The Current Opinion journals were developed out of the recognition that it is increasingly difficult for specialists to keep up to date with the expanding volume of information published in their subject. Elsevier’s Current Opinion journals comprise of 26 leading titles in life sciences and adjacent fields.

Current Opinion in Toxicology

Issues per year: 6 issues
Editorial Board

Current Opinion in Toxicology

The aims and scope of Current Opinion in Toxicology is to systematically provide the reader with timely and provocative views and opinions of the highest qualified and recognized experts on current advances in selected topics within the field of toxicology. The goal is that Current Opinion in Toxicology will be an invaluable source of information and perspective for researchers, teachers, managers and administrators, policy makers and students.

Division of the subject into sections:

For this purpose, the scope of Toxicology is divided into six selected high impact themed sections, each of which is reviewed once a year:

  • Mechanistic Toxicology
  • Metabolic Toxicology
  • Risk assessment in Toxicology
  • Genomic Toxicology
  • Systems Toxicology
  • Translational Toxicology

Best Cited over the last year.

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The multifaceted role of Nrf2 in mitochondrial function

© 2016 The Authors The transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the master regulator of the cellular redox homeostasis. Nrf2 target genes comprise of a large network of antioxidant enzymes, proteins involved in xenobiotic detoxification, repair and removal of damaged proteins, inhibition of inflammation, as well as other transcription factors. In recent years it has emerged that as part of its role as a regulator of cytoprotective gene expression, Nrf2…

Volume 2, Issue , 01 January 2017, Pp 80-91
Kira M. Holmström | Rumen V. Kostov | Albena T. Dinkova-Kostova

Diversity as opportunity: Insights from 600 million years of AHR evolution

© 2017 Elsevier B.V. The aryl hydrocarbon receptor (AHR) was for many years of interest only to pharmacologists and toxicologists. However, this protein has fundamental roles in biology that are being revealed through studies in diverse animal species. The AHR is an ancient protein. AHR homologs exist in most major groups of modern bilaterian animals, including deuterostomes (chordates, hemichordates, echinoderms) and the two major clades of protostome invertebrates [ecdysozoans (e.g.…

Volume 2, Issue , 01 January 2017, Pp 58-71
Mark E. Hahn | Sibel I. Karchner | Rebeka R. Merson

Shadows of NRF2 in cancer: Resistance to chemotherapy

© 2016 Elsevier B.V. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) plays a crucial role in the upregulation of a wide array of genes that are associated with the maintenance of intracellular redox homeostasis and xenobiotic detoxification. Although the beneficial effects of NRF2 activation have been demonstrated in various healthy cell systems, there is substantial evidence demonstrating the negative aspect of NRF2 in cancers. In this review, we discuss the evidence supporting that…

Volume 1, Issue , 01 January 2016, Pp 20-28
Bo hyun Choi | Mi Kyoung Kwak

Roles of Nrf2 in drug and chemical toxicity

© 2016 Elsevier B.V. The transcription factor Nrf2 regulates the basal and inducible expression of numerous cell defence genes, and thus protects mammalian cells against the deleterious effects of chemical and oxidative stress. Here, we provide a concise overview of the role of Nrf2 in protection against drug and chemical toxicity, with a focus on the numerous in vivo studies that have shown heightened sensitivity of Nrf2 null (knockout) transgenic mice to such insults. In light of the emerging…

Volume 1, Issue , 01 January 2016, Pp 104-110
Jessica L. Clarke | James B. Murray | B. Kevin Park | Ian M. Copple

And now for something completely different: Diversity in ligand-dependent activation of Ah receptor responses

© 2017 Ligand-dependent activation of the Ah receptor (AhR) can result in an extremely diverse spectrum of biological and toxic effects that occur in a ligand-, species- and tissue-specific manner. While the classical mechanism of AhR-dependent signal transduction is directly related to its ability to modulate gene expression, the dramatic diversity in responses observed following AhR activation or inhibition is inconsistent with a single molecular mechanism of AhR action. Recent studies have…

Volume 2, Issue , 01 February 2017, Pp 124-131
Michael S. Denison | Samantha C. Faber

The complex role of NRF2 in cancer: A genomic view

© 2016 Heterotrophs are regularly exposed to harmful xenobiotics from their diet and from environmental exposure. As such, systems to counteract the negative consequences brought on by this exposure have evolved since the dawn of heterotrophic nutrition. In mammalian cells, the CNC transcription factor, NRF2, plays a crucial role in counteracting the harmful effects of xenobiotics exposure. In response to increased electrophilic and oxidative stresses, NRF2 upregulates a wide array of target…

Volume 1, Issue , 01 January 2016, Pp 37-45
Brandon John Praslicka | Michael John Kerins | Aikseng Ooi

Regulation of the Keap1–Nrf2 pathway by p62/SQSTM1

© 2016 The Authors Nrf2 is a transcription factor responsible for gene expression of a series of anti-oxidant proteins and detoxifying enzymes. Keap1, an adaptor protein of Cullin-3 ubiquitin ligase, senses electrophilic or oxidative stresses and then arrests ubiquitination of Nrf2, leading to Nrf2 activation. In addition to this canonical pathway, one Nrf2 target (p62/SQSTM1) competitively binds to Keap1 to activate Nrf2. The p62/SQSTM1-Keap1-Nrf2 axis is linked to selective autophagy and…

Volume 1, Issue , 01 January 2016, Pp 54-61
Yoshinori Katsuragi | Yoshinobu Ichimura | Masaaki Komatsu

Gene regulatory effects of disease-associated variation in the NRF2 network

© 2016 The Authors Reactive oxygen species (ROS), which are both a natural byproduct of oxidative metabolism and an undesirable byproduct of many environmental stressors, can damage all classes of cellular macromolecules and promote diseases from cancer to neurodegeneration. The actions of ROS are mitigated by the transcription factor NRF2, which regulates expression of antioxidant genes via its interaction with cis-regulatory antioxidant response elements (AREs). However, despite the…

Volume 1, Issue , 01 January 2016, Pp 71-79
Sarah E. Lacher | Matthew Slattery

Overview of redox regulation by Keap1–Nrf2 system in toxicology and cancer

© 2016 Elsevier B.V. The Keap1–Nrf2 pathway is a cellular defense system against oxidative and xenobiotic stresses derived from reactive oxygen species (ROS) and electrophiles, respectively. Nrf2 is a key transcription factor that activates a set of cytoprotective genes, including those encoding antioxidative and detoxifying enzymes. Keap1 is an adaptor protein of Cullin3-based E3 ligase, which regulates Nrf2 activity in response to these stresses. Under unstressed conditions, Keap1…

Volume 1, Issue , 01 January 2016, Pp 29-36
Mikiko Suzuki | Akihito Otsuki | Nadine Keleku-Lukwete | Masayuki Yamamoto

Is chronic AhR activation by rapidly metabolized ligands safe for the treatment of immune-mediated diseases?

© 2017 Elsevier B.V. There is a long standing perception that AhR ligands are automatically disqualified from pharmaceutical development due to their induction of Cyp1a1 as well as their potential for causing “dioxin-like” toxicities. However, recent discoveries of new AhR ligands with potential therapeutic applications have been reported, inviting reconsideration of this policy. One area of exploration is focused on the activation of AhR to promote the generation of regulatory T cells,…

Volume 2, Issue , 01 January 2017, Pp 72-78
Allison K. Ehrlich | Nancy I. Kerkvliet

The aryl hydrocarbon receptor (AhR) as a drug target for cancer chemotherapy

© 2017 Elsevier B.V. The aryl hydrocarbon receptor (AhR) is overexpressed in some patients with different tumor types, and the receptor can be a negative or positive prognostic factor. There is also evidence from both in vivo and in vitro cell culture models that the AhR can exhibit tumor-specific pro-oncogenic and tumor suppressor-like functions and therefore can be treated with AhR antagonists or agonists, respectively. Successful clinical applications of AhR ligands will require the…

Volume 1, Issue , 01 January 2016, Pp 24-29
Stephen Safe | Yating Cheng | Un Ho Jin

Progress in identifying epigenetic mechanisms of xenobiotic-induced non-genotoxic carcinogenesis

© 2017 Elsevier B.V. Determining the human relevance of structurally and functionally distinct non-genotoxic carcinogenic compounds that induce a diverse range of tissue-, gender-, strain- and species-specific tumours in animals remains a major challenge for toxicologists. Nevertheless, elucidating mechanisms of xenobiotic-induced tumours in animals can provide industry, environmental and regulatory scientists with valuable tools for cancer hazard identification and risk assessment. The…

Volume 3, Issue , 01 April 2017, Pp 62-70
Rémi Terranova | Antonio Vitobello | Alberto Del Rio Espinola | C. Roland Wolf | Michael Schwarz | John Thomson | Richard Meehan | Jonathan Moggs

NRF2-targeted therapeutics: New targets and modes of NRF2 regulation

© 2016 Elsevier B.V. Pharmacological activation of the transcription factor nuclear factor-erythroid derived 2-like 2 (NRF2), the key regulator of the cellular antioxidant response, has been recognized as a feasible strategy to reduce oxidative/electrophilic stress and prevent carcinogenesis or other chronic illnesses, such as diabetes and chronic kidney disease. In contrast, due to the discovery of the “dark side” of NRF2, where prolonged activation of NRF2 causes tissue damage, cancer…

Volume 1, Issue , 01 January 2016, Pp 62-70
Montserrat Rojo de la Vega | Matthew Dodson | Eli Chapman | Donna D. Zhang

Nrf2 in Type 2 diabetes and diabetic complications: Yin and Yang

© 2016 Elsevier B.V. Type 2 diabetes (T2D) is a metabolic disease that is attributed to a combination of genetic, lifestyle and environmental factors. There is compelling evidence that oxidative stress plays critical roles in the two key events in the pathogenesis of T2D: insulin resistance and pancreatic β-cell dysfunction. Although cytotoxic, reactive oxygen species (ROS) also function as important intracellular signaling molecules involved in insulin signaling and glucose sensing. Too many…

Volume 1, Issue , 01 January 2016, Pp 9-19
Jingqi Fu | Yongyong Hou | Peng Xue | Huihui Wang | Yuanyuan Xu | Weidong Qu | Qiang Zhang | Jingbo Pi

Regulation of Keap1–Nrf2 signaling: The role of epigenetics

© 2016 Elsevier B.V. Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (NFE2L2/Nrf2) signaling pathway is a pivotal player in the antioxidant response to oxidative and electrophilic stress and can play a role in many human diseases. Activation or inhibition of Nrf2 has been an approach to treating many diseases such as cancer and regulation of this pathway has been thoroughly studied. Recently, epigenetics has emerged as another layer for regulating…

Volume 1, Issue , 01 January 2016, Pp 134-138
David Cheng | Renyi Wu | Yue Guo | Ah Ng Tony Kong

The aryl hydrocarbon receptor as a moderator of host-microbiota communication

© 2017 Elsevier B.V. The aryl hydrocarbon receptor (AHR) is an important component of the host-microbiota communication network. Comparisons of wild-type and Ahr-null mice as well as from exposure studies with potent AHR ligands (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin) have provided compelling evidence that the AHR may be a master regulator of the host-microbiota interaction thus helping to shape the immune system and impact host metabolism. Metabolomics and sequenced-based microbial…

Volume 2, Issue , 01 January 2017, Pp 30-35
Limin Zhang | Robert G. Nichols | Andrew D. Patterson

Quantitative systems toxicology

© 2017 The Authors The overarching goal of modern drug development is to optimize therapeutic benefits while minimizing adverse effects. However, inadequate efficacy and safety concerns remain to be the major causes of drug attrition in clinical development. For the past 80 years, toxicity testing has consisted of evaluating the adverse effects of drugs in animals to predict human health risks. The U.S. Environmental Protection Agency recognized the need to develop innovative toxicity testing…

Volume 4, Issue , 01 June 2017, Pp 79-87
Peter Bloomingdale | Conrad Housand | Joshua F. Apgar | Bjorn L. Millard | Donald E. Mager | John M. Burke | Dhaval K. Shah

Development of Keap1-interactive small molecules that regulate Nrf2 transcriptional activity

© 2016 Elsevier B.V. There has been considerable progress recently in the discovery and development of Keap1-interactive compounds that enhance Nrf2 transcriptional activity. The compounds fall into two broad classes: electrophilic cysteine-reactive compounds and non-electrophilic Keap1-Nrf2 protein–protein interaction inhibitors. This short review highlights structures from both classes and discusses their development, biological properties, and the future prospects for developing therapeutic…

Volume 1, Issue , 01 January 2016, Pp 1-8
Nikolaos D. Georgakopoulos | Jemma Gatliff | Geoff Wells

Epigenetics in chemical-induced genotoxic carcinogenesis

© 2017 Elsevier B.V. The relationship between genotoxicity and cancer has been extensively demonstrated and is well accepted; however, the role of epigenetic regulators that are involved in genotoxic events and carcinogenic processes is less understood. Epigenetic mechanisms are known to play important roles in carcinogenesis, and connections between epigenetics and DNA damage and repair have been reported. This mini review discusses some of the known relationships between epigenetic mechanisms…

Volume 6, Issue , 01 October 2017, Pp 10-17
Grace A. Chappell | Julia E. Rager

Insights into the role of NRF2 in cancer provided by cancer genomics

© 2016 Elsevier B.V. Accumulating evidence suggests that NRF2 is commonly overactive in cancer, and that unchecked NRF2 activity in cancer cells promotes cell proliferation and resistance to cell death, two hallmarks of cancer. High throughput genomic techniques have enabled large scale molecular characterization of patient derived tumor samples, providing a global view of molecular mechanisms of cancer. In this review, we will discuss how large-scale multi-omics cancer projects, such as The…

Volume 1, Issue , 01 January 2016, Pp 111-117
Petri Pölönen | Anna Liisa Levonen

Molecular modeling of the AhR structure and interactions can shed light on ligand-dependent activation and transformation mechanisms

© 2017 Elsevier B.V. Molecular modeling has given important contributions to elucidation of the main stages in the AhR signal transduction pathway. Despite the lack of experimentally determined structures of the AhR functional domains, information derived from homologous systems has been exploited for modeling their structure and interactions. Homology model s of the AhR PASB domain have provided information on the binding cavity and contributed to elucidate species-specific differences in…

Volume 1, Issue , 01 January 2016, Pp 42-49
Laura Bonati | Dario Corrada | Sara Giani Tagliabue | Stefano Motta

Sex-specific metabolic alterations induced by environmental pollutants

© 2017 Elsevier B.V. Diabetes and obesity are the biggest public health challenge and the current prevalence of these chronic diseases has reached epidemic proportions worldwide. Apart from genetic alterations and lifestyle, exposure to environmental chemicals has emerged as a new cause of metabolic diseases. Notably, several compounds that mimic or oppose hormone activity defined as endocrine disruptors (EDs), may exert metabolic disturbances through interfering with the regulatory roles of…

Volume 8, Issue , 01 April 2018, Pp 1-7
Brigitte Le Magueresse-Battistoni | Hubert Vidal | Danielle Naville

Future of developmental toxicity testing

© 2017 The Author Protection of developing offspring from the potential adverse effects of in utero exposures is an important aspect of the safety profile for medicines, chemicals and physical agents. The standard safety test design for this type of endpoint was developed in the mid-1960's and has changed little in the ensuing half-century. While embryo-fetal development studies have done a good job of protecting pregnant women and their babies, the tests are labor intensive, time consuming and…

Volume 3, Issue , 01 April 2017, Pp 1-5
John M. DeSesso

Regulation of the CNC-bZIP transcription factor Nrf2 by Keap1 and the axis between GSK-3 and β-TrCP

© 2016 Elsevier B.V. The transcription factor NF-E2 p45-related factor 2 (Nrf2) mediates adaptation to oxidative stress by inducing cytoprotective genes including heme oxygenase-1 (HMOX1) and NAD(P)H:quinone oxidoreductase-1 (NQO1). Nrf2 is principally controlled by Kelch-like ECH-associated protein 1 (Keap1), which allows constitutive ubiquitylation and rapid degradation of Nrf2 by the cullin-3 (Cul3)-RING ubiquitin ligase CRL Keap1 under non-stressed conditions. Simultaneously, glycogen…

Volume 1, Issue , 01 January 2016, Pp 92-103
John D. Hayes | Kimimuepigha Ebisine | Ritu S. Sharma | Sudhir Chowdhry | Albena T. Dinkova-Kostova | Calum Sutherland

The diverse and important contributions of the AHR to cancer and cancer immunity

© 2017 With regard to its role in cancer, the AHR was originally described as a sensor of environmental carcinogens that, once activated, up-regulated monooxygenases responsible for the production of mutagenic metabolites. However, the AHR now appears to be play an ongoing role in cancer progression and tumor immunity. High AHR levels and constitutive activity in many types of cancers are consistent with the AHR's contribution to tumor progression. Here, we postulate that constitutive AHR…

Volume 2, Issue , 01 January 2017, Pp 93-102
Zhongyan Wang | Stefano Monti | David H. Sherr