Acute exposure to C60 fullerene damages pulmonary mitochondrial function and mechanics.

C60 fullerene (C60) nanoparticles, a nanomaterial widely used in technology, can offer risks to humans, overcome biological barriers, and deposit onto the lungs. However, data on its putative pulmonary burden are scanty. Recently, the C60 interaction with mitochondria has been described in vitro and in vivo. We hypothesized that C60 impairs lung mechanics and mitochondrial function. Thirty-five male BALB/c mice were randomly divided into two groups intratracheally instilled with vehicle (0.9% NaCl + 1% Tween 80, CTRL) or C60 (1.0 mg/kg, FUL). Twenty-four hours after exposure, 15 FUL and 8 CTRL mice were anesthetized, paralyzed, and mechanically ventilated for the determination of lung mechanics. After euthanasia, the lungs were removed en bloc at end-expiration for histological processing. Lung tissue elastance and viscance were augmented in FUL group. Increased inflammatory cell number, alveolar collapse, septal thickening, and pulmonary edema were detected. In other six FUL and six CTRL mice, mitochondria expressed reduction in state 1 respiration [FUL = 3.0 ± 1.14 vs. CTRL = 4.46 ± 0.9 (SEM) nmol O2/min/mg protein, p = 0.0210], ATP production (FUL = 122.6 ± 18 vs. CTRL = 154.5 ± 14 µmol/100 µg protein, p = 0.0340), and higher oxygen consumption in state 4 [FUL = 12.56 ± 0.9 vs. CTRL = 8.26 ± 0.6], generation of reactive oxygen species (FUL 733.1 ± 169.32 vs. CTRL = 486.39 ± 73.1 nmol/100 µg protein, p = 0.0313) and reason ROS/ATP [FUL = 8.73 ± 2.3 vs. CTRL = 2.99 ± 0.3]. In conclusion, exposure to fullerene C60 impaired pulmonary mechanics and mitochondrial function, increased ROS concentration, and decrease ATP production.

Elastic power but not driving power is the key promoter of ventilator-induced lung injury in experimental acute respiratory distress syndrome.

BACKGROUND: We dissected total power into its primary components to resolve its relative contributions to tissue damage (VILI). We hypothesized that driving power or elastic (dynamic) power offers more precise VILI risk indicators than raw total power. The relative correlations of these three measures of power with VILI-induced histologic changes and injury biomarkers were determined using a rodent model of acute respiratory distress syndrome (ARDS). Herein, we have significantly extended the scope of our previous research. METHODS: Data analyses were performed in male Wistar rats that received endotoxin intratracheally to induce ARDS. After 24 h, they were randomized to 1 h of volume-controlled ventilation with low VT = 6 ml/kg and different PEEP levels (3, 5.5, 7.5, 9.5, and 11 cmH2O). Applied levels of driving power, dynamic power inclusive of PEEP, and total power were correlated with VILI indicators [lung histology and biological markers associated with inflammation (interleukin-6), alveolar stretch (amphiregulin), and epithelial (club cell protein (CC)-16) and endothelial (intercellular adhesion molecule-1) cell damage in lung tissue]. RESULTS: Driving power was higher at PEEP-11 than other PEEP levels. Dynamic power and total power increased progressively from PEEP-5.5 and PEEP-7.5, respectively, to PEEP-11. Driving power, dynamic power, and total power each correlated with the majority of VILI indicators. However, when correlations were performed from PEEP-3 to PEEP-9.5, no relationships were observed between driving power and VILI indicators, whereas dynamic power and total power remained well correlated with CC-16 expression, alveolar collapse, and lung hyperinflation. CONCLUSIONS: In this mild-moderate ARDS model, dynamic power, not driving power alone, emerged as the key promoter of VILI. Moreover, hazards from driving power were conditioned by the requirement to pass a tidal stress threshold. When estimating VILI hazard from repeated mechanical strains, PEEP must not be disregarded as a major target for modification.

Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury.

We investigated the effects of acute hypercapnic acidosis and buffered hypercapnia on lung inflammation and apoptosis in experimental acute lung injury (ALI). Twenty-four hours after paraquat injection, 28 Wistar rats were randomized into four groups (n=7/group): (1) normocapnia (NC, PaCO2=35-45 mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70 mmHg), ventilated with 5%CO2+21%O2+balancedN2; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO2+21%O2+balancedN2 and treated with sodium bicarbonate (8.4%). The remaining seven animals were not mechanically ventilated (NV). The mRNA expression of interleukin (IL)-6 (p=0.003), IL-1ß (p<0.001), and type III procollagen (PCIII) (p=0.001) in lung tissue was more reduced in the HC group in comparison with NC, with no significant differences between HC and BHC. Lung and kidney cell apoptosis was reduced in HC and BHC in comparison with NC and NV. In conclusion, in this experimental ALI model, hypercapnia, regardless of acidosis, reduced lung inflammation and lung and kidney cell apoptosis.