N-acetylcysteine modulates redox imbalance and inflammation in macrophages and mice exposed to formaldehyde.

This study aimed to evaluate the protective role of N-acetylcysteine (NAC) in cells and mice exposed to formaldehyde. For the in vitro study, J774A.1 macrophages cells were incubated for 8, 16 and 24 h with formaldehyde or NAC to assess cell viability and reactive oxygen species (ROS). In the in vivo study, C57BL/6 mice (n = 48) were divided into 6 groups: control (CG), vehicle (VG) that received saline by orogastric gavage, a group exposed to formaldehyde 1% (FG) and formaldehyde exposed groups that received NAC at doses of 100, 150 and 200 mg/Kg (FN100, FN150 and FN200) for a period of 5 days. In vitro, formaldehyde promoted a decrease in cell viability and increased ROS, while NAC reduced formaldehyde-induced ROS production. Animals exposed to formaldehyde presented higher leukocyte counts in the blood and in the bronchoalveolar lavage fluid, and promoted secretion of inflammatory markers IL-6, IL-15, and IL-10. The exposure to formaldehyde also promoted redox imbalance and oxidative damage characterized by increased activities of superoxide dismutase, catalase, decreased GSH/GSSG ratio, as well as it increased levels of protein carbonyls and lipid peroxidation. NAC administration after formaldehyde exposure attenuated oxidative stress markers, secretion of inflammatory mediators and lung inflammation. In conclusion, both in in vitro and in vivo models, NAC administration exerted protective effects, which modulated the inflammatory response and redox imbalance, thus preventing the development airway injury induced by formaldehyde exposure.

Effects of a lycopene-layered double hydroxide composite administration in cells and lungs of adult mice.

Lycopene is a natural compound with one of the highest antioxidant activities. Its consumption is associated with lower risks in lung cancer and chronic obstructive pulmonary disease, for example. Experimentally, a murine model demonstrated the ingestion of lycopene, which reduced the damage in lungs caused by cigarette smoke. Since lycopene is highly hydrophobic, its formulations in supplements and preparations for laboratory assays are based on oils, additionally, bioavailavility is low. We developed a lycopene layered double hydroxide (Lyc-LDH) composite, which is capable of transporting lycopene aqueous media. Our objective was to evaluate the cytotoxicity of Lyc-LDH and the intra-cellular production of reactive oxygen species (ROS) in J774A.1 cells. Also, in vivo assays were conducted with 50 male C57BL/6 mice intranasally treated with Lyc-LDH 10 mg/kg (LG10), Lyc-LDH 25 mg/kg (LG25) and Lyc-LDH 50 mg/kg (LG50) during five days compared against a vehicle (VG) and control (CG) group. The blood, bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed. The results revealed that Lyc-LDH composite attenuated intracellular ROS production stimulated with lipopolysacharide. In BALF, the highest doses of Lyc-LDH (LG25 and LG50) promoted influx of macrophages, lymphocytes, neutrophils and eosinophils compared to CG and VG. Also, LG50 increased the levels of IL-6 and IL-13, and promoted the redox imbalance in the pulmonary tissue. On the contrary, low concentrations did not produce significative effects. In conclusion, our results suggest that intranasal administration of high concentrations of Lyc-LDH induces inflammation as well as redox status changes in the lungs of healthy mice, however, results with low concentrations open a promising way to study LDH composites as vehicles for intranasal administration of antioxidant coadjuvants.

Long-term e-cigarette aerosol exposure causes pulmonary emphysema in adult female and male mice.

This study aimed to evaluate long-term exposure to conventional cigarette smoke (CC) and electronic cigarette (EC) aerosol in adult male and female C57BL/6 mice. Forty-eight C57BL/6 mice were used, male (n = 24) and female (n = 24), both were divided into three groups: control, CC and EC. The CC and EC groups were exposed to cigarette smoke or electronic cigarette aerosol, respectively, 3 times a day for 60 consecutive days. Afterwards, they were maintained for 60 days without exposure to cigarettes or electronic cigarette aerosol. Both cigarettes promoted an influx of inflammatory cells to the lung in males and females. All animals exposed to CC and EC showed an increase in lipid peroxidation and protein oxidation. There was an increase of IL-6 in males and females exposed to EC. The IL-13 levels were higher in the females exposed to EC and CC. Both sexes exposed to EC and CC presented tissue damage characterized by septal destruction and increased alveolar spaces compared to control. Our results demonstrated that exposure to CC and EC induced pulmonary emphysema in both sexes, and females seem to be more susceptible to EC.

Exogenous surfactant reduces inflammation and redox imbalance in rats under prone or supine mechanical ventilation.

Mechanical ventilation (MV) is a lifesaving therapy for patients with acute or chronic respiratory failure. Despite, it can also cause lung injury by inducing or worsening inflammatory responses and oxidative stress. Several clinical approaches have protective effects on the lungs, including the prone position and exogenous surfactant; however, few studies have evaluated the association between the two strategies, especially in individuals without previous lung injury. We tested the hypothesis that the effects of the homogenization in lung aeration caused by the prone position in association with the anti-inflammatory properties of exogenous surfactant pre-treatment could have a cumulative protective effect against ventilator-induced lung injury. Therefore, Wistar rats were divided into four experimental groups: Mechanical Ventilation in Supine Position (MVSP), Mechanical Ventilation in Prone position (MVPP), Mechanical Ventilation in Supine Position + surfactant (MVSPS), and Mechanical Ventilation in Prone Position + Surfactant (MVPPS). The intranasal instillation of a porcine surfactant (Curosurf®) was performed in the animals of MVSPS and MVPPS 1 h before the MV, all the rats were subjected to MV for 1 h. The prone position in association with surfactant decreased mRNA expression levels of pro-inflammatory cytokines in ventilated animals compared to the supine position; in addition, the NfκB was lower in MVPP, MVSPS and MVPPS when compared to MVSP. However, it had no effects on oxidative stress caused by MV. Pre-treatment with exogenous surfactant was more efficient in promoting lung protection than the prone position, as it also reduced oxidative damage in the lung parenchyma. Nevertheless, the surfactant did not cause additional improvements in most parameters that were also improved by the prone position. Our results indicate that the pre-treatment with exogenous surfactant, regardless of the position adopted in mechanical ventilation, preserves the original lung histoarchitecture, reduces redox imbalance, and reduces acute inflammatory responses caused by mechanical ventilation in healthy adult Wistar rats.

The deleterious impact of exposure to different inhaled anesthetics is time dependent.

In this study, the effects of exposure to isoflurane, sevoflurane and desflurane on the oxidative response and inflammation at different times was analyzed in the lungs of adult C57BL/6 mice. 120 animals were divided into 3 groups (n = 40): Isoflurane (ISO), Sevoflurane (SEV) and Desflurane (DES) and exposed to these anesthetics for 1 h (n = 10), 2 h (n = 10) and 3 h (n = 10), at a minimum alveolar concentration (MAC) equal to 1. The control group (CG) (n = 10) was exposed to ambient air. 24 h after the experimental protocol, the animals were euthanized and the bronchoalveolar lavage fluid (BALF), blood and lung tissue samples were collected. In the BALF, animals exposed to isoflurane for 2 h and 3 h showed a greater influx of leukocytes, especially macrophages compared to the CG. The ISO3h had lower leukocyte counts in the peripheral blood compared to CG, ISO1h and ISO2h. There was an increase in CCL-2 levels in the ISO3h compared to the CG. Superoxide dismutase activity was higher in ISO1h compared to CG. The activity of catalase was higher in the ISO1h and ISO2h compared to the CG. The lipid peroxidation, as well as carbonylated protein were higher in the ISO3h compared to the CG (p < 0.05). Similar results were observed in the exposure of SEV and DES compared to inflammation and redox imbalance in different periods. This study demonstrated that time is a determinant to promote a local and systemic inflammatory response to different inhalational anesthetics in a healthy murine model.

Quercetin Improves Pulmonary Function and Prevents Emphysema Caused by Exposure to Cigarette Smoke in Male Mice.

Chronic obstructive pulmonary disease (COPD) is the major cause of morbidity and mortality worldwide, and cigarette smoke is a key factor in the development of COPD. Thus, the development of effective therapies to prevent the advancement of COPD has become increasingly essential. We hypothesized that quercetin protects lungs in mice exposed to long-term cigarette smoke. Thirty-five C57BL/6 mice were exposed to cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 10 mg/kg/day of quercetin via orogastric gavage. After the experimental protocol, the animals were euthanized and samples were collected for histopathological, antioxidant defense, oxidative stress and inflammatory analysis. The animals exposed to cigarette smoke showed an increase in respiratory rate and hematological parameters, cell influx into the airways, oxidative damage and inflammatory mediators, besides presenting with alterations in the pulmonary histoarchitecture. The animals receiving 10 mg/kg/day of quercetin that were exposed to cigarette smoke presented a reduction in cellular influx, less oxidative damage, reduction in cytokine levels, improvement in the histological pattern and improvement in pulmonary emphysema compared to the group that was only exposed to cigarette smoke. These results suggest that quercetin may be an agent in preventing pulmonary emphysema induced by cigarette smoke.

Lycopene Ameliorates Liver Inflammation and Redox Status in Mice Exposed to Long-Term Cigarette Smoke.

Cigarette smoke (CS) is the major cause of preventable death worldwide, and it can also cause damage to extrapulmonary organs, such as the liver, mainly due the generation of reactive oxygen species (ROS). The liver is an essential organ for human survival since it is mainly responsible for the body metabolism and among other things and it is the place where many endogenous and exogenous substances undergo biological transformation. Lycopene is a nonprovitamin A carotenoid found in red fruits and vegetables, and its role as a potent antioxidant is well known. In this study, we hypothesized that lycopene could protect mouse liver against long-term CS exposure. Thirty C57BL/6 mice were exposed to twelve cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 25 mg/kg/day or 50 mg/kg/day of lycopene via orogastric gavage. After euthanasia, the hepatic tissue was collected for histopathological, antioxidant defense, oxidative stress, inflammatory, and collagen deposition analysis. Our analysis demonstrated that lycopene results in a suitable outcome to ameliorate the pathological changes, inflammatory and antioxidant profile in a mouse model of long-term CS exposure, and collagen accumulation in the hepatic extracellular matrix. This study demonstrates for the first time that supplementation of lycopene can be a possible pharmacological tool for the treatment of hepatic damage caused by exposure to long-term CS.