Dual TNFα-induced effects on NRF2 mediated antioxidant defence in astrocyte-rich cultures: role of protein kinase activation

Tumor necrosis factor-α (TNFα) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNFα on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of γGCL (γGCL-C and γGCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNFα. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNFα increased GSH, γGCL activity, the protein levels of γGCL-M, γGCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3β further enhanced transcription. In contrast treatment with TNFα for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNFα. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3β, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNFα (24 h treatment) protected the cells from oxidative stress through elevated γGCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer’s disease, the effect of TNFα is detrimental.Fil: Correa, Fernando Gabriel. University Goteborg; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mallard, Carina. University Goteborg; SueciaFil: Nilsson, Michael. University Goteborg; SueciaFil: Sandberg, Mats. University Goteborg; Sueci

Radiological dose rates to marine fish from the Fukushima Daiichi Accident: the first three years across the North Pacific.

A more complete record is emerging of radionuclide measurements in fish tissue, sediment, and seawater samples from near the Fukushima Daiichi Nuclear Power Plant (FDNPP) and across the Pacific Ocean. Our analysis of publicly available data indicates the dose rates to the most impacted fish species near the FDNPP (median 1.1 mGy d–1, 2012–2014 data) have remained above benchmark levels for potential dose effects at least three years longer than was indicated by previous, data-limited evaluations. Dose rates from 134,137Cs were highest in demersal species with sediment-associated food chains and feeding behaviors. In addition to 134,137Cs, the radionuclide 90Sr was estimated to contribute up to approximately one-half of the total 2013 dose rate to fish near the FDNPP. Mesopelagic fish 100–200 km east of the FDNPP, coastal fish in the Aleutian Islands (3300 km), and trans-Pacific migratory species all had increased dose rates as a consequence of the FDNPP accident, but their total dose rates remained dominated by background radionuclides. A hypothetical human consumer of 50 kg of fish, gathered 3 km from the FDNPP in 2013, would have received a total committed effective dose of approximately 0.95 mSv a–1 from combined FDNPP and ambient radionuclides, of which 0.13 mSv a–1 (14%) was solely from the FDNPP radionuclides and below the 1 mSv a–1 benchmark for public exposure. © 2014 American Chemical Societ

Recent developments in the modelling of radionuclide uptake, radiation dose and effects in wildlife

Of the ~600 scientific publications on the Fukushima event, more than 80% relate to themes of transport of radionuclides in environmental media, transfer to wildlife and foodstuffs, and dose to environmental receptors. This focus reflects a continued need for development and harmonisation of radiological modelling approaches such as has been underway through recent IAEA and ICRP initiatives (e.g. EMRAS I and II, MODARIA). Key developments in improving the understanding of uptake of radionuclides in wildlife include establishing the Wildlife Transfer Parameter Database and related IAEA handbook on transfer to wildlife. These sources provide access to a comprehensive collection of transfer parameters, including input from Australian sources (www.wildlifetransferdatabase.org). Key improvements were highlighted in a recent Journal of Environmental Radioactivity special issue (Vol. 121). Dose modelling for wildlife continues to be challenged by the high diversity of biotic types (plankton to whales) and the breadth of exposure scenarios in diverse ecosystems. Modelling codes (e.g. ERICA Tool, RESRAD-Biota) are undergoing updates of their transfer parameters, improvement of capabilities such as probabilistic analysis (e.g. Monte Carlo), and harmonization of approaches through IAEA model testing exercises (e.g., Little Forest Burial Ground biota dose modelling assessment). A recent development has been the use of voxel dosimetry approaches which build on the standard simplified ellipsoid approach by modelling the absorbed doses in individual organs. Recent improvements in defining dose effects to environmental receptors have focused on updating the FREDERICA Radiation Effects Database. The more comprehensive data have allowed for the updating/development of new Species Sensitivity Distributions that better support the benchmark values for potential dose effects, and for improving estimation of population effects (rather than individuals) upon which the environmental protection strategies are based

Ensuring robust radiological risk assessment for wildlife: insights from the International Atomic Energy Agency EMRAS and MODARIA programmes

In response to changing international recommendations and national requirements, a number of assessment approaches, and associated tools and models, have been developed over the last circa 20 years to assess radiological risk to wildlife. In this paper, we summarise international intercomparison exercises and scenario applications of available radiological assessment models for wildlife to aid future model users and those such as regulators who interpret assessments. Through our studies, we have assessed the fitness for purpose of various models and tools, identified the major sources of uncertainty and made recommendations on how the models and tools can best be applied to suit the purposes of an assessment. We conclude that the commonly used tiered or graded assessment tools are generally fit for purpose for conducting screening-level assessments of radiological impacts to wildlife. Radiological protection of the environment (or wildlife) is still a relatively new development within the overall system of radiation protection and environmental assessment approaches are continuing to develop. Given that some new/developing approaches differ considerably from the more established models/tools and there is an increasing international interest in developing approaches that support the effective regulation of multiple stressors (including radiation), we recommend the continuation of coordinated international programmes for model development, intercomparison and scenario testing

Ensuring robust radiological risk assessment for wildlife: insights from the International Atomic Energy Agency EMRAS and MODARIA programmes

In response to changing international recommendations and national requirements, a number of assessment approaches, and associated tools and models, have been developed over the last circa 20 years to assess radiological risk to wildlife. In this paper, we summarise international intercomparison exercises and scenario applications of available radiological assessment models for wildlife to aid future model users and those such as regulators who interpret assessments. Through our studies, we have assessed the fitness for purpose of various models and tools, identified the major sources of uncertainty and made recommendations on how the models and tools can best be applied to suit the purposes of an assessment. We conclude that the commonly used tiered or graded assessment tools are generally fit for purpose for conducting screening-level assessments of radiological impacts to wildlife. Radiological protection of the environment (or wildlife) is still a relatively new development within the overall system of radiation protection and environmental assessment approaches are continuing to develop. Given that some new/developing approaches differ considerably from the more established models/tools and there is an increasing international interest in developing approaches that support the effective regulation of multiple stressors (including radiation), we recommend the continuation of coordinated international programmes for model development, intercomparison and scenario testing