Reactive Oxygen Species (ROS), Nanoparticles, and Endoplasmic Reticulum (ER) Stress-Induced Cell Death Mechanisms

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Reactive Oxygen Species (ROS), Nanoparticles, and Endoplasmic Reticulum (ER) Stress-Induced Cell Death Mechanisms
Copyright
Contents
About the author
Preface
Summary
Chapter 1: Pathophysiological, toxicological, and immunoregulatory roles of reactive oxygen and nitrogen species (RONS)
1.1. Oxidative and nitrative stress in toxicology and disease
1.2. Oxidative and nitrative stress: Role in the response to liver toxicants (Roberts)
1.2.1. Carcinogenesis and inflammation
1.2.2. Crosstalk with PPARα?
1.3. Characterization of oxidative stress using neuronal cell culture models (Smith)
1.4. Nitrative stress and glial-neuronal interactions in the pathogenesis of Parkinsons disease (Tjalkens and Stephen Safe)
1.4.1. Neuroinflammation and PD
1.4.2. Regulation of neuroinflammatory genes in astrocytes
1.4.3. Therapeutic strategies to interdict neuroinflammation
1.5. Oxidative and nitrative stress in multistage carcinogenesis (Robertson)
1.6. Role of peroxynitrite in the pathogenesis of doxorubicin-induced cardiotoxicity (Szabo)
1.6.1. Molecular mechanisms of peroxynitrite formation
1.7. Immunoregulatory role of ROS
1.8. Conclusions
References
Chapter 2: Biological mechanisms of reactive oxygen species (ROS)
2.1. Exogenous source of oxidants
2.1.1. Cigarette smoke
2.1.2. Ozone exposure
2.1.3. Hyperoxia
2.1.4. Ionizing radiation
2.1.5. Heavy metal ions
2.2. Endogenous sources of ROS and their regulation in inflammation
2.3. Mitochondria as main source of ROS in autophagy signaling
2.4. ROS and mitophagy
2.5. Production of ROS and their mechanisms of biological activities
2.6. Increased ROS production in photosynthesis during drought
2.7. ROS elimination
2.8. Types of reactive oxygen species
References
Chapter 3: Cellular signaling pathways with reactive oxygen species (ROS)
3.1. Oxidative stress and ROS
3.2. Sources of ROS
3.2.1. Endogenous sources and localization of ROS
3.2.1.1. Mitochondria
3.2.1.2. Endoplasmic reticulum
3.2.1.3. Soluble enzymes
3.2.1.4. Lipid metabolism
3.2.1.5. NADPH oxidase
3.2.2. Exogenous sources of ROS
3.2.3. The homeostasis of ROS
3.3. Oxidative stress in RA
3.4. Molecular targets of ROS
3.4.1. Protein tyrosine phosphatases and kinases
3.4.2. Lipid metabolism
3.4.3. Ca2+ signaling
3.4.4. Small GTPases
3.4.5. Serine/threonine kinases and phosphatases
3.5. Redox regulation of transcription factors
3.5.1. Nuclear factor κ-light-chain-enhancer of activated B cells
3.5.2. Activator protein-1
3.5.3. Other transcription factors
3.6. RA, pathogenesis, and therapy
3.7. Oxidative stress/ROS-associated consequences in RA
3.7.1. Lipid peroxidation
3.7.2. Effects on immunoglobulin advanced glycation end-products
3.7.3. Oxidative stress/ROS-mediated alteration of autoantigens
3.7.4. Genotoxic effects of oxidative stress
3.7.5. Oxidative stress and tissue injury
3.7.6. Cartilage/collagen effects
3.8. ROS-mediated pathways in cell death
3.8.1. Extrinsic pathways
3.8.2. Intrinsic pathways
3.9. ROS-mediated cellular signaling in RA
3.9.1. MAPK signaling pathway
3.9.2. PI3K-Akt signaling pathway
3.9.3. ROS and NF-κB signaling pathway
3.9.4. Oxidative stress/ROS as signaling in T-cell tolerance
3.10. The homeostasis of ROS
3.11. ROS and the NF-κB signaling pathway
3.12. ROS and MAPK signaling pathway
3.13. ROS and the keap1-Nrf2-ARE signaling pathway
3.14. ROS and the PI3K-Akt signaling pathway
3.15. Crosstalk between ROS and Ca2+
3.16. Reactive oxygen species and mitochondrial permeability transition pore
3.17. ROS and protein kinase
3.18. ROS and the ubiquitination/proteasome system
3.19. Lipid accumulation in oleaginous microorganisms under different types of stress
3.19.1. Nutrient limitation
3.19.2. Physical environmental stresses
3.19.3. Stress-induced strategies for generation and its potential role in lipid accumulation
3.19.4. Redox homeostasis and oxidative stress
3.19.5. Stress sensing and putative concomitant ROS generation
3.19.6. Transduction of intracellular ROS signals
3.19.7. Possible links between ROS and lipid accumulation
References
Chapter 4: Manganese as the essential element in oxidative stress and metabolic diseases
4.1. Effects of Mn on the role of reactive oxygen species
4.2. Physiological roles of Mn
4.3. Mn as metalloenzymes and as an enzyme activator
4.4. Mn stability and transport
4.5. Mn administration, distribution, and excretion
4.6. Brain Mn targets
4.7. Mn and metabolic syndrome
4.8. Mn and T2DM/insulin resistance
4.9. Mn and obesity
4.10. Mn and atherosclerosis
4.11. Mn and nonalcoholic fatty liver disease
4.12. Mn and autoxidation of catecholamines and other neurotransmitters
4.13. Mitochondria, the MPT, and apoptosis
4.14. Mn, ROS, the mitochondria, and apoptosis
4.15. A case for the use of mitochondrially targeted antioxidants
4.16. Conclusion
References
Further reading
Chapter 5: Affected energy metabolism is the primal cause of manganese toxicity
5.1. Affected energy metabolism
5.1.1. Gene expression profile under Mn stress
5.1.2. Mn-induced iron depletion blocks ISC and heme protein biogenesis
5.1.3. Mature ISC and heme protein deficiency affects energy metabolism
5.1.4. Reduced ETC function evokes ROS under Mn stress
5.1.5. Affected energy metabolism determines Mn toxicity
5.2. Mechanism of Mn-induced cellular toxicity
5.3. Polynitrogen Mn complexes
5.3.1. Cytotoxicity of Mn complexes 1 and 2
5.3.2. Effects of different concentrations of H2O2 on apoptosis of PC12 cells
5.3.3. Protection of preconditioning with Mn complexes against H2O2-induced death of neuronal cells
5.3.4. Time course analysis of intracellular ROS level changes
5.3.5. Effects of Mn complexes on the mRNA levels of HIF-1α and HIF target genes in cultured cells
5.3.6. Effects of Mn complexes on the protein levels of HIF-1α and HIF target genes in cultured cells
5.3.7. HIF-1α knockdown-induced apoptotic cell death under preconditioning with Mn complexes of neuronal cells
5.4. Neuroprotection-related signaling pathways of Mn complexes 1 and 2
5.5. Conclusion
References
Chapter 6: Heavy metals and free radical-induced cell death mechanisms
6.1. Heavy metal ions
6.2. Occurrence and recovery of heavy metals
6.3. Free radicals
6.3.1. Definition of free radicals
6.4. Heavy metals and their risky role on organisms of biological systems
6.5. Bioimportance of some heavy metals
6.6. Ecotoxicology and metabolism of heavy metals
6.7. Toxicity of xenobiotic metals (mercury, lead, cadmium, tin, and arsenic)
6.7.1. Mercury
6.7.2. Lead
6.7.3. Cadmium
6.7.4. Tin
6.7.5. Arsenic
References
Chapter 7: Cytotoxic mechanisms of xenobiotic heavy metals on oxidative stress
7.1. Effects of lead on oxidative stress
7.2. Effects of iron on oxidative stress
7.3. Effects of mercury on oxidative stress
7.4. Effects of copper on oxidative stress
7.5. Effects of cadmium and zinc on oxidative stress
7.6. Effects of arsenic on oxidative stress
7.7. Effects of chromium on oxidative stress
7.8. Effects of vanadium on oxidative stress
7.9. Cytotoxic and cellular functions of heavy metals
References
Chapter 8: Oxidative stress and oxidative damage-induced cell death
8.1. Oxidative stress
8.2. ROS regulation of signaling molecules
8.2.1. Kinases and phosphatases
8.2.2. Transcription factors
8.2.3. ROS-induced transcriptional activation
8.2.4. Signaling pathways
8.2.5. Mitogen signaling
8.2.6. Integrin signaling
8.2.7. Wnt signaling
8.3. Cellular processes regulated by ROS
8.3.1. Proliferation
8.3.2. Differentiation
8.3.3. Cell death
8.4. Autophagy and oxidative stress
8.4.1. Redox signaling in autophagy
8.5. Oxidative damage
8.6. ROS and oxidative damage on biomolecules
8.6.1. Effects of oxidative stress on lipids
8.6.2. Effects of oxidative stress on proteins
8.6.3. Effects of oxidative stress on DNA
8.7. ROS/RNS and nucleic acid destabilization
References
Chapter 9: Cell death mechanisms-Apoptosis pathways and their implications in toxicology
9.1. Apoptosis: Historical perspectives
9.2. Apoptosis: Mechanisms and different pathways
9.2.1. Extrinsic pathway
9.2.2. Intrinsic pathway
9.2.3. Perforin/granzyme pathway
9.2.4. Execution pathway
9.2.5. Main mechanisms of parasite-induced cell apoptosis
9.3. Signaling pathways leading to apoptosis in mammalian cells
9.4. The role of calcium in cell death
9.4.1. The endoplasmic reticulum, Ca2+, and apoptosis
9.4.2. Apoptosis by mitochondrial permeabilization
9.4.3. Ca2+-activated effector mechanisms
9.4.4. Ca2+ and the phagocytosis of apoptotic cells
9.5. Oxidative stress and cell death
9.6. Targets of ROS
9.7. Inflammation and cell death
9.8. Some alternative forms of cell death
9.8.1. Necrosis (type 3 cell death)
9.8.2. Autophagy
9.8.3. Pyroptosis
9.8.4. Entosis
9.8.5. Mitotic catastrophe (mitotic failure)
9.9. Links between apoptosis and other cell death modalities
9.10. Toxicity-related cell death
9.11. Role of autophagy in toxicity
9.11.1. Role of apoptosis in cancers
9.11.2. Overexpression of apoptosis
9.11.3. Use of antiapoptotic therapy agents
9.11.4. Assays used
9.12. Chelerythrine-induced cell death through ROS-dependent ER stress in human prostate cancer cells
9.12.1. CHE reduced cell viability in human prostate cancer cells
9.12.2. CHE induced cell apoptosis in human prostate cancer cells
9.12.3. CHE increased ROS accumulation in PC-3 cells
9.12.4. Blockage of ROS generation reversed CHE-induced cell apoptosis in PC-3 cells
9.12.5. CHE induced cell apoptosis through ROS-mediated ER stress in PC-3 cells
9.13. Conclusion
References
Chapter 10: Programmed cell death mechanisms and nanoparticle toxicity
10.1. Molecular mechanisms underlying nanomaterial toxicity
10.2. Major forms of programmed cell death
10.3. More than one way to skin a cat
10.4. Programmed cell death: Apoptosis
10.5. Programmed cell death: Autophagy
10.6. Programmed cell death: Necrosis
10.7. The importance of being small
10.8. Effects of nanoparticles on apoptosis
10.9. Nanomaterials and apoptosis
10.10. Nanomaterials and mitotic catastrophe
10.11. Effects of nanoparticles on autophagy
10.12. Nanomaterials and autophagy or ``autophagic cell death´´
10.13. Effects of nanoparticles on necroptosis
10.14. Nanomaterials and necrosis
10.15. Nanomaterials and pyroptosis
10.16. Mechanisms of graphene-induced programmed cell death
10.17. GBMs induce apoptosis in cells
10.18. The signaling pathways involved in GBM-induced apoptosis
10.19. GBMs induce autophagy in cells
10.20. The signaling pathways involved in GBM-induced autophagy
10.21. GBMs induce necroptosis and relative pathways involved
10.22. Some differences and relationships of GBM-induced programmed cell death
10.22.1. Differences in programmed cell death
10.22.2. Several cross-linked pathways in programmed cell death
10.23. Conclusions and perspectives
References
Chapter 11: Endoplasmic reticulum stress and associated ROS in disease pathophysiology applications
11.1. Endoplasmic reticulum
11.2. Reactive oxygen species
11.3. Sources of reactive oxygen species generation
11.4. Endoplasmic reticulum stress
11.5. Unfolded protein response
11.5.1. Inositol-requiring protein 1
11.5.2. Protein kinase-like endoplasmic reticulum kinase
11.5.3. Activating transcription factor 6
11.6. Protein folding challenge in intestinal secretory cells
11.7. Endoplasmic reticulum stress and autophagy
11.8. How are reactive oxygen species induced through endoplasmic reticulum stress?
11.8.1. The specific mechanism of ERS-induced ROS during the ER folding process
11.9. Specific mechanism of ERS-induced ROS: NADPH oxidase 4
11.10. Coupled glutathione within the ER
11.11. NADPH-dependent P450 reductase and P450 connection involvement in ERS
11.12. ER and mitochondria connection and relationship to ROS
11.13. Oxidative stress
11.14. Vicious sequence of events between endoplasmic reticulum stress and oxidative stress
11.15. Endoplasmic reticulum stress and oxidative stress in inflammatory bowel disease
11.16. Disease application
11.16.1. ERS and diseases
11.16.2. Neurodegenerative diseases
11.16.3. Diabetes mellitus
11.16.4. Atherosclerosis
11.16.5. Kinds of inflammation
11.16.6. Liver disease
11.16.7. Ischemia
11.16.8. Kidney disease
11.17. Conclusions
References
Chapter 12: Endoplasmic reticulum stress-induced cell death mechanism
12.1. ER stress and unfolded protein response
12.2. Protein folding: ER chaperones and foldases
12.2.1. General chaperones
12.2.2. Lectin chaperones
12.2.3. Other folding chaperones and enzymes
12.3. Role of ER stress inhibitors in the context of metabolic diseases
12.4. ER stress sensors
12.4.1. Activation of PERK
12.4.2. Activation of the IRE1α pathway
12.4.3. Activation of the ATF6 pathway
12.5. ER stress leads to disease progression
12.6. Metabolic disorders
12.6.1. Diabetes
12.6.2. Obesity
12.6.3. Lipid disorders
12.7. ER stress inhibitors
12.7.1. KIRA6
12.7.2. 3-Hydroxy-2-naphthoic acid
12.7.3. MKC-3946
12.7.4. 4-Phenylbutyric acid
12.7.5. Taurine-conjugated ursodeoxycholic acid
12.7.6. Olmesartan
12.7.7. N-Acetylcysteine
12.7.8. Oleanolic acid
12.7.9. Ursolic acid
12.7.10. Telmisartan
12.7.11. Quercetin
12.7.12. Other inhibitors
12.7.13. Antidiabetic drugs targeting ER stress
12.8. ER stress, UPR signaling, and cell death regulation
12.9. UPR-independent ER stress signaling and cell death
12.9.1. Calcium
12.9.2. MEKK1 (MAP3K4)
12.9.3. ER membrane reorganization
12.10. Suppressors of ER stress-induced apoptosis
12.10.1. Bax-inhibitor 1
12.10.2. Bcl-2/Bcl-XL
12.10.3. MicroRNAs
12.10.4. Additional suppressors of ER stress-induced apoptosis
12.11. ER stress and autophagy
12.12. ER stress involvement in diseases
12.12.1. Neurodegenerative diseases
12.12.2. Ophthalmology disorders
12.12.3. Immunity and inflammation
12.12.4. Viral infections
12.12.5. Metabolic diseases
12.12.6. Atherosclerosis
12.13. ER stress and cancer
12.13.1. ER chaperones and cancer regulation
12.13.2. ER sensors and cancer
12.14. The crosstalk between ER stress and autophagy in cancer
12.15. The relationship between FOXO, ER stress, and cancer
12.15.1. PERK pathway and the FOXO3 story
12.15.2. IRE-1 and FOXO regulation
12.15.3. Chaperones and FOX regulation
12.15.4. ER stress and FOX regulation in worms
12.15.5. Daf-16 and dFOXO and regulation of the Ire-1 arm
12.15.6. Regulation of PERK by dFOXO
12.16. Targeting cancer through the UPR signaling and its FOXO link
12.16.1. Targeting IRE1α/XBP1
12.16.2. Targeting PERK/ATF4
12.16.3. Chaperone inhibitors and FOXO3
References
Chapter 13: Modulation of endoplasmic reticulum (ER) stress of nanotoxicology for nanoparticles (NPs)
13.1. Nanotoxicology and nanomedicine
13.2. ER stress as a mechanism for nanotoxicology
13.2.1. Morphological changes of the ER by NP exposure
13.2.2. Effects of NP exposure on the ER stress pathway
13.2.3. Modulation of ER stress and the toxicity of NPs
13.3. Modulation of ER stress by NPs in nanomedicine
13.3.1. Selective activation of ER stress by NPs for cancer therapy
13.3.2. Alleviation of ER stress by NPs for metabolic disease therapy
13.4. Silver nanoparticles-Allies or adversaries?
13.5. Role of AgNPs in cell toxicity
13.5.1. Silver nanoparticle-induced apoptosis
13.5.1.1. Results
13.5.1.2. Conclusion
13.5.1.3. Significance
13.5.2. Silver nanoparticles induce ER stress
13.6. Uptake of AgNPs and their intracellular localization
13.7. Inhibition of proliferation and cell death
13.8. ROS key factor in biological oxidation processes
13.9. Oxidative stress as an underlying mechanism for NP toxicity
13.10. Genotoxicity
13.11. Concluding remarks
References
Chapter 14: Nanoparticle cellular uptake and intracellular targeting on reactive oxygen species (ROS) in biological activ ...
14.1. Nanoparticle classes and biomedical applications
14.1.1. Optical imaging
14.1.2. Biosensing
14.1.3. Diagnostic applications
14.1.4. Drug delivery
14.1.5. Other applications
14.2. Mechanisms associated with NP-induced ROS generation
14.2.1. NP-related factors implicated in ROS generation
14.2.2. NP- and cellular-component-induced ROS generation
14.3. Biological functions modulated by NP-induced ROS production
14.3.1. DNA damage and cytotoxicity
14.3.2. Antimicrobial function
14.3.3. Cellular differentiation
14.3.4. Anticancer
14.4. NP-induced modulation of ROS generation in stem cell biology
14.5. Nanoparticle cellular uptake and intracellular targeting
14.6. Endocytic routes and nonligand targeted nanomedicines
14.7. Receptor-mediated cellular internalization of ligand-targeted nanomedicines
14.7.1. Prostate-specific membrane antigen targeting
14.7.2. Neonatal Fc-receptor targeting-An avenue to oral delivery of nanomedicine
14.8. Intracellular trafficking and subcellular targeting
14.8.1. From endosomes/lysosomes to cytoplasm
14.8.2. Endoplasmic reticulum and Golgi apparatus
14.8.3. Mitochondria
14.8.4. Nucleus
14.9. Outlook
14.10. Conclusions
References
Chapter 15: Metal nanoparticles (MNPs) and particulate matter (PM) induce toxicity
15.1. Nano-bio interactions
15.2. Economical relevance [42a]
15.3. Nanotoxicology of nanoparticles
15.4. Overproduction of ROS and cell damage
15.5. Nanotoxicity and generation of ROS
15.6. Dependence of ROS production on the properties of nanoparticles
15.6.1. Size and shape
15.6.2. Particle surface, surface positive charges, and surface containing groups
15.6.3. Solubility and particle dissolution
15.6.4. Metal ions released from metal and metal oxide nanoparticles
15.6.5. Light activation
15.6.6. Aggregation and mode of interaction with cells
15.6.7. Inflammation leading to ROS formation
15.6.8. pH of the system
15.7. Particulate matter
References
Chapter 16: Mechanisms for nanoparticle-mediated oxidative stress
16.1. Introduction to transition metals
16.1.1. Generation of reactive oxygen species
16.1.2. Reactive oxygen species and biological systems
16.2. Exposure routes for nanoparticles
16.3. Prooxidant effects of metal oxide nanoparticles
16.4. Effects of nanoparticles on cell organisms
16.4.1. Absorption of nanoparticles and cytotoxicity
16.4.2. Absorption of nanoparticles under environmental conditions
16.4.3. Nanoparticles in outdoor spaces
16.4.4. Interactions among organisms, nanoparticles, and contaminants
16.5. Nanoparticle-induced oxidative stress
16.6. Oxidant generation via particle-cell interactions
16.6.1. Lung injury caused by nanoparticle-induced reactive nitrogen species
16.6.2. Mechanisms for reactive oxygen species production and apoptosis within metal nanoparticles
16.7. Modeling nanotoxicity
16.8. Cellular signaling affected by metal nanoparticles
16.8.1. NF-κB
16.8.2. AP-1
16.8.3. MAPK
16.8.4. PTP
16.8.5. Src
16.9. Carbon nanotubes
16.10. Carbon nanotube-induced oxidative stress
16.11. Role of reactive oxygen species in carbon nanotube-induced inflammation
16.12. Role of reactive oxygen species in carbon nanotube-induced genotoxicity
16.13. Role of reactive oxygen species in carbon nanotube-induced fibrosis
16.14. Difficulties in determination of the mechanism of nanotoxicity in cells and in vivo
16.15. Conclusion
References
Chapter 17: Nanotechnological modifications of nanoparticles on reactive oxygen and nitrogen species
17.1. Nanotechnology and nanomaterials
17.2. Nanotechnological modifications
17.2.1. Nanodiffusion in the environment
17.2.2. Nanomaterials in soil
17.2.3. Nanoparticle mobility in soil
17.3. Nanotechnology and agriculturally sustainable development
17.3.1. Nanofertilizers
17.3.2. Nanopesticides
17.3.3. Ecotoxicological implications of nanoparticles
17.4. Growth of cultivated plants and their ecotoxicological sustainability
17.5. Applications of nanotechnology in the agricultural sector
17.5.1. Nanosilver
17.5.2. Nanosilica
17.5.3. Nanotitanium dioxide
17.5.4. Nanocalcium
17.5.5. Nano-iron
17.6. Nanotechnologies in the food industry
17.6.1. Food process
17.6.2. Food packaging and labeling
17.7. Selenium nanoparticles as a food additive
17.7.1. Problems with traditional forms of oral supplementation of selenium and potential benefits of SeNPs
17.7.2. Mechanism of passage of nanoparticles through intestinal mucosa
17.7.3. Application of SeNPs through oral administration
17.7.3.1. Nano-Se as an antioxidant
17.7.3.2. Effect of SeNPs on reproductive performance
17.7.3.3. Use of nano-Se for increasing hair follicle development and fetal growth
17.7.3.4. Antiviral and antibacterial effects of SeNPs
17.7.4. Anticancer effects of SeNPs
17.7.4.1. Nano-Se as an anticancer drug
17.7.4.2. Nano-Se as an anticancer drug delivery carrier
17.7.4.3. Nano-Se as a promising orthopedic implant material and an agent reducing bone cancer cell functions
17.8. Effect of SeNPs on oxidative stress parameters
17.9. Protective effects of nano-Se
17.9.1. SeNPs in prevention of cisplatin-induced reproductive toxicity
17.9.2. Protective effect of nano-Se against polycyclic aromatic hydrocarbons
17.9.3. Use of SeNPs for minimization of risk of iron overabundance
17.9.4. SeNPs in the treatment of heavy metal intoxication
17.9.5. Nano-Se as an immunostimulatory
17.9.6. Effect of nano-Se on microbial fermentation, nutrient digestibility, and probiotic support
17.9.7. Nano-Se in the treatment of metabolic disorders
17.10. Safety and toxicity concerns of orally delivered SeNPs for use as food additives and drug carriers
References
Chapter 18: Medical imaging of the complexity of nanoparticles and ROS dynamics in vivo for clinical diagnosis application
18.1. Redox signaling
18.2. Dynamics of the EPR signal of nitroxide radicals in leukemic and normal lymphocytes
18.3. Redox-sensitive two-photon microscopy
18.3.1. Two-photon redox-sensitive probes
18.3.2. Two-photon-sensitive probes for assessment of glutathione redox state
18.3.3. Two-photon NADPH redox state-sensitive probes
18.3.4. Two-photon H2O2-sensitive probes
18.3.5. Two-photon NO-sensitive probes
18.4. Chemiluminescent imaging of ROS in vivo
18.4.1. NIR fluorescence and chemiluminescence
18.4.2. Chemiluminescent nanoparticles and ROS imaging
18.5. Ultrasound in ROS imaging
18.6. PET/SPECT in vivo imaging of oxidative stress using radiotracers
18.6.1. Imaging glucose consumption as a surrogate of oxidative stress
18.6.2. Radiotracers with redox potential-dependent cellular retention
18.6.3. Radiotracers with hypoxia-dependent cellular retention
18.6.4. Radiotracers targeting ROS scavengers or mitochondrial complex I-IV
18.7. Magnetic resonance modalities
18.7.1. Basic principles and technical considerations
18.7.2. Examples of EPRI/MRI of ROS/RNS
18.7.3. Brain imaging (without tumors)
18.7.4. Tumor imaging
18.7.5. Other organs
18.7.6. Imaging of trapped radicals
18.7.7. Dynamic nuclear polarization MRI (OMRI, PEDRI)
18.8. Dynamics of the EPR signal of Mito-TEMPO in cells of different origins and proliferative activities: Correlation wi ...
18.9. Dynamics of the EPR signal of nitroxide radical in cells of the same origin and different proliferative activities: ...
18.10. Imaging and drug delivery using theranostic nanoparticles
18.11. Imaging modality
18.11.1. Optical imaging
18.11.2. Magnetic resonance imaging
18.11.3. Radionuclide-based imaging
18.11.4. Computed tomography
18.11.5. Ultrasound
18.12. Nanoparticles
18.13. Localization of intracellular nanoparticles
18.14. Delivery of nanoparticles to the cytosol
18.15. Disturbances of intracellular transport and other cellular processes induced by nanoparticles
18.16. Cellular excretion and degradation of nanoparticles
18.17. Conclusions
18.18. Outlook
References
Chapter 19: Titanium dioxide nanoparticle-induced cytotoxicity and genotoxicity-Generation of reactive oxygen species and ...
19.1. TiO2NP-induced cytotoxicity and DNA damage
19.2. Nano-TiO2 in biological systems
19.3. TiO2NP-induced toxic effects on human health
19.4. Characterization of nano-TiO2
19.5. Nano-TiO2-induced phototoxicity in human HaCaT keratinocytes
19.6. ESR measurement of ROS generation
19.7. ESR oximetry measurement of lipid peroxidation
19.8. Immuno-spin trapping measurement of protein radicals
19.9. Phototoxic mechanism of TiO2NP-induced free radicals
19.10. Effect of dose and time of TiO2NPs on biochemical disturbance, oxidative stress, and genotoxicity
19.11. Nanosized titanium dioxide toxicity in rat prostate
19.12. Conclusion
References
Chapter 20: Toxicity of ZnO nanoparticle-induced reactive oxygen species and cancer cells
20.1. ZnO as safe NPs
20.2. Toxicological effects of ZnO NPs
20.3. Nanomedicine market overview
20.4. DDCT
20.5. CM
20.6. Effectiveness of the cervical mucus method
20.6.1. Characterization of ZnO NPs
20.6.2. Cytotoxic effect of ZnO NPs on RGC-5 cells
20.6.3. The alteration of ψm
20.6.4. DAPI staining
20.6.5. Measurement of hydrogen peroxide and hydroxyl radical levels
20.6.6. Annexin V/PI staining analysis
20.6.7. Expression of caspase-12 mRNA
20.6.8. Expression of caspase-12 protein
20.7. ZnO NP-induced ROS and ER stress causing cell damage
20.8. ZnO NPs induce apoptosis via p53 and p38 pathways
20.8.1. Apoptosis induction by ZnO NPs
20.8.2. ZnO NPs induced p53 upregulation and phosphorylation of p53 at Ser33 and Ser46
20.8.3. ZnO NPs induced p38 mitogen-activated protein kinase upregulation
20.9. Immunomodulatory effects of ZnO NPs
20.9.1. Cellular uptake of ZnO NPs
20.9.2. Cytotoxicity assessment
20.9.3. Evaluation of oxidative stress
20.9.4. Cytokine quantitation
20.9.5. Western blot analysis
20.9.6. Genotoxic potential of ZnO NPs
20.10. Selective toxicity of ZnO NPs and cancer cells
20.11. Conclusion
References
Chapter 21: Silver nanoparticles induce cellular cytotoxicity, genotoxicity, DNA damage, and cell death
21.1. Toxicology of AgNPs
21.1.1. Cytotoxicity of AgNP suspensions strongly depends on the silver ion concentration
21.2. AgNPs induce cytotoxicity
21.2.1. Stability of AgNPs in culture media
21.2.2. Cytotoxicity in cultured RAW264.7 cells
21.2.3. Cell-cycle changes
21.2.4. Decreased intracellular glutathione level
21.2.5. Increased nitric oxide level
21.2.6. Increased protein level and gene expression of tumor necrosis factor-α
21.2.7. Increased gene expression of matrix metalloproteinases
21.2.8. Transfer of AgNPs into RAW264.7 cells
21.3. Oxidative DNA damage of human cells treated with AgNPs
21.3.1. Silver ion release from 20nm AgNP in culture media
21.3.2. Nanoparticle uptake and formation of reactive oxygen species in AgNP-treated cells
21.3.3. DNA breakage and base damage
21.3.4. Clonogenic survival
21.4. Cytotoxicity and genotoxicity of AgNPs
21.4.1. Cellular uptake and intracellular localization of AgNPs
21.4.2. Mitochondrial activity and production of reactive oxygen species
21.5. Cyto- and genotoxic potential of AgNPs in hMSCs
21.5.1. Particle characterization
21.5.2. Cell viability
21.5.3. Genotoxicity
21.5.4. Cytokine secretion
21.5.5. Migration assay
21.6. Cellular toxicity and morphological alterations caused by AgNPs
21.7. Conclusions
References
Chapter 22: Correlations between oxidative stress and aligning nanoparticle safety assessments
22.1. Aligning nanomaterial safety assessments with the 3Rs principles
22.2. Nanomaterial mechanism of toxicity
22.3. Nanomaterials and inflammation
22.3.1. Neutrophils
22.3.2. Macrophages
22.4. Nanomaterials and oxidative stress
22.5. Alternative models to investigate nanomaterial-mediated inflammogenicity and oxidative stress
22.5.1. Zebrafish
22.5.1.1. Zebrafish and the innate immune response to nanomaterials
22.5.1.2. Zebrafish embryos and oxidative stress
22.5.1.3. Zebrafish: Recommendations for a testing strategy
22.5.1.3.1. Life stage
22.5.1.3.2. Route of administration
22.5.2. In vitro models
22.5.3. In vitro to in vivo extrapolation
22.6. Conclusions
References
Chapter 23: Effects of interactions between antioxidant defense therapy and ROS
23.1. Enzymatic antioxidants
23.1.1. A toxin and its action via ROS
23.1.2. Antioxidant systems as redox signal transmitters
23.2. Nonenzymatic antioxidants
23.2.1. Vitamin C (ascorbic acid)
23.2.2. Vitamin E (α-tocopherol)
23.2.3. Glutathione
23.2.4. Melatonin
23.2.5. Carotenoids (β-carotene)
23.3. Antioxidants and their mode of action
23.4. ROS can promote pathogen elimination by direct oxidative damage or by a variety of innate and adaptive mechanisms
23.4.1. Direct oxidative damage to microbes
23.4.2. O2- promotes proteolytic elimination of microorganisms indirectly
23.4.3. ROS promote autophagy
23.4.4. ROS inhibit mTOR kinase, triggering an antiviral response
23.4.5. ROS promote NETosis
23.4.6. ROS promote cell death of infected reservoirs
23.4.7. PRRs use ROS as signaling intermediaries in inflammation
23.4.8. ROS are chemoattractors to phagocytes
23.4.9. ROS can activate NRF2 target genes, a part of the antioxidant defense response that interferes with innate immunity
23.4.10. ROS interfere with iron storage and tissue mobilization, influencing iron availability to pathogens
23.4.11. ROS interfere with lipid metabolism and foam cell formation
23.4.12. ROS influence phagosomal proteolysis through cathepsin inactivation
23.4.13. ROS interfere with protein immunogenicity, antigenic presentation, polarization, and costimulation by dendritic ...
23.5. Antioxidant defense toward ROS
23.6. Counteractive antioxidant defense
23.7. Cellular defense against ROS
23.8. Metal chelators as an algal response to heavy metals
23.8.1. l-Cys and N-acetyl cysteine
23.8.2. Taurine
23.8.3. Dietary antioxidants
23.8.4. α-Lipoic acid
23.9. Essential mineral ions
23.9.1. Selenium
23.9.2. Iron
23.9.3. Copper
23.9.4. Zinc
23.10. Redox biology and oxidative stress
23.11. The role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses
23.11.1. ABC transporters and active cholesterol efflux
23.11.1.1. ABCA1 and cholesterol efflux to apoA-I
23.11.1.2. ABCG1 and cholesterol efflux to mature HDL
23.11.2. ABC transporters and the molecular regulation of the immune system
23.11.2.1. Transporters and macrophage inflammation
23.11.2.2. ABC transporters and lymphocyte proliferation
23.11.3. ABC transporters and in vivo relevance of the regulation of the immune system: A role in atherosclerosis and oth ...
23.11.3.1. ABC transporters and atherosclerosis
23.11.3.2. ABC transporters and inflammatory diseases
23.12. Response of the antioxidant enzymes of nanoparticles
23.12.1. Response of erythrocytes to NPs
23.12.2. Response of serum biomarkers to NPs
References
Chapter 24: FDA breakthrough-Drug therapy designations for clinical evidence
24.1. Breakthrough therapy
24.1.1. Requirements
24.1.2. Incentives
24.1.3. Issues
24.2. Frequently asked questions: Breakthrough therapies
24.2.1. How many requests for breakthrough therapy designation has the FDAs Center for Drug Evaluation and Research and C ...
24.2.2. What are the benefits of a breakthrough therapy designation?
24.2.3. What other programs does FDA have to expedite for drug development for serious conditions?
24.2.3.1. Fast track designation
24.2.3.2. Accelerated approval
24.2.3.3. Priority review
24.2.4. What are the differences between the criteria for breakthrough therapy designation and fast track designation?
24.2.5. Is there a deadline for a sponsor to submit a request for breakthrough therapy designation?
24.2.6. Does a sponsor have to request breakthrough therapy designation to be considered for the designation?
24.2.7. Where can I find the ``Guidance for Industry´´ on breakthrough therapies?
24.2.8. Where can I find the CDER Manual of Policies and Procedures (MAPP) on the management of breakthrough therapy-desi ...
24.2.9. Where can I find the CDER Manual of Policies and Procedures (MAPP) on the review of a marketing application for a ...
24.2.10. Where can I find the CBER Standard Operating Policy and Procedure (SOPP) on the management of breakthrough thera ...
24.2.11. Where can I find the webcast and presentations from the FDA public meeting: Breakthrough therapy designation: Ex ...
24.2.12. Can a sponsor submit a request for breakthrough therapy designation for multiple indications of the same drug?
24.2.13. Can a request for a breakthrough therapy designation be submitted for a combination product?
24.2.14. Can a product be granted a breakthrough therapy designation if another product has already been granted breakthr ...
24.2.15. Whom should sponsors contact if they wish to discuss the potential for their product meeting the breakthrough th ...
24.2.16. Would a clinical trial for a drug that has been designated as a breakthrough therapy generally have to enroll fe ...
24.2.17. May a sponsor submit a request for Special Protocol Assessment (SPA) for a drug that has breakthrough therapy de ...
24.2.18. Will FDA announce when a drug has been granted breakthrough therapy designation?
24.2.19. If a drug is denied breakthrough therapy designation, is it automatically reviewed for fast track designation?
24.2.20. To what section of the electronic Common Technical Document should a sponsor submit a request for breakthrough t ...
24.2.21. Can a sponsor submit a request for breakthrough therapy designation to a pre-IND?
24.2.22. What are the timelines for FDA to respond to a breakthrough therapy designation request?
24.2.23. Can a sponsor get preliminary breakthrough therapy designation (BTD) advice from the review division prior to th ...
24.2.24. The European Medicines Agency (EMA) PRIME program, similar to the FDA breakthrough therapy designation program, ...
24.3. List of drugs granted breakthrough therapy designation [13-17]
24.3.1. Why screening with an FDA-approved drug library?
24.4. Energy metabolism and cellular toxicity
24.5. Navigating metabolic pathways to enhance antitumor immunity
24.6. Conclusion and future directions
24.6.1. Future perspectives
24.6.2. Hackathon homes in on RNA
References
List of abbreviations
Index
Back Cover