Chloracne and Hyperpigmentation Caused by Exposure to Hazardous Aryl Hydrocarbon Receptor Ligands

Dioxins and dioxin-like compounds are environmental pollutants that are hazardous to human skin. They can be present in contaminated soil, water, and air particles (such as ambient PM2.5). Exposure to a high concentration of dioxins induces chloracne and hyperpigmentation. These chemicals exert their toxic effects by activating the aryl hydrocarbon receptor (AHR) which is abundantly expressed in skin cells, such as keratinocytes, sebocytes, and melanocytes. Ligation of AHR by dioxins induces exaggerated acceleration of epidermal terminal differentiation (keratinization) and converts sebocytes toward keratinocyte differentiation, which results in chloracne formation. AHR activation potently upregulates melanogenesis in melanocytes by upregulating the expression of melanogenic enzymes, which results in hyperpigmentation. Because AHR-mediated oxidative stress contributes to these hazardous effects, antioxidative agents may be potentially therapeutic for chloracne and hyperpigmentation

Punctuated growth of an accretionary prism and the onset of a seismogenic megathrust in the Nankai Trough

Abstract Ocean drilling in the Nankai Trough forearc suggests a new scenario for the evolution of the Nankai subduction zone. Continuous subduction since the Late Cretaceous has been a common tectonic scenario, although the plate subduction was transferred from the Pacific Plate to the Philippine Sea Plate during the Miocene. Seismic reflection studies coupled with drilling have demonstrated that two episodes have controlled the recent evolution of the Nankai forearc: a resurgence of subduction at ~ 6 Ma after cessation since ~ 12 Ma and rapid growth of the accretionary prism since ~ 2 Ma because of the influx of large amounts of terrigenous sediments from the Japan Alps in central Japan. Both episodes were synchronous with large-scale plate reorganizations. The westward subduction of the Philippine Sea Plate initiated both in the Ryukyu and the Philippine trenches at ~ 6 Ma. Rifting in the Okinawa and Mariana troughs started at ~ 6 Ma. Compressive tectonics in northeast Japan started at ~ 3–2 Ma, and resultant mountain building with active surface erosion commenced in central Japan at ~ 2 Ma. This recent compressive tectonic phase might be due to the initiation of convergence of the Amurian Plate with the Okhotsk or North American Plate along the eastern margin of the Japan Sea. In addition to this event, the strong collision and indentation of the Izu-Bonin Arc since ~ 2.5 Ma was also enhanced in central Japan

Antioxidative Phytochemicals Accelerate Epidermal Terminal Differentiation via the AHR-OVOL1 Pathway: Implications for Atopic Dermatitis

Aryl hydrocarbon receptor (AHR) is a chemical sensor that is expressed abundantly in epidermal keratinocytes. Oxidative AHR ligands induce the production of reactive oxygen species. However, antioxidant AHR ligands inhibit reactive oxygen species generation via activation of nuclear factor-erythroid 2-related factor-2, which is a master switch for antioxidative signalling. In addition, AHR signalling accelerates epidermal terminal differentiation, but excessive acceleration by oxidative ligands, such as dioxins, may induce chloracne and inflammation. However, antioxidative phytochemical ligands induce the beneficial acceleration of epidermal differentiation that repairs skin barrier disruption. The upregulated expression of differentiation molecules, such as filaggrin, is mediated via the AHR-OVOL1 axis. This AHR-OVOL1 system is capable of counteracting skin barrier dysfunction in T-helper type 2-shifted inflammation. This article reviews the dynamic and multifaceted role of AHR in epidermal biology and discusses the potential use of antioxidative phytochemical ligands for AHR in inflammatory skin diseases, such as atopic dermatitis

Aryl Hydrocarbon Receptor and Dioxin-Related Health Hazards—Lessons from Yusho

Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho

Identification of the static backstop and its influence on the evolution of the accretionary prism in the Nankai Trough

To reveal the origin of a backstop and its influence on the evolution of the accretionary prism, we analyzed reflection seismic data acquired in the Nankai Trough off the Kii Peninsula. The deformation features of the forearc basin sequence show that the landward accretionary prism close to the coast was not deformed after the development of the forearc basin about 2–4 Ma. The surface of the landward prism can be identified as strong amplitude reflector, indicating that the landward prism has higher seismic velocity. Therefore, the landward accretionary prism inferred to be of higher strength constitutes a static backstop. Based on seismic and geologic observations, we interpret that the backstop was generated due to the large age differences of accreted material resulting from an inferred hiatus in subduction between ∼13 and 6 Ma. The time-dependent processes such as the igneous activity in middle Miocene further contribute to the development of the backstop. A ridge structure beneath the forearc basin located trenchward of this backstop and running roughly parallel to it appears to reflect activity on an ancient splay fault. The strike of the ancient splay fault runs parallel to the backstop identified in this study and oblique to the current trench. This geometry suggests that location and mechanical behavior of this splay fault system is influenced by the backstop, and its distribution could be related to the coseismic rupture area.ISSN:0012-821XISSN:1385-013

Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System

Benzo[a]pyrene (BaP), a major environmental pollutant, activates aryl hydrocarbon receptor (AHR), induces its cytoplasmic-to-nuclear translocation and upregulates the production of cytochrome P450 1A1 (CYP1A1), a xenobiotic metabolizing enzyme which metabolize BaP. The BaP-AHR-CYP1A1 axis generates reactive oxygen species (ROS) and induces proinflammatory cytokines. Although the anti-inflammatory phytochemical baicalein (BAI) is known to inhibit the BaP-AHR-mediated CYP1A1 expression, its subcellular signaling remains elusive. In this study, normal human epidermal keratinocytes and HaCaT keratinocytes were treated with BAI, BaP, or BAI + BaP, and assessed for the CYP1A1 expression, antioxidative pathways, ROS generation, and proinflammatory cytokine expressions. BAI and BAI-containing herbal medicine Wogon and Oren-gedoku-to could inhibit the BaP-induced CYP1A1 expression. In addition, BAI activated antioxidative system nuclear factor-erythroid 2-related factor-2 (NRF2) and heme oxygenase 1 (HMOX1), leading the reduction of BaP-induced ROS production. The BaP-induced IL1A and IL1B was also downregulated by BAI. BAI inhibited the phosphorylation of Src, a component of AHR cytoplasmic complex, which eventually interfered with the cytoplasmic-to-nuclear translocation of AHR. These results indicate that BAI and BAI-containing herbal drugs may be useful for inhibiting the toxic effects of BaP via dual AHR-CYP1A1-inhibiting and NRF2-HMOX1-activating activities

Identification of the static backstop and its influence on the evolution of the accretionary prism in the Nankai Trough

To reveal the origin of a backstop and its influence on the evolution of the accretionary prism, we analyzed reflection seismic data acquired in the Nankai Trough off the Kii Peninsula. The deformation features of the forearc basin sequence show that the landward accretionary prism close to the coast was not deformed after the development of the forearc basin about 2–4 Ma. The surface of the landward prism can be identified as strong amplitude reflector, indicating that the landward prism has higher seismic velocity. Therefore, the landward accretionary prism inferred to be of higher strength constitutes a static backstop. Based on seismic and geologic observations, we interpret that the backstop was generated due to the large age differences of accreted material resulting from an inferred hiatus in subduction between ∼13 and 6 Ma. The time-dependent processes such as the igneous activity in middle Miocene further contribute to the development of the backstop. A ridge structure beneath the forearc basin located trenchward of this backstop and running roughly parallel to it appears to reflect activity on an ancient splay fault. The strike of the ancient splay fault runs parallel to the backstop identified in this study and oblique to the current trench. This geometry suggests that location and mechanical behavior of this splay fault system is influenced by the backstop, and its distribution could be related to the coseismic rupture area

Aryl Hydrocarbon Receptor and Dioxin-Related Health Hazards—Lessons from Yusho

Poisoning by high concentrations of dioxin and its related compounds manifests variable toxic symptoms such as general malaise, chloracne, hyperpigmentation, sputum and cough, paresthesia or numbness of the extremities, hypertriglyceridemia, perinatal abnormalities, and elevated risks of cancer-related mortality. Such health hazards are observed in patients with Yusho (oil disease in Japanese) who had consumed rice bran oil highly contaminated with 2,3,4,7,8-pentachlorodibenzofuran, polychlorinated biphenyls, and polychlorinated quaterphenyls in 1968. The blood concentrations of these congeners in patients with Yusho remain extremely elevated 50 years after onset. Dioxins exert their toxicity via aryl hydrocarbon receptor (AHR) through the generation of reactive oxygen species (ROS). In this review article, we discuss the pathogenic implication of AHR in dioxin-induced health hazards. We also mention the potential therapeutic use of herbal drugs targeting AHR and ROS in patients with Yusho