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Showing papers in "Current Opinion in Toxicology in 2018"


Journal ArticleDOI
TL;DR: Sies et al. as discussed by the authors defined a global concept of Oxidative Stress as an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage.

169 citations


Journal ArticleDOI
TL;DR: Specific examples whereby ROS generated by CYPs contribute to or protect against various phenomena, such as hyperoxic lung injury, oxidative hepatic toxicity, formation of DNA adducts from lipid peroxidation products are discussed.

148 citations


Journal ArticleDOI
TL;DR: Further elucidation of the relationship between changes in cell redox and thiol reactivity could provide a better understanding of how redox changes regulate cell function and how disruption of these relationships lead to tissue injury and dysfunction and the development of chronic diseases such as cancer and cardiovascular disease.

105 citations


Journal ArticleDOI
TL;DR: Findings suggest that formaldehyde might be a driver of the human disease FA, and links this genotoxin to the etiology of other human illnesses, such as the Ruijs-Aalfs syndrome and the cancer predisposition of BRCA2 mutation carriers.

79 citations


Journal ArticleDOI
TL;DR: The conceptual basis of the AOP framework is described and aspects of its current status relative to use by toxicologists and risk assessors are described, including four illustrative applications of the framework to diverse assessment scenarios.

73 citations


Journal ArticleDOI
TL;DR: Although the field has made great strides in describing oxidative DNA damage and improving the overall sensitivity of standard techniques, many questions are still unanswered and substantial technical challenges remain; differential quantification and description of DNA damage (mitochondrial vs. nuclear) continues to be a challenge and a priority going forward.

66 citations


Journal ArticleDOI
TL;DR: The discovery that Th17-dependent inflammation is significantly attenuated in RORγ-deficient mice in several experimental autoimmune disease models, initiated a search for ROR modulators that led to the identification of a number of small molecular weight R ORγ inverse agonists.

65 citations


Journal ArticleDOI
TL;DR: This data indicates that chronic oxidative stress can induce protective pathways lowering genotoxicity, and mitochondria lack nucleotide excision repair, which is critical for the understanding of a wide range of human disorders.

65 citations


Journal ArticleDOI
TL;DR: The lung evolved as an organ that can efficiently promote gas exchange for the entire organism but as such, the lung is highly susceptible to its external environment and the vulnerability of the lung to oxidative stress is acknowledged.

62 citations


Journal ArticleDOI
TL;DR: The sources of reactive oxygen, the oxidants involved and the impact of this oxidant stress in the mechanism of cell death in 3 different clinically relevant acute liver injury models are discussed.

59 citations


Journal ArticleDOI
TL;DR: The susceptibility to human cancers can be modified by polymorphisms in oxidative DNA repair genes and antioxidant genes, as well as xenobiotics, pharmaceuticals and radiation.

Journal ArticleDOI
TL;DR: One important role for NQO1 when induced under stress is to maintain the stability of critical proteins such as p53 and other transcription factors, as well as reducing superoxide directly and participating in protein-protein interactions.

Journal ArticleDOI
TL;DR: Live-cell imaging has proven to be a powerful approach to the study of environmental oxidative stress, and cells are equipped with multiple complementary energy-dependent systems for maintaining redox homeostasis in the face of environmental antioxidant stress.

Journal ArticleDOI
TL;DR: The mechanisms by which ROS directly and indirectly activate autophagy, and conversely, how selective autophile suppresses ROS are described, to highlight what appear to be contradictory examples.

Journal ArticleDOI
TL;DR: Like ligands for other receptors, AhR ligands are selective AhR modulators (SAhRMs) which exhibit variable tissue-, organ- and species-specific genomic and functional activities.

Journal ArticleDOI
TL;DR: This Opinion paper aims to discuss the current state of knowledge regarding how mTOR and AMPK regulate the metabolism and survival of brain cells and the close interrelationship between both signaling cascades.

Journal ArticleDOI
TL;DR: Key studies and challenges in understanding cellular mechanisms of ENM-mediated immunomodulation and toxicity are highlighted.

Journal ArticleDOI
TL;DR: The review not only provides an overview of the current knowledge and evidence showing strong associations between environmental exposures, OS, and ADs, but also plausible mechanisms by which OS causes autoimmunity/ADs.

Journal ArticleDOI
TL;DR: Whether metabolomics might constitute a relevant tool to discover new early biomarkers of effects related to chemical exposure in humans is investigated to provide more relevant information on both chemical exposure and metabolic signatures of environmental contaminants.

Journal ArticleDOI
TL;DR: Understanding the contribution of toxicants to diabetes risk as well as improved understanding of their mechanisms of action offer unique opportunities to modulate diabetes risk via targeted therapeutics or public policy interventions to reduce and remediate exposures.

Journal ArticleDOI
TL;DR: The current progress in the studies of metabolic reprogramming and Cr(VI) carcinogenesis is summarized with emphasis on the metabolic enzymes and oxidative stress related major oncogenic pathways.

Journal ArticleDOI
TL;DR: Untargeted metabolomics should complement targeted methods for quantitative and reliable analysis of exposome compounds in biological matrices and environmental effects on endogenous metabolites can be assessed by accurate and comprehensive exposure analysis.

Journal ArticleDOI
TL;DR: It is argued that localized tissue damage and chronic inflammation elicited by xenobiotic exposure leads to the release of self-antigens and damage-associated molecular patterns as well as the appearance of ectopic lymphoid structures and secondary lymphoid hypertrophy, which provide a milieu for the production of autoreactive B and T cells that contribute to the development and persistence of autoimmunity in predisposed individuals.

Journal ArticleDOI
TL;DR: Endogenous steroid hormones and endocrine disrupting compounds (EDC) can significantly affect the immune responses, influencing the initiation of the immune response and the maintenance of peripheral tolerance to self-antigens.

Journal ArticleDOI
TL;DR: This review presents key gut microbiome research areas, with a focus on metabolism of xenobiotics by the gut microbiome, and presents new avenues to determine the role of microbiomes in the toxicity of chemicals.

Journal ArticleDOI
TL;DR: The role of endocrine disruption in DIT is considered and endocrine disrupting chemicals (EDCs) with known DIT effects are highlighted, of special importance are microglia, the resident immune cells of the central nervous system that are highly influenced by endogenous endocrine signals during development and are therefore sensitive to effects from exposure to EDCs.

Journal ArticleDOI
TL;DR: The purpose of this review is to summarize the current knowledge of the impact of arsenic on the immune system and suggest that the immunosuppressive effects of arsenic efficiently prevent or treat severe immune-related diseases.

Journal ArticleDOI
TL;DR: In this article, the authors discuss integration of the AOP and AEP frameworks and how such integration can improve confidence in both traditional and cumulative risk assessment approaches, and discuss the integration of these frameworks with the FAIR (i.e., findable, accessible, interoperable and reusable) principle.

Journal ArticleDOI
TL;DR: Current insights into the mechanisms underlying the diversity of effects of PAHs (or their mixtures) on steroid signaling are discussed, focusing on the role of crosstalk between estrogen receptors and the aryl hydrocarbon receptor, direct effects ofPAHs on estrogen signaling, and on the contribution of metabolism to estrogen-like effects of some PAHS.

Journal ArticleDOI
TL;DR: This review focuses on some of the mechanisms that underlie OS-induced reproductive toxicity at the cellular- and organ levels (germ cell damage and perturbed organ responses to endocrine stimuli) and the adoption of therapeutic strategies, including but not limited to administering phytochemicals to improve disease outcomes.