Co-exposure to inhaled tungsten particles and low-dose gamma rays: neurotoxicological outcome in rats

Throughout their lives, individuals are exposed to various pollutants, potentially including co-exposure to radiological and chemical stressors. Yet, existing literature about these combinations is scarce. We selected tungsten and ionizing radiations. Tungsten is an emerging contaminant present as aerosolized particles in several scenarios, potentially concurrently with low-dose irradiation, causing a co-exposure. The cerebral toxicity of this co-exposure was studied after 24 h and 28 days in the frontal cortex and olfactory bulb of male Sprague-Dawley rats exposed to gamma irradiation (50 mGy) and/or inhalation of tungsten particles aerosol (80 mg.m^-3). Co-exposure triggered significant effects more frequently than single stressors. Observed effects were associated with oxidative status changes, notably via NRF2 nuclear translocation, and modulation of pro-inflammatory cytokines (IL1β, TNFα). A reduction in cortical microglial density suggested a cellular migration toward the olfactory bulb and could contribute to the occurrence of a neuronal suffering phenotype. The effects persisted at 28 days and were brain structure specific. Biodistribution of tungsten showed that both local and systemic effects might be involved. Our results suggest interaction between our stressors, causing cerebral toxicity, and prove the importance of multi-stressor studies to improve risks evaluation in toxicology and radiation protection, as single stressors might wrongly be deemed safe.