-Based Metabolomics for the Study of Drug Toxicity
The Roles of Metabolomics in Drug Toxicity
Screening Drug Metabolites
Identifying Biomarker and Mechanisms of Drug Toxicity
Drug-Induced Hepatotoxicity
Drug-Induced Toxicity in Other Organs
Discussion and Future Directions of Biomarker Identification
Applications to Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of ``LC-MS-Based Metabolomics in the Identification of Biomarkers Pertaining to Drug Toxicity: A New Narrative´´
Summary Points
Cross-References
References
26 Bovine Whole Blood Cells as a Biomarker Platform for Biological Toxicology: A Focus on Thiacloprid
Introduction
Neonicotinoid Insecticides
Thiacloprid
Genotoxicity of Thiacloprid
Genotoxicity of Other Neonicotinoids
Bovine Cell Cultures
Applications to Prognosis, Other Diseases, or Conditions
Mini-dictionary
Key Facts
Summary Points
Cross-References
References
27 Blood-Brain Barrier Function as a Biomarker in Toxicology: Impact of Environmental Toxicants
Introduction
Overview of the Blood-Brain Barrier
Blood-Brain Barrier Dysfunction as a Biomarker of Toxicity and Disease
Polycyclic Aromatic Hydrocarbons
Dioxins
Perfluoroalkyl Substances
Heavy Metals
Airborne Toxicants and Pollutants
Approaches to Studying BBB Permeability
Postmortem and In Situ Assessment
In Vivo Neuroimaging
Ex Vivo Resected Blood Vessel Assay
In Vitro Platforms
Electrical Cell-Substrate Impedance Sensing (ECIS)
Transwell Scaffold Model
Organoids
Chips/Microfluidics
Other Platforms
Conclusion
Applications to Prognosis and Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Blood-Brain Barrier Function as a Biomarker Platform in Toxicology: Impact of Toxicants
Summary Points
Cross-References
References
28 Anogenital Distance: Features, Measures, and Uses as a Biomarker for Toxicity In Utero
Introduction
Sex Determination and the Early Stages of Sexual Development
Androgen-Dependent Masculinization
Why Measure AGD
AGD in Rodent Toxicity Studies
AGD in Human Epidemiological Studies
How AGD Is Measured
AGD Measurements in Rodents
AGD Measurement in Humans
Final Remarks
Application to Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of Androgen-Dependent Sexual Development
Summary Points
References
29 Micronucleus Assay in Lymphocytes for Human Biomonitoring and Clinical Studies
Introduction
Occupational and Environmental Monitoring
Micronuclei in Lymphocytes in the Clinical Settings
Applications to Prognosis
Key Facts of Micronucleus Assay in Lymphocytes for Human Biomonitoring and Clinical Studies
Mini Dictionary of Terms
Summary Points
References
30 Salivary Biomarkers in Toxicology: An Update Narrative
Introduction
General Aspects
Biomarkers and Classes of Biomarkers
Saliva as a Biological Fluid for the Detection of Markers and Biomarkers for Diagnosis and Toxicology Assessment
Toxicology and Biomarkers
Biomarkers of Exposure
Biomarkers of Response or Toxic Effect
Biomarkers of Susceptibility
Analytical Methods
Separation Methods
Electrochemical Methods
Spectral Methods
Chemometrics
Toxicity and Sources of Toxicity
Pollutant-Induced Toxicity
Toxicity Induced by Local Pathologies
Toxicity Induced by Drug Screening
Toxicity Induced by Tobacco and Drugs of Abuse
Influence of Toxic Factors on Biomarker Levels
Conclusions
Mini-Dictionary of Terms
Key Facts of Salivary Biomarkers in Toxicology
Summary Points
References
Part V: Biomarkers in Specific Conditions or Scenarios
31 Doxorubicin Cardiotoxicity: Preclinical and Clinical Circulating Protein Markers
Introduction
Cardiotoxicity as a Serious Adverse Effect of Doxorubicin
Proposed Mechanisms of Cardiotoxicity
Potential Risk Factors Associated with Cardiotoxicity
Technical Barriers for Predicting Early Signs of Cardiac Dysfunction Induced by Doxorubicin
Circulating Protein Markers of Doxorubicin-Induced Cardiotoxicity
Preclinical Markers of Cardiotoxicity
Glycogen Phosphorylase Brain/Heart Isoform
Neurogenic Locus Notch Homolog Protein 1 and von Willebrand Factor
Clinical Markers of Cardiotoxicity
Traditional Cardiac Disease Markers
Promising Markers of Cardiotoxicity
Applications to Prognosis
Mini-dictionary of Terms
Key Facts of Doxorubicin Cardiotoxicity
Summary Points
References
32 Biomarkers of Sulfur Mustard (Mustard Gas) in Urine
Introduction
History
Toxicokinetics of Sulfur Mustard
Mechanism of Action
Clinical Toxicology of SM Poisoning
Medical Management of SM Poisoning
Laboratory Diagnosis of SM Poisoning through Urinary Metabolites
Applications to Prognosis
Mini-Dictionary of Terms
Key Facts of Biomarkers of Sulfur Mustard (Mustard Gas) in Urine
Summary Points
References
33 Biomarkers of Cardiopulmonary Injury and Impact of Bromine Toxicity
Introduction
Mechanisms, Presentation, and Biomarkers of Respiratory Bromine Toxicity
Mechanisms, Presentation, and Biomarkers of Cardiac Bromine Toxicity
Mechanisms, Presentation, and Biomarkers of Bromine Toxicity on External Tissues
Systemic Mechanisms, Presentation, and Biomarkers of Bromine Toxicity
Conclusions
Mini-Dictionary of Terms
Key Facts on Bromine
Summary Points
References
34 Biomarkers of PM2.5 Exposure: Use of Metabolomics as a Platform
Introduction
Untargeted Metabolomics
Retrieving Relevant Research Studies
Studies of Human Blood
Studies of Human Urine
Studies of Animal Blood
Studies of Animal Urine
Applications to Prognosis, Other Diseases, or Conditions
Mini-dictionary of Terms (5-15 Terms)
Key Facts of Biomarkers of PM2.5 Exposure: Use of Metabolomics as a Platform
Summary Points
References
35 Sunscreens: Toxic Effects as Determined by Biomarkers
Introduction
Sunscreen-Induced Skin Toxicity
Organic Sunscreen Filter Ingredients and Their Toxicity
Inorganic Sunscreen Filter Ingredients and Their Toxicity
Biomarkers in Sunscreen-Induced Skin Toxicity
Sunscreen Filters Tests as Biomarkers
Oxidative Stress Biomarkers and Their Role in Sunscreen-Induced Skin Toxicity
Oxidative Stress Biomarkers and Apoptosis
Pro-inflammatory Markers and Their Role in Sunscreen-Induced Toxicity
Inflammation Identifiers as Biomarkers
Application to Prognosis
Mini-Dictionary
Key Facts of Sunscreens: Toxic Effect as Determined by Biomarkers
Summary Points
References
36 Drug-Induced Nephrotoxicity and Use of Biomarkers
Introduction
Mechanisms of Drug-Induced Nephrotoxicity
Changes in Glomerular Hemodynamics
Tubular Cell Toxicity
Inflammation
Crystal Nephropathy
Rhabdomyolysis
Thrombotic Microangiopathy
Nephrotoxicity Biomarkers
Conventional Biomarkers
Creatinine
Glomerular Filtration Rate (GFR)
Blood Urea Nitrogen (BUN)
Albuminuria/Proteinuria
Urine Sediment Microscopy
Novel Biomarkers
Neutrophil Gelatinase-Associated Lipocalin (NGAL)
Interleukins
Kidney Injury Molecule 1 (KIM 1)
Liver-Type Fatty Acid-Binding Protein (L-FABP)
Calprotectin
Brain Natriuretic Peptide (BNP)
Soluble ST2
Galectin-3
IGFBP7 x TIMP2
Urinary Angiotensinogen (UAG)
Urinary MicroRNA
β2-Microglobulin (β2M)
Cystatin C (Cys C)
Clusterin
Collagen
Osteopontin
Symptoms of Nephrotoxicity
Diagnostic Tests for Nephrotoxicity
Disorders Related to Nephrotoxicity
Glomerulonephritis
Interference in Intra-renal Renin-Angiotensin System
Renal Tubule Acidosis
Chronic Kidney Disease (CKD)
Preventing Drug-Induced Impairment
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of Drug-Induced Nephrotoxicity and Use of Biomarkers
Summary Points
Cross-References
References
37 Biomarkers of Tobacco Use: Relevance to Tobacco Harm Reduction
Introduction
Harm Reduction
Alternative Nicotine-Containing Products
Cigarette Smoking and Disease
Biomarkers Related to Tobacco Use
Biomarkers of Exposure and Tobacco Use
Changes in Biomarkers of Exposure Accompanying Changes in Tobacco Use
Biomarkers of Potential Harm
Changes in Biomarkers of Potential Harm Accompanying Changes in Tobacco Use
Conclusions
Applications to Prognosis
Applications to Other Diseases or Conditions
Mini-Dictionary of Terms
Key Facts of Cigarette Smoking and Biomarkers of Exposure and Potential Harm
Summary Points
References
38 Bleaching Agents as Toxic Compounds and Biomarkers of Damage
Introduction
Chemical Bleaching Agents
Hydrogen Peroxide
Carbamide Peroxide
Chemical Mechanism of Tooth Bleaching
Toxicity of Tooth Bleaching
Natural Alternative Bleaching Agents
Papain, Bromelain, and Ficin
Chlorine Dioxide
Sodium Chloride and Sodium Bicarbonate
Natural Extract Combined with Hydrogen Peroxide
Nanoparticle-Added Bleaching Agents
Polymeric Nanoparticle
Nitrogen-Doped Titanium Dioxide
Nano-bioactive Material
Chitosan
Ozone
Low-Intensity Laser
Applications to Prognosis
Damage Biomarkers
Electron Paramagnetic Resonance
Determination of Oxidative Stress Markers
Determination of Lipid Peroxidation Products
Determination of Protein Damage (Hyaluronic Acid and Proteoglycans)
DNA Damage
Measurement of the Antioxidant Defense System
Antioxidant Enzymes
Determination of Total Antioxidant Activity
Measurement of Low-Molecular-Weight Antioxidants
Measurement of Enzyme Cofactors
Mini-dictionary of Terms
Key Facts of Bleaching Agents as Toxic Compounds and Biomarkers of Damage
Summary Points
References
39 Endocrine Disruptors and Markers of Anthropogenic Activity: A Risk for Water Supply and Health
Introduction
Effects of Endocrine Disruptors on Public Health and the Environment
Examples of Endocrine Disruptors and Markers of Anthropogenic Activities
Extraction Methods for Endocrine-Disrupting Micropollutants
Endocrine Disruptor Analysis
Applications to Prognosis
Mini-dictionary of Terms
Key Facts of Endocrine Disruptors and Markers of Anthropogenic Activity: A Risk for Water Supply and Health
Summary Points
Cross-References
References
40 Biomarkers in the Biomonitoring of Fluoride Toxicity: An Overview
Introduction
A Brief History of Fluoride
Sources of Fluoride Exposure
Fluoride and Diseases
Biomarkers: A New Era for Diagnosis?
Biomarkers and Fluoride: What´s in the Literature?
Conclusion
Mini-Dictionary of Terms
Key Facts
Summary Points
Cross-References
References
41 New Approaches to Evaluate the Cytotoxic Potential of Leishmanicidal Drugs Using Human Peripheral Blood
Leishmaniasis: Neglected Tropical Diseases Are Still Spreading Around the World
Leishmaniasis Treatment
Leishmaniasis: The Immune Response for Parasite Control and New Drug Targets
New Drugs Are Needed!
Challenges in the Drug Discovery for New Leishmanicidal Drugs
A Quick Look at In Vitro Assays to Screen New Chemical Entities for Leishmania and Existent Preclinical Assays
Current Assays to Measure the Cytotoxicity of Chemical Entities
Proposal of Human Peripheral Leukocytes (HPL) of Whole Blood as a Model to Measure the Cytotoxicity of Leishmanicidal Drugs
Final Remarks
Applications to Other Disease
Mini-Dictionary of Terms
Key Facts of the Human Whole Blood Model to Measure the Cytotoxicity of Leishmanicidal Drugs
Summary Points
References
42 Contrast-Induced Nephropathy (CIN) and Biomarkers
Introduction
Acute Kidney Injury
Contrast-Induced Nephropathy
Biomarkers
Functional Biomarkers
Creatinine
Cystatin C (Cys-C)
Microalbuminuria
β2-Microglobulin (β2M)
Structural Biomarkers
Neutrophil Gelatinase-Associated Lipocalin (NGAL)
N-Acetyl-b-D-Glucosamine (NAG)
Kidney Injury Marker 1 (KIM-1)
Interleukin 18 (IL-18)
Liver-Type Fatty-Acid-Binding Protein (L-FABP)
Midkine
Dickkopf-3 (DKK3)
Miscellaneous Biomarkers for CIN
Gamma-Glutamyl Transferase (GGT)
Homocysteine
Procalcitonin
Hepcidin
G1 Cell-Cycle Arrest Proteins
Semaphorin 3A
Fibroblast Growth Factor 23 (FGF23)
Growth Differentiation Factor 15 (GDF-15)
Uric Acid (UA)
Adiponectin
Glucose
Copeptin
Circulating microRNA (miRNA)
C-Reactive Protein (CRP)
Asymmetric Dimethylarginine (ADMA)
Applications to Prognosis
Applications to Other Diseases or Conditions
Conclusion
Mini-Dictionary of Terms
Key Facts of CIN
Summary Points for CIN
References
43 Lead and Aquatic Ecosystems, Biomarkers, and Implications for Humankind
Introduction
Sources of Lead Exposure
Lead as a Toxic Pollutant
Lead in Aquatic Environment
Uptake and Bioaccumulation of Lead
Absorption of Lead
Excretion of Lead
Mechanism of Lead Toxicity
Effects of Lead Toxicity on Aquatic Organisms
Impact of Lead Toxicity on Humankind
Hematopoietic System
Cardiovascular System
Renal System
Skeletal System
Nervous System
Respiratory System
Liver and Gastrointestinal Tract
Reproductive System
Applications to Prognosis and Other Diseases or Conditions
Mini-dictionary of Terms
Key Facts of Oxidative Stress
Key Facts of Atherosclerosis
Key Facts of Na+/K+ ATPase
Summary Points
Cross-References
References
44 Per- and Polyfluoroalkyl Substances (PFAS) and Their Toxicology as Evidenced Through Disease and Biomarkers
Key Facts of PFAS
Introduction
PFAS Types
Bioaccumulation
Environmental Distribution
Environmental Problems
Remediation
Molecular Initiating Events
Nuclear Receptors
Peroxisome Proliferator-Activated Receptors (PPARs)
Molecular Biomarkers
Health Effects
Metabolic / Hepatotoxicity
Immune
Developmental/Reproductive
Endocrine
Cardiovascular
Neurotoxicity
Cancer
Summary
Mini-Dictionary of Terms
Summary Points
References
45 The Complement System as a Biomarker of Environmental Pollutants as Toxic Agents: A Focus on Polybrominated Diphenyl Ethers...
Introduction
Polybrominated Diphenyl Ethers Poisoning Around the World
Polybrominated Diphenyl Ethers Group: Isomers and Congeners
Polybrominated Diphenyl Ethers in the Environmental and Human Health
Polybrominated Diphenyl Ethers in Immune System
Complement System
Effects of Polybrominated Diphenyl Ethers on the Complement System
Applications of Complement Components as Biomarkers of PBDEs Exposure
Mini-Dictionary of Terms
Key Facts of Environmental Pollutants
Summary Points
Cross-References
References
46 Biomarkers of the Toxic Effects of Chemotherapeutic Agents: A Focus on Antimalarials
Introduction
Antimalarial Drugs
Mode of Action and Metabolism of Antimalarial Drugs
Toxicity of Antimalarial Drug
Biomarkers of the Toxicity of Antimalarial Drugs
Cytochrome P450
Drug Transporter
P-Glycoprotein
Organic Anion Transporter 1B1
Glucose-6-Phosphate Dehydrogenase
Glutathione S-Transferase
Potential Applications to Prognosis, Other Diseases, or Conditions
Summary
Key Facts of Antimalarial Toxicity
Mini-Dictionary of Terms
References
Part VI: Biomarkers in Models and Modeling Toxicity
47 Linking Arsenic, DNA Methylation Biomarkers, and Transgenerational Neurotoxicity: Modeling in Zebrafish
Introduction
Transgenerational Epigenetic Inheritance
Role of Arsenic-Induced DNA Methylation in Neurotoxicity
Modeling Transgenerational Arsenic Neurotoxicity in Zebrafish
Affordable Methodologies for the Study of DNA Methylation in Zebrafish
Global DNA Methylation
Gene-Specific Methylation
Potential DNA Methylation Biomarkers for Transgenerational Neurotoxicity of Arsenic
Global DNA Methylation
Differentially Methylated Regions
Gene-Specific Methylation
The Brain-Derived Neurotrophic Factor (BDNF) and Tropomyosin-Related Receptor Kinase B (TrkB) Genes
The Myelin Basic Protein (MBP) Gene
The Reelin (RELN) Gene
The Protein Phosphatase 1 Gene
The Cystine/Glutamate Transporter (SLC7A11) Gene
Applications to Prognosis, Other Diseases, or Conditions
Mini-Dictionary of Terms
Key Facts of DNA Methylation by Arsenic Exposure
Summary Points (5-15)
Cross-References
References
48 Modeling with Biomarkers: Nitrosamines and Phytochemical Protection
Introduction
Nitrosamines
Chemical Structure
Sources
Cytotoxicity
Phytochemicals
Definition and Classification of Phytochemicals
Polyphenols
Terpenoids
Thiols
Medicinal Plants Role in Prevention of DEN-Induced Cytotoxicity
Capsicum Plant Species
Garcinia kola
Protium heptaphyllum
Cnidoscolus aconitifolius
Ipomoea batatas
Zingiber officinale
Litchi chinensis
Stephania tetrandra
Tripterygium wilfordii (Hook F)
Salvia miltiorrhiza
Polygonum cuspidatum, Morus alba, Vitis vinifera, and Red Wine
Rosmarinus officinalis
Ribes nigrum (Black Currant)
Pomegranate
Grapes, Berries, Peanuts, and Red Wine
Rice Bran
Garlic and Cinnamon Oils
Phoenix dactylifera L.
Curcuma longa
Conclusion
Summary Points
Cross-References
References
49 Different Mice Strains in Biomarker Responses to Toxic Agents: The Example of Acetaminophen
Introduction
Acetaminophen Epidemiology
Mechanisms of Acetaminophen Toxicity
Treatment for Acetaminophen Overdoses: Classic and New Approaches
Mice Models of Acetaminophen Toxicity
Routes of Inoculation of APAP
Different Mice Strains Responses to Acetaminophen
Applications and Importance of APAP Studies
Mini-Dictionary of Terms
Key Facts of Acetaminophen Toxicity
Abbreviations Such as APAP, AC, Acetaminop, Acetamin, or Acetam, May Be Written on the Label in Place of the Word Acetaminophen
Summary Points
References
Part VII: Resources
50 Recommended Resources for Biomarkers in Disease: Toxicology
Introduction
Resources
Other Resources
Summary Points
References
Index