Urban air pollution induces alterations in redox metabolism and mitochondrial dysfunction in mice brain cortex

Abstract

Previous reports indicate that the central nervous system (CNS) is a target of airpollution, causing tissue damage and functional alterations. Oxidative stress andneuroinflammation 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 braincortex, focusing on oxidative stress markers, and mitochondrial function. Male 8-week-oldBALB/c mice were exposed to filtered air (FA, control) or urban air (UA) inside whole-bodyexposure chambers, located in a highly polluted area of Buenos Aires city, for up to 4 weeks.Glutathione levels, assessed as GSH/GSSG ratio, were decreased after 1 and 2 weeks ofexposure to UA (45% and 25% respectively vs. FA; p<0.05). A 38% increase in lipidperoxidation was found after 1 week of UA exposure (p<0.05). Regarding protein oxidation,carbonyl content was significantly increased at week 2 in UA-exposed mice, compared toFA-group, and an even higher increment was found after 4 weeks of exposure (week 2: 40%p<0.05, week 4: 54% p<0.001). NADPH oxidase (NOX) and glutathione peroxidase (GPx)activities were augmented at all the studied time points, while superoxide dismutase (Cu,Zn-SOD cytosolic isoform) and glutathione reductase (GR) activities were increased only after 4weeks of UA exposure (p<0.05).The increased NOX activity was accompanied with higherexpression levels of NOX2 regulatory subunit p47phox, and NOX4 (p<0.05). Also, UA miceshowed impaired mitochondrial function due to a 50% reduction in O2 consumption in activestate respiration (p<0.05), a 29% decrease in mitochondrial inner membrane potential(p<0.05), a 65% decrease in ATP production rate (p<0.01) and a 30% increase in H2O2production (p<0.01). Moreover, respiratory complexes I-III and II-III activities were decreasedin UA group (30% and 36% respectively vs. FA; p<0.05). UA exposed mice showedalterations in mitochondrial function, increased oxidant production evidenced by NOXactivation, macromolecules damage and the onset of the enzymatic antioxidant system.These data indicate that oxidative stress and impaired mitochondrial function may play a keyrole in CNS damage mechanisms triggered by air pollution.