دانلود کتاب Biomarkers in Toxicology (Biomarkers in Disease: Methods, Discoveries and Applications)

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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