Sevoflurane inhibits ferroptosis: A new mechanism to explain its protective role against lipopolysaccharide-induced acute lung injury.
TL;DR: Sevoflurane (Sev) has been shown to protect mice from lung injury caused by LPS stimulation, including extenuating lung histological damage, pulmonary edema and pulmonary vascular permeability, and the content of inflammatory factors in Bronchoalveolar lavage fluid (BALF).
About: This article is published in Life Sciences.The article was published on 2021-06-15. It has received 24 citations till now. The article focuses on the topics: Lung injury.
Citations
More filters
TL;DR: In this article , the role of STAT6 in the pathophysiological process of acute lung injury (ALI) was investigated and it was found that STAT6 negatively regulates ferroptosis through competitively binding with CREB-binding protein (CBP), which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression.
Abstract: Compelling evidences have revealed the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI), but its modulation is not clear. Here, we identified that STAT6 acted as a critical regulator of epithelium ferroptosis during ALI. Firstly, STAT6 expression and activity were increased in the ALI mice models caused by crystalline silica (CS), LPS and X-ray exposure. Followed by confirming the contribution of ferroptosis in the above ALI with ferrostatin-1 and deferoxamine intervention, bioinformatic analyses revealed that STAT6 expression was negatively correlated with ferroptosis. Consistently, lung epithelium-specific depletion of STAT6 in mice or STAT6 knockdown in cultured epithelial cells exacerbated ferroptosis in the above ALI. While overexpression of STAT6 in lung epithelial cells attenuated the ferroptosis. Mechanistically, SLC7A11 is a typical ferroptosis-related gene and negatively regulated by P53. CREB-binding protein (CBP) is a critical acetyltransferase of P53 acetylation, showing valuable regulation on targets' transcription. Herein, we found that STAT6 negatively regulates ferroptosis through competitively binding with CBP, which inhibits P53 acetylation and transcriptionally restores SLC7A11 expression. Finally, pulmonary-specific STAT6 overexpression decreased the ferroptosis and attenuated CS and LPS induced lung injury. Our findings revealed that STAT6 is a pivotal regulator of ferroptosis, which may be a potential therapeutic target for the treatment of acute lung injury.
19 citations
TL;DR: In this article, the role of ferroptosis in the pathogenesis of acute lung injury and its therapeutic potential in ALI was reviewed and its role in the development was discussed.
Abstract: Acute lung injury (ALI), a common and critical illness with high morbidity and mortality, is caused by multiple causes. It has been confirmed that oxidative stress plays an important role in the development of ALI. Ferroptosis, a newly discovered programmed cell death in 2012, is characterized by iron-dependent lipid peroxidation and involved in many diseases. To date, compelling evidence reveals the emerging role of ferroptosis in the pathophysiological process of ALI. Here, we review the role of ferroptosis in the pathogenesis of ALI and its therapeutic potential in ALI.
17 citations
TL;DR: The basic characteristics of ferroptosis, its regulation, as well as the relationship between ferroPTosis and chronic diseases such as cancer, nervous system diseases, metabolic diseases, and inflammatory bowel diseases are summarized.
Abstract: Ferroptosis, which has been widely associated with many diseases, is an iron-dependent regulated cell death characterized by intracellular lipid peroxide accumulation. It exhibits morphological, biochemical, and genetic characteristics that are unique in comparison to other types of cell death. The course of ferroptosis can be accurately regulated by the metabolism of iron, lipids, amino acids, and various signal pathways. In this review, we summarize the basic characteristics of ferroptosis, its regulation, as well as the relationship between ferroptosis and chronic diseases such as cancer, nervous system diseases, metabolic diseases, and inflammatory bowel diseases. Finally, we describe the regulatory effects of food-borne active ingredients on ferroptosis.
15 citations
TL;DR: In this article , the role of ferroptosis in sepsis-induced acute kidney injury (SAKI) has not been studied and whether its downstream mechanism correlates with the Nrf2/HO-1 pathway.
14 citations
TL;DR: In this paper , the role of Cadmium telluride quantum dots (CdTe QDs) in inflammatory responses triggered by nanoparticles (NPs) in macrophages was investigated.
14 citations
References
More filters
TL;DR: The concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes is supported.
Abstract: Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes.
783 citations
TL;DR: Mortality did not decrease between 1994 (when a consensus definition of ALI/ARDS was published) and 2006, and is lower in RCTs than observational studies.
Abstract: Rationale: It is commonly stated that mortality from acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is decreasing.Objectives: To systematically review the literature assessing ARDS mortality over time and to determine patient- and study-level factors independently associated with mortality.Methods: We searched multiple databases (MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL) for prospective observational studies or randomized controlled trials (RCTs) published during the period 1984 to 2006 that enrolled 50 or more patients with ALI/ARDS and reported mortality. We pooled mortality estimates using random-effects meta-analysis and examined mortality trends before and after 1994 (when a consensus definition of ALI/ARDS was published) and factors associated with mortality using meta-regression models.Measurements and Main Results: Of 4,966 studies, 89 met inclusion criteria (53 observational, 36 RCTs). There was a total of 18,900 patients (mean age 51.6 years; 39% female). Overall pooled ...
716 citations
TL;DR: The history of observations consistent with the current definition of ferroptosis, as well as the advances that contributed to the emergence of the concept, are described.
539 citations
TL;DR: There are no viable predictive molecular biomarkers for predicting the severity of ARDS, or molecular-based ARDS therapies, and the proinflammatory cytokines TNF-α (tumor necrosis factor α), interleukin (IL-1β), IL-6, IL-8, and IL-18 are among the most promising as biomarker for predicting morbidity and mortality.
Abstract: Context.—Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a continuum of lung changes arising from a wide variety of lung injuries, frequently resulting in significant morbidity and frequently in death. Research regarding the molecular pathophysiology of ALI/ARDS is ongoing, with the aim toward developing prognostic molecular biomarkers and molecular-based therapy. Objective.—To review the clinical, radiologic, and pathologic features of ALI/ARDS; and the molecular pathophysiology of ALI/ARDS, with consideration of possible predictive/prognostic molecular biomarkers and possible molecular-based therapies. Data Sources.—Examination of the English-language medical literature regarding ALI and ARDS. Conclusions.—ARDS is primarily a clinicoradiologic diagnosis; however, lung biopsy plays an important diagnostic role in certain cases. A significant amount of progress has been made in the elucidation of ARDS pathophysiology and in predicting patient response, however, currently there i...
527 citations
TL;DR: It is indicated that S1P significantly decreases pulmonary/renal vascular leakage and inflammation in a murine model of LPS-mediated acute lung injury and may represent a novel therapeutic strategy for vascular barrier dysfunction.
Abstract: Our prior in vitro studies indicate that sphingosine 1-phosphate (S1P), a phospholipid angiogenic factor, produces endothelial cell barrier enhancement through ligation of endothelial differentiation gene family receptors. We hypothesized that S1P may reduce the vascular leak associated with acute lung injury and found that S1P infusion produced a rapid and significant reduction in lung weight gain (more than 50%) in the isolated perfused murine lung. The effect of S1P was next assessed in a murine model of LPS-mediated microvascular permeability and inflammation with marked increases in parameters of lung injury at both 6 and 24 hours after intratracheal LPS. Each parameter assessed was significantly reduced by intravenous S1P (1 μM final) and in selected experiments by the S1P analogue FTY720 (0.1 mg/kg, intraperitoneally) delivered 1 hour after LPS. S1P produced an approximately 40–50% reduction in LPS-mediated extravasation of Evans blue dye albumin, bronchoalveolar lavage protein content, and lung ti...
487 citations