Natália Pereira da Silva Araújo

Paracetamol (APAP) overdose is the leading cause of drug-induced liver injury, leading to acute liver failure. However, the role of concurrent acute or chronic ethanol ingestion in this context requires further clarification. In this study, we investigated the effects of acute and chronic ethanol ingestion on APAP-induced hepatotoxicity. Male C57BL/6 mice were randomly allocated into four groups: control (C; water 2×/day for 7 days); APAP (single dose of APAP, 500 mg/kg); acute ethanol (AE; a single ethanol dose—10 mL/kg, and one hour later an overdose of APAP—500 mg/kg); chronic ethanol (CE; ethanol—10 mL/kg, 2×/day for 7 days; and on the last day, an overdose of APAP—500 mg/kg). The results showed that AE induced heightened liver damage, increased necrotic area, and elevated levels of ALT, AST, TBARS, and oxidized glutathione compared to the control group. The AE group exhibited diminished glutathione availability and elevated CYP2E1 levels compared to the other groups. CE maintained a hepatic profile similar to that of the control group in terms of necrosis index, ALT and AST levels, GSH/GSSG ratio, and CYP2E1 activity, along with the upregulation of gene expression of the glucuronidation enzyme compared to the APAP group. Proteomic analysis revealed that the AE protein profile closely resembled that of the APAP group, whereas the C and CE groups were clustered together. In conclusion, ethanol consumption differentially modulated APAP overdose-induced liver damage. Acute consumption exacerbated hepatotoxicity, similar to an APAP overdose alone, whereas chronic consumption appeared to mitigate this injury, at least within the parameters assessed in this study.

Cigarette smoking throughout life causes serious health issues in the lungs. The electronic cigarette (E‐Cig) use increased, since it was first introduced in the world. This research work compared the short‐term exposure consequences to e‐cigarette vapor and cigarette smoke in male mice. Forty‐five C57BL/6 mice were randomized into control (C) in an ambient air exposition cigarette smoke (CS) and aerosol electronic cigarette (EC), both were exposed to 120 puffs, 3 times/day during five days. Then, in the experimental protocol, the euthanized mice had their tissues removed for analysis. Our study showed that CS and EC resulted in higher cell influx into the airways, and an increase in macrophage counts in CS (209.25 ± 7.41) and EC (220.32 ± 8.15) when compared to C (108.40 ± 4.49) (p < 0.0001). The CS (1.92 ± 0.23) displayed a higher pulmonary lipid peroxidation as opposed to C (0.93 ± 0.06) and EC (1.23 ± 0.17) (p < 0.05). The EC (282.30 ± 25.68) and CS (368.50 ± 38.05) promoted increased levels of interleukin 17 when compared to C (177.20 ± 10.49) (p < 0.05). The EC developed shifts in lung histoarchitecture, characterized by a higher volume density in the alveolar air space (60.21; 55.00‐65.83) related to C (51.25; 18.75‐68.75) and CS (50.26; 43.75‐62.08) (p =0.002). The EC (185.6 ± 9.01) presented a higher respiratory rate related to CS (133.6 ± 10.2) (p < 0.002). Therefore, our findings demonstrated that the short‐term exposure to e‐cig promoted more acute inflammation comparing to cigarette smoke in the ventilatory parameters of the animals.

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.

Cigarette smoke is highly toxic, and it can promote increased production of reactive species and inflammatory response and leads to liver diseases. Quercetin is a flavonoid that displays antioxidant and anti‐inflammatory activities in liver diseases. This study aimed at evaluating the protective effects of quercetin on livers from mice exposed to long‐term cigarette smoke exposure. Male C57BL/6 mice were divided into five groups: control (CG), vehicle (VG), quercetin (QG), cigarette smoke (CSG), quercetin, and cigarette smoke (QCSG). CSG and QCSG were exposed to cigarette smoke for sixty consecutive days; at the end of the exposures, all animals were euthanized. Mice that received quercetin daily and were exposed to cigarette smoke showed a reduced influx of inflammatory cells, oxidative stress, inflammatory reaction, and histopathological changes in the liver, compared to CSG. These results suggest that quercetin may be an effective adjuvant for treating damage to the liver due to cigarette smoke exposure.

In addition to the risk of developing ventilator-induced lung injury, patients with ARDS are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia. Alterations of endogenous surfactant system participate in the pulmonary dysfunction observed in ARDS. Administration of exogenous surfactant could have protective effects during hyperoxia. Male BALB/c mice (8–10 weeks), a strain highly sensitive to hyperoxia, received the exogenous surfactant-containing protein SP-B and SP-C by intranasal instillation 12 h before starting 24 h of exposure to hyperoxia in an inhalation chamber and were compared to mice receiving hyperoxia alone and to controls subjected to normoxia. Compared to the hyperoxia group, the administration of exogenous surfactant was able to reduce lung inflammation through a reduction in the influx of neutrophils and inflammatory biomarkers such as TNF, IL-17, and HMGB1 expression. The antioxidant activity prevented oxidative damage by reducing lipid peroxidation and protein carbonylation and increasing superoxide dismutase activity when compared to the hyperoxia group. Our results offer new perspectives on the effects and the mechanism of exogenous surfactant in protecting the airway and lungs, in oxygen-rich lung microenvironment, against oxidative damage and aggravation of acute inflammation induced by hyperoxia.