Details

Autor(en) / Beteiligte

• Calabró, Valeria
• Garcés, Mariana
• Cáceres, Lourdes
• Magnani, Natalia D.
• Marchini, Timoteo
• Freire, Agustina
• Vico, Tamara
• Martinefski, Manuela
• Vanasco, Virginia
• Tripodi, Valeria
• Berra, Alejandro
• Alvarez, Silvia
• Evelson, Pablo

Titel

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

Ist Teil von

• Archives of biochemistry and biophysics, 2021-06, Vol.704, p.108875-108875, Article 108875

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 brain cortex, 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. Glutathione levels, assessed as GSH/GSSG ratio, were decreased after 1 and 2 weeks of exposure to UA (45% and 25% respectively vs. FA; p < 0.05). A 38% increase in lipid peroxidation 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 to FA-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 4 weeks of UA exposure (p < 0.05). The increased NOX activity was accompanied with higher expression levels of NOX2 regulatory subunit p47phox, and NOX4 (p < 0.05). Also, UA mice showed impaired mitochondrial function due to a 50% reduction in O2 consumption in active state 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 H2O2 production (p < 0.01). Moreover, respiratory complexes I-III and II-III activities were decreased in UA group (30% and 36% respectively vs. FA; p < 0.05). UA exposed mice showed alterations in mitochondrial function, increased oxidant production evidenced by NOX activation, macromolecules damage and the onset of the enzymatic antioxidant system. These data indicate that oxidative stress and impaired mitochondrial function may play a key role in CNS damage mechanisms triggered by air pollution. [Display omitted] •Exposure to urban air induces oxidative stress characterized by macromolecules damage and an overwhelmed antioxidant defense system.•NADPH oxidases are relevant sources of superoxide anion (O2.•-) and H2O2.•Urban air impairs mitochondrial function characterized by decreased respiratory control ratio and ATP mismanagement.•Altered redox metabolism and mitochondrial function are key mechanisms in CNS damage triggered by air pollution.