Chronic exposure to urban air pollution in Buenos Aires city induces oxidative stress and inflammation in mice olfactory bulb

Abstract

Previous reports indicate that the central nervous system (CNS) is a target of air pollution, causing tissue damage and functional alterations. Oxidative stress and neuroinflammation have been pointed out as possible mechanisms mediating these effects. The aim of this work was to study the chronic effects of urban air pollution on mice olfactory bulb (OB), focusing on oxidative stress markers, and mitochondrial function. Male 8-week-old BALB/c mice were exposed to filtered air (FA, control) or urban air (UA) inside whole-body exposure chambers, located in a highly polluted area of Buenos Aires city, for up to 4 weeks. OB tissue redox status, assessed as GSH/GSSG ratio, was decreased by 60% after 4 weeks of exposure to UA. Superoxide dismutase (SOD) activity showed a 40% decrease after 1 week of UA exposure (p <0.05), while SOD and glutathione reductase (GR) activities were increased after 4 weeks, compared to FA (p<0.05). Also, UA mice showed impaired mitochondrial function due to a 60% increase of H2O2 production after 4 weeks (p<0.01). Moreover, protein expression of NOX4 and NOX2 (p47phox regulatory subunit), both NADPH oxidases isoforms commonly found increased in inflammatory processes, were found augmented in UA group, after 1 and 4 weeks, respectively, compared to FA (p <0.05). After 4 weeks of UA exposure, increased GFAP expression levels showed reactive astrocytes in OB, probably associated with the altered olfactory function observed by a behavioral test, in UA compared to FA mice (p<0.05). Taken together, UA exposure showed an increase in oxidants production and an inflammatory response that lead to OB oxidative stress and impaired mitochondrial function, and consequently an olfactory discrimination alteration. These data indicate that oxidative stress and impaired mitochondrial function may play a key role in CNS damage mechanisms triggered by air pollution.