Rat Lung Research Articles

Comparative analysis of diatom testing and histopathological examination in lungs: An experimental study in Wistar rats

AbstractMicroscopic signs indicative of drowning are not specific to drowning but also to any other form of suffocation where mechanical obstruction is involved. Our study aimed to evaluate both macroscopic and microscopic findings across different groups sharing a common mechanism of death but differing causes and to compare the diatom test with pathohistological examination.Twenty-nine adult Wistar rats, weighing within recommended ranges, were divided into four groups (L1–L4). The diatom test followed established guidelines for diatoms in water from the Bosna River. Microscopic examination revealed diatoms in the lungs of rats in L3 and L4 groups. Pathohistological findings showed varying degrees of changes including consolidation and inflammatory cell infiltration, dominated by lymphocytes and macrophages, with some samples also showing eosinophilic leukocytes.Significant differences were observed between animals whose cause of death was mechanical asphyxia (suffocatio) and those that were submersed for1 hour versus those that were submersed for 72 hours after death. Diatoms identified in group L4 samples 3, 4, and 5 included Navicula sp. (U3 and U6) and Ulnaria ulna (U4).Our findings suggest combining the diatom test with pathohistological analysis to support a drowning diagnosis. Further examination of other organs could enhance result reliability.

Abstract 4118959: Pulmonary Artery-Targeted Metformin-Loaded Nanocapsules Enhance Treatment of Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) remains a therapeutic challenge despite the availability of various medications. Metformin can be able to treat PAH but is associated with significant side effects. This study aims to enhance the efficacy and safety of metformin through a novel drug delivery system using low-dose metformin encapsulated in pulmonary artery-targeted nanocapsules. Methods: Metformin-loaded lung-targeted nanocapsules (MET nanocapsules) were synthesized using a specific lipid composition, including cationic lipids. The uptake and effects on cell viability were assessed in human pulmonary arterial smooth muscle cells (hPASMCs) from both healthy individuals and PAH patients. The therapeutic efficacy of MET nanocapsules was evaluated in a rat model of PAH. Safety was confirmed via serum biochemical tests in rats. Results: MET nanocapsules were successfully synthesized and demonstrated significant inhibition of PASMC proliferation. In the PAH rat model, MET nanocapsule treatment led to improved hemodynamic parameters, reduced right ventricular hypertrophy, and decreased pulmonary arterial medial thickening. Importantly, MET nanocapsules showed effective accumulation in the lungs of PAH rats. Conclusions: Intravenous administration of MET nanocapsules represents a safe and innovative therapeutic approach for PAH. This targeted delivery system has the potential to improve treatment outcomes while minimizing side effects and may have broader applications for other forms of pulmonary hypertension.

Abstract 4122957: C-C motif chemokine receptor-2 disruption Synergizes with Phosphodiesterase Type 5 Inhibition in Ameliorating Pulmonary Hypertension in Monocrotaline-treated Rats: Proof-of-Concept Study for a Combination therapy and Potential Mechanisms

Background: Whether and how any anti-inflammatory agents and their combination with conventional pulmonary vasodilators protect against pulmonary arterial hypertension (PAH) is unknown. Hypothesis: The disruption of C-C motif chemokine receptor (CCR) -2, a receptor for CCL-2, ameliorates PAH in any models with the reversal of the associated pro-inflammatory state and vascular cell phenotypes and synergizes with any conventional pulmonary vasodilators. Methods and Results: By using Ccr2 (-/-) rats generated by CRISPR/ Cas9 , we investigated PAH in Ccr2 (+/+) or Ccr2 (-/-) rats treated with monocrotaline (MCT), SU5416/hypoxia (SuHx), and chronic hypoxia (CH). Ccr2 (-/-) decreased the right ventricular systolic pressure, right ventricular hypertrophy, and mortality rate, and reversed increased expression of inflammatory cytokines/chemokines (IL-6, TNF-α, CCL2, IL-1β, TGF-β) in MCT-treated rats, but not in SuHx or CH models. Consistently, Ccr2 (-/-) decreased indices of pulmonary vascular diseases (PVDs) and perivascular macrophage infiltration, as well as reversed impaired BMPR2 signaling, increased endothelial apoptosis, impaired NO signaling (eNOS, peNOS/eNOS) and decreased phosphodiesterase (PDE)-5 expression in lungs in MCT-treated rats. Gene expression of the receptor for prostaglandin I 2 and endothelin was not altered in MCT-treated rats by Ccr2 (-/-). In cultured pulmonary arterial smooth muscle cells (PASMCs), Ccr2 (-/-) suppressed CCL2-induced hyperproliferation and dedifferentiation as well as reversed CCL2-induced decrease in PDE5 expression. Consistently, the whole-genome RNA sequencing analysis identified differentially expressed genes in CCL2-stimulated Ccr2 (-/-) PASMCs, which are related to cellular differentiation and contraction. Based on studies in rats and cultured PASMCs, we investigated whether a PDE5 inhibitor, tadalafil, synergizes with Ccr2 (-/-). Tadalafil administration ameliorated PH and PVDs in MCT-treated Ccr2 (-/-) rats but not in Ccr2 (+/+) rats, and further improved survival in Ccr2 (-/-) rats. Conclusions: PDE5 inhibition synergized with Ccr2 disruption in protecting against PAH in MCT-treated rats, which was mechanistically related to the restoration of proinflammatory states and associated vascular cell phenotypes. These findings confer a fundamental basis supporting that CCR2 may be a therapeutic target in intractable PAH patients with a certain CCR2-related inflammatory phenotype and refractory to conventional pulmonary vasodilators.

Effect of tadalafil on pulmonary hypoplasia in congenital diaphragmatic hernia of rat fetuses

Background. Pulmonary hypoplasia and persistent pulmonary hypertension in congenital diaphragmatic hernia are the cause of adverse perinatal outcomes. Dissatisfaction with the outcomes of intrauterine surgical correction of CDH determines the search for alternative non-surgical prenatal methods of treating pulmonary hypoplasia in CDH. Objective. To study the effect of a reversible selective inhibitor of specific phosphodiesterase type 5 (tadalafil) on the development of fetal lungs in rats in a model of congenital diaphragmatic hernia. Design and methods. An experimental study was conducted on the possibility of correcting fetal lung hypoplasia in rats when modeling a diaphragmatic hernia with nitrophen (100 mg orally, once on the 9th day of pregnancy). Results. Congenital diaphragmatic hernia was recorded in 12.5 % of offspring. Subcutaneous administration of tadalafil to pregnant rats (0,83 mg/kg, for 10 days, from the 9th day of pregnancy) in the lungs of fetuses increases the number of alveoli (by 22 % at p ≤ 0.05), the area of microvasculature vessels and the volume of lung parenchyma increases (by 1.25 % and 1.13 % more (at p ≤ 0.05)). Conclusion. The results obtained from the first experiment conducted in the Russian Federation to study the effect of tadalafil on the lungs in congenital diaphragmatic hernia of the fetus are comparable with the data of the authors who used sildenafil, however, the use of tadalafil seems more optimal due to the ease of its administration for potential practical use.

Circulating mtNFPs Are Associated with ARDS after CPB and Regulate Endothelial Barrier through FPR2.

Cardiopulmonary bypass (CPB) increases the risk of acute respiratory distress syndrome (ARDS) due to endothelial cell (EC) barrier dysfunction. However, the specific role of mitochondrial N-formyl peptides (mtNFPs) in ARDS following CPB remains unexplored. Here, we investigated the differential expression of circulating mtNFPs in patients after CPB, focusing on the novel role of FPR2 in ECs. Levels of circulating mtNFPs were assessed using enzyme-linked immunosorbent assay (ELISA). Several mtNFPs (ND4, ND5, ND6, and Cox1) were significantly upregulated in patients with ARDS at day 1 post-CPB compared to patients without ARDS. Higher levels of ND6 were correlated with worst PaO2/FiO2 (r=-0.2219 and P<0.0001) and cardiac Troponin T (r=2.107 and P<0.0001). Utilizing patient-derived serum and a rat lung ischemia reperfusion injury (LIRI) model, we observed a positive correlation between serum ND6 concentration and ARDS, which is also associated with EC barrier dysfunction. In vitro experiments, using trans-endothelial electric resistance (TEER) measurements and fluorescence microscopy with FITC-labeled VE-cadherin, demonstrated that ND6 disrupts the EC barrier through FPR2. Furthermore, FPR2 controls the release of ND6 out of mitochondria and cytoplasm under hypoxia reoxygenation (HR). Activated FPR2 leads to upregulation of nuclear transcription factor-kappa B (NF-κB) by inducing IκBα phosphorylation, promoting ICAM1 and VCAM1 expression, thereby compromising EC barrier integrity. Circulating pro-inflammatory and barrier-disruptive mtNFPs, particularly ND6, are associated with ARDS in patients undergoing CPB. The novel ND6-FPR2 axis regulates inflammation and EC permeability through the NF-κB pathway.

Regional variations in hyperpolarized 129Xe lung MRI: Insights from CSI-CSSR and CSSR in healthy and irradiated rat models.

To compare pulmonary function metrics obtained with hyperpolarized xenon-129 (HXe) MRS, using chemical shift saturation recovery (CSSR) and CSI-CSSR, in healthy rats and a rat model of radiation-induced lung injury. HXe-MR data were acquired in two healthy rats and one rat with radiation-induced lung injury using whole-lung spectroscopy and CSI-CSSR techniques. The CSI-CSSR acquisitions were performed with both fixed TE and variable TE. Apparent alveolar septal wall thickness, gas transfer dynamics, and regional lung function were quantified and compared across acquisition methods. Spectral analysis included alignment of dissolved-phase frequency spectra using the membrane resonance as reference, segmentation of gas-phase (GP) frequency distribution, and characterization of gas uptake in the vasculature. Complex GP line shapes were observed in rat lungs, necessitating pixel-wise CSI analysis and membrane resonance alignment for improved quantification. Notable differences in alveolar septal wall thickness, dissolved-phase GP ratios, and GP and red blood cell frequencies were found between acquisition techniques and lung conditions. CSI-CSSR provided unique insights into regional lung function, including the identification of distinct GP frequency zones potentially corresponding to different airway structures, and the ability to map relative xenon gas transport. Metrics from fixed-TE and variable-TE acquisitions usually differed by less than 10%, but the latter yielded a 20% SNR gain. HXe-MRS and CSI-CSSR techniques provide similar but not universally interchangeable insights into lung function, particularly in the presence of pathology.

Traditional Chinese Herbal Medicine: Therapeutic Potential in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow obstruction and manifested by symptoms such as chronic cough, sputum, and dyspnea. Traditional Chinese medicine (TCM) has long been used to treat COPD. This article summarizes potential Chinese herbal medicines (CHM) for COPD treatment through a literature review and collation. The findings highlight 14 kinds of effective CHM for COPD, including Scutellaria radix, Salvia miltiorrhiza radix et rhizoma, Hippophae fructus, Ginseng radix et rhizoma, and Astragali radix. Flavonoids, terpenoids, alkaloids, and volatile oil constituents are the main bioactive components for the treatment of COPD. They mainly inhibit the tumor necrosis factor alpha/nuclear factor kappa B (TNF-α/NF-κB) signaling pathway by reducing the production and release of inflammatory factors such as interleukin 1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), TNF-α, and NF-κB, thereby reducing inflammation in lungs of rats with COPD and protect the lung tissues. Some active ingredients can inhibit toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase-protein kinase B (PI3K-Akt), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and transforming growth factor beta (TGF-β) signaling pathways to express anti-inflammatory activity. This work establishes a foundation for using CHM in COPD treatment and offers new insights and approaches for developing novel anti-COPD drugs.

The Effects of Turmeric and Mangosteen Pericarp Ethanol Extract on Eosinophil Count, TNF-α and TGF-β1 Gene Expression in Asthmatic Rat Model.

Asthma is a chronic respiratory disease that is characterized by inflammation, bronchial hyperreactivity, and airway remodeling. The long-term use of corticosteroids at high doses causes various side effects. Traditional herbal medicine has been suggested as an alternative therapy that is safe and effective in dealing with asthma. Natural plants such as turmeric and mangosteen are known to treat asthma and reduce inflammation. The purpose of this study was to investigate the effects of turmeric and mangosteen pericarp ethanol extracts on the eosinophil counts, TNF-α and TGF-β1 gene expression, and inflammatory cell counts in the histopathology of an asthmatic rat model. The preliminary study used 30 rats, which were divided into a normal group, negative control group (OVA-sensitized), turmeric normal group, mangosteen group, and positive control group. Blood samples were collected after the sensitization period to determine eosinophil counts. TNF-α and TGF-β1 gene expression, and histopathology were observed in the rat's lungs. The follow-up study used 30 rats divided into a normal group, negative control group (OVA-sensitized), combination of turmeric and mangosteen group (54m/200gr rats, 36mg/200gr rats, and 36mg/200gr rats), and positive control group. The examination procedures were the same as in the preliminary study. The administration of single ethanol extracts of turmeric and mangosteen significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p<0.05). The combination of turmeric and mangosteen extracts at all doses significantly decreased eosinophils and improved the histopathological features of the lungs (inflammatory cell counts, bronchial inflammatory score, and bronchial smooth muscle thickness) (p<0.05). Both the single and combined administration of turmeric and mangosteen ethanol extracts did not cause significant changes in TNF-alpha and TGF-beta (p>0.05). Turmeric ethanol extract and mangosteen pericarp ethanol extract have a reductional effect on the parameters of asthma based on the eosinophil counts, the inflammatory cell counts and score, and bronchial smooth muscle thickness.

Magnolol preserves the integrity of the intestinal epithelial barrier and mitigates intestinal injury through activation of PPAR γ in COPD rat

Ethnopharmacological relevanceMagnolia officinalis Rehder & E.H. Wilson is traditionally used in the treatment of gastrointestinal disorders, diarrhea, and cough. Its main active ingredient, magnolol, exhibits protective effects on the lungs and gastrointestinal tract, including the inhibition of inflammation in these organs. Aim of the studyThis work aims to explore the molecular mechanism by which magnolol suppressed Chronic obstructive pulmonary disease (COPD) intestinal damage by improving the intestinal epithelial barrier. Materials and methodsThe study focused on investigating the mitigation effect of magnolol on intestinal injury and epithelial barrier in a COPD rat. Caco-2 cells were induced with TNF-α or IL-1β to establish the barrier injury model in order to explore the direct protective effect of magnolol on the intestinal barrier and elucidate the molecular mechanism by which it activates peroxisome proliferators-activated receptors-γ (PPARγ). ResultsMagnolol significantly improves pulmonary function and tissue damage in COPD rats by inhibiting inflammation, protease imbalance, and oxidative stress. It also suppresses colon tissue damage and inflammation, and protects colon epithelial barrier function by suppressing the decline of tight junction proteins, reducing colon epithelial permeability. In Caco-2 cells, magnolol directly reduces monolayer permeability, increases TEER, and upregulates tight junction protein expression induced by TNF-α or IL-1β. Drug Affinity Responsive Target Stability (DARTS) and thermal shift assays show that magnolol effectively binds to SRC, activating PPARγ signaling in Caco-2 cells and colon tissues of COPD rats. Furthermore, magnolol enhances the binding of PPARγ and RXRα, promoting their activation and entry into the nucleus. The PPARγ inhibitor GW9662 can reverse the effects of magnolol on PPARγ activation and tight junction protein upregulation in IL-1β or TNF-α induced Caco-2 cells. ConclusionsThis work demonstrates that magnolol enhances lung and intestinal functions in COPD rats, and elucidates its mechanism of action in protecting the intestinal epithelial barrier by activating PPARγ.

Immunohistochemical and molecular study for differential diagnosis between freshwater and saltwater drowning

The postmortem identification of drowning in the field of forensic medicine is difficult due to unspecific autopsy findings, and usually, it is a “diagnosis of exclusion”. A model of drowning in salt and fresh water was established to discuss the postmortem changes after drowning and the differences between saltwater drowning (SWD) and freshwater drowning (FWD). The organs (brain and ‘lung) of 30 rats were extracted at three-time points (0 h, 24 h, and 48 h) after drowning. The histopathological, immunohistochemical,l, and molecular changes in the lung and brain of rats at different time points were investigated. Results show no significant difference in pathological findings between fresh and saltwater drowning. Casp3, JNK, and ERK all showed a rise in their postmortem expression in a time-dependent way; the expression of these three genes is much greater in cases of saltwater drowning compared to cases of freshwater drowning. So, it is concluded that after 24 h and 48 h from death, potent cellular oxidative stress occurred and caused the upregulation of the studied genes.

Exploring an indirect quantification strategy for PFOA in rat tissues via efficient degradation and fluorescence spectroscopy

Perfluorooctanoic acid (PFOA) has aroused global attention due to its persistence, biotoxicity and bioaccumulative properties. Monitoring PFOA levels in biological samples could give significant insights into its toxicity mechanism and health risk evaluation. Herein, to explore the distribution of PFOA in biological tissues, an indirect quantitation strategy for PFOA in biological samples was proposed based on fluorescence spectroscopy. F- ion was produced through highly efficient degradation of PFOA in polar aprotic solvent, and then F- ion was detected with highly selective F- ion fluorescent probe, which enabled the indirect quantitative detection of PFOA in biological samples. The sensitivity for PFOA was exhibited with limit of detection of 3.55 μM. The method’s accuracy and precision were validated by spiked biological sample experiment, with recovery rate ranging from 93.2 % to 105.5 % and relative standard deviation below 9.2 %. The content of PFOA was successfully detected in rats livers, kidneys and lungs tissues. Density function theory was employed to explore defluorination pathway, indicating that heating, alkaline and water conditions played a crucial role in the degradation of PFOA to produce F- ion. Thus, this novel strategy is suitable for quantitative analysis of PFOA in biological samples with high selectivity, sensitivity, recovery ratio, and simple sample preparation, which also provides a strategy for evaluating the levels of per- and polyfluoroalkyl substances in biological samples.

Yohimbine treatment improves pulmonary fibrosis by attenuating the inflammation and oxidative stress via modulating the MAPK pathway

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disorder characterized by the accumulation of extracellular matrix and collagen, resulting in significant parenchymal scarring and respiratory failure that leads to mortality. Yohimbine (YBH) is an α-2 adrenergic receptor antagonist with anti-oxidant and anti-inflammatory properties. In the current study, we aimed to investigate the anti-inflammatory, anti-oxidant and anti-fibrotic activity of YBH against LPS/TGF-β-induced differentiation in BEAS-2B/LL29 cells and bleomycin (BLMN) induced pulmonary fibrosis model in rats. Network pharmacology, gene expression, Western-blot analysis, immune-cytochemistry/immunohistochemistry, lung function and histology techniques were used to assess the fibrotic marker expression/levels in cells or rat lung tissues. YBH treatment significantly attenuated the LPS-induced pro-inflammatory (identified through a network-pharmacology approach) and oxidative stress markers expression in lung epithelial cells. TGF-β stimulation significantly elevated the fibrotic cascade of markers and treatment with YBH attenuated these markers’ expression/levels. Intra-tracheal administration of BLMN caused a significant elevation of various inflammatory/oxidative stress and fibrotic markers expression in lung tissues and treatment with YBH significantly mitigated the same. Ashcroft score analysis revealed that BLMN exhibited severe distortion of the lungs, elevation of thickness of the alveolar walls and accumulation of collagen in tissues, further treatment with YBH significantly suppressed these events and improved the lung architecture. Lung functional parameters demonstrated that BLMN-induced stiffness and resistance were reduced considerably upon YBH treatment and restored lung function dose-dependently. Overall, this study reveals that YBH treatment significantly attenuated the BLMN-induced fibrosis by regulating the MAPK pathway and provided insightful information for progressing towards translational outcomes.

Long-term pulmonary repair in rat lungs after sublobar resection: electrocautery versus stapler methods.

We investigated and compared the long-term (6-month) histologic changes in a rat model of sublobar resection created using electrocautery or stapler techniques. Nine-week-old male rats were anesthetized and intubated; thoracotomy with sublobar resection was performed in the right middle lobe using electrocautery or stapler techniques. Histological examination was performed at 2, 4, 8, 12, and 24weeks post-surgery to assess long-term effects on lung tissue repair and morphologic changes. Lung expansion and alveolar epithelial cell proliferation were evaluated by measuring the mean linear intercept and counting the number of alveolar type I and II cells. The electrocautery group showed signs of lung self-repair at the resected area over time, with inflammatory cell infiltration followed by growth of vessels and bronchioles. Mesothelial cells covered the resected area by 2weeks; elastic fibers gradually connected from both sides by 24weeks. Lung expansion, measured by mean linear intercept, was initially small below the electrocautery resection area at 2weeks but recovered from 4 to 24weeks. The stapler group showed persistently small mean linear intercept over time. In the electrocautery group, the number of alveolar type II cells was higher just below the resection than in other areas from 2 to 24weeks, followed by alveolar type I cells (4 to 24weeks). The stapler group showed a transient alveolar type II cell increase at 2weeks. Compared to the stapler technique, electrocautery mayprovide advantages for postoperative lung repair by promoting lung expansion and alveolar epithelial cell proliferation.

Apigenin's Influence on Inflammatory and Epigenetic Responses in Rat Lungs After Radiotherapy.

The lung is a moderately radio-sensitive organ. When cells are damaged due to accidental radiation exposure or treatment, they release molecules that lead to the recruitment of immune cells, accumulating inflammatory cytokines at the site of damage. Apigenin (Api) is a natural flavonoid known for its anti-inflammatory properties. In this study, we investigated the radioprotective properties of Api in the lung. Thirty-six Wistar rats were randomly assigned to nine groups: control, radiation (Rad), CMC+Rad, Api10+Rad, and Api20+Rad. Api was administered with an intraperitoneal injection for 7 days, after which the rats were irradiated with 6 Gy whole-body X-ray. At 6 and 72 hours post-irradiation, the rats were euthanized, and their lung tissue was extracted. Radiation led to increased alveolar wall thickness and the infiltration of macrophages and lymphocytes. Furthermore, the expression levels of inflammatory factors such as a nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-ĸB), Glycogen synthase kinase-3 beta (GSK-3β), transforming growth factor-beta1 (TGF-β1), and epigenetic factors including DNA methyltransferase 3a (DNMT3a) and Histone deacetylase 2 (HDAC2) were elevated in the lung tissue following radiation. Meanwhile, the expression level of IκB-α decreased. However, administration of Api (at both 10&20 mg/kg) reversed the adverse effects of radiation. Api administration mitigated radiation-induced lung damage by reversing inflammatory and epigenetic changes.

Establishment of a Novel Ex Vivo Lung Perfusion System for Rat Lungs After Circulatory Death

Establishment of a Novel Ex Vivo Lung Perfusion System for Rat Lungs After Circulatory Death

Ficus carica Puree Exerts a Higher Antioxidative Profile in Hypoxic Lungs after Intermittently Inducing Hypoxia in Sprague–Dawley Rats

Abstract Background: The body produces more hypoxia-inducible factor and reactive oxygen species in response to hypoxic situations because they cause unbalanced oxygen levels. Ficus carica provides numerous benefits because of its high antioxidant and mineral content. Nevertheless, the mechanism by which F. carica consumption confers this protective benefit remains incompletely understood. Aim: This study aimed to evaluate how F. carica puree (FCP) can affect the antioxidant enzyme activity and malondialdehyde (MDA) levels in the lung by mitigating the effects of intermittent hypoxia (IH). Methods: Thirty Sprague–Dawley rats were divided into five groups negative control (NC), untreated; positive control (PC), treated with aquadest; FCP1; FCP2; and FCP3, which received FCP at doses of 1.25, 2.5, and 5 mL/200 g body weight. The treatment was administered for 4 weeks before inducing IH (10% O2 and 90% N2) into all groups (except NC) for 4 h for 7 days. Furthermore, hemoglobin (Hb) level, lung MDA level, and lung superoxide dismutase (SOD) enzyme activity were assessed. Results: The Hb level did not exhibit a significant increase under IH conditions. Conversely, the PC group exhibited the least activity of lung antioxidant enzymes and the highest lung MDA levels. In addition, the FCP intervention group exhibited lower MDA levels than the PC group and ameliorated relative lung weight loss. Conclusion: All FCP intervention groups showed lower MDA levels and higher SOD levels compared to the PC group, suggesting that FCP could mitigate the effects of hypoxia in rat lungs.

Hexavalent chromium exposure induces lung injury via activation of NLRP3 and AIM2 inflammasomes in rats

Hexavalent chromium (Cr(VI)) has been identified as a Class I human carcinogen, but its carcinogenic mechanism is currently unclear. There is still a lack of understanding of its associations with early pulmonary inflammatory damages. Inflammation is an important stage before the occurrence of tumors, and under the long-term stimulation of inflammation, it can promote the development of tumors. In this study, the aim is to explore the effect of Cr(VI) exposure on pulmonary inflammation and its relationship with the mechanism of inflammation cancer transformation. We established a Cr(VI) exposure model in SD rats using tracheal instillation of potassium dichromate solution, and collected samples at the time of cessation of exposure and 14 days after cessation of exposure. Analyzing the experimental results, it was found that the lung index increased after exposure to Cr(VI), promoting the occurrence of apoptosis in lung tissue cells and exacerbating lung tissue damage. The damage situation improved after exposure termination; Inductively coupled plasma mass (ICPRQ) spectrometer detection found that the exposed group had significantly increased levels of blood chromium, blood manganese, blood copper, blood arsenic, urine chromium, urine copper, and urine lead; After two weeks of repair, blood chromium and blood manganese levels were significantly lower than those in the same dose group of the exposure group, while blood copper levels were significantly higher than those in the same dose group of the exposure group. There was no significant difference in blood arsenic levels between the exposure group and the exposure group. Urine chromium and urine lead levels were significantly lower than those in the same dose group of the exposure group, while urine copper levels only increased. At the same time, it was found that Cr(VI) exposure caused disruption of oxidative stress levels in rat lung tissues. After 14-day exposure, Cr(VI) significantly decreased and oxidative stress levels significantly decreased. Further investigation revealed that Cr(VI) induces activation of inflammasomes NLRP3, AIM2, and their signaling pathways in lung inflammatory injuries, but this condition persists even after cessation of exposure. The study suggested that in hexavalent chromium induced lung tissue injuries in rats, NLRP3 and AIM2 inflammasomes and their signaling pathways activation. Furthermore, the characteristic of sustained activation after cessation of exposure was also indicated. These results provide new ideas and references for further elucidating the mechanisms of Cr(VI), lung inflammation and inflammation cancer transformation.

The Role of Mast Cells in the Remodeling Effects of Molecular Hydrogen on the Lung Local Tissue Microenvironment under Simulated Pulmonary Hypertension

Molecular hydrogen (H2) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H2 on lung inflammation and blood pressure. In this study, we further focused the biological effects of H2 on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment. MPH resulted in a significantly increased number of MCs in both the pneumatic and respiratory parts of the lungs, an increased number of tryptase-positive MCs with increased expression of TGF-β, activated interaction with immunocompetent cells (macrophages and plasma cells) and fibroblasts, and increased MC colocalization with a fibrous component of the extracellular matrix of connective tissue. The alteration in the properties of the MC population occurred together with intensified collagen fibrillogenesis and an increase in the integral volume of collagen and elastic fibers of the extracellular matrix of the pulmonary connective tissue. The exposure of H2 together with monocrotaline (MCT), despite individual differences between animals, tended to decrease the intrapulmonary MC population and the severity of the fibrotic phenotype of the local tissue microenvironment compared to changes in animals exposed to the MCT effect alone. In addition, the activity of collagen fibrillogenesis associated with MCs and the expression of TGF-β and tryptase in MCs decreased, accompanied by a reduction in the absolute and relative content of reticular and elastic fibers in the lung stroma. Thus, with MCT exposure, inhaled H2 has antifibrotic effects involving MCs in the lungs of rats. This reveals the unknown development mechanisms of the biological effects of H2 on the remodeling features of the extracellular matrix under inflammatory background conditions of the tissue microenvironment.

MiR-24 regulates obstructive pulmonary disease in rats via S100A8

Purpose Chronic obstructive pulmonary disease (COPD) is a persistent inflammatory disorder characterized by minor airway inflammation and emphysema involving various cell types and cytokines. MicroRNAs (miRNAs) have emerged as critical regulators in the pathogenesis of lung diseases. This study investigates the impact of microRNA-24 (miR-24) on airway inflammatory responses in a rat model of COPD. Materials and methods The model was established by combining cigarette smoke exposure and lipopolysaccharide stimulation, and rat lung tissues were transfected with adeno-associated viruses overexpressing miR-24. Pathological changes in the lung were assessed using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, and interleukin-8, were measured using enzyme-linked immunosorbent assay. Expression of miR-24 and S100A8 was detected through quantitative reverse transcription PCR, while protein levels of S100A8, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) were assessed using western blotting. Bioinformatics analysis and dual-luciferase reporter assay were performed to determine the relationship between S100A8 and miR-24. Results The results demonstrated the downregulation of miR-24 in rats with COPD, and its overexpression resulted in a significant decrease in S1008 mRNA levels. Additionally, the protein level of S100A8 was significantly increased in the lung tissues of COPD rats. The upregulation of miR-24, however, not only inhibited the protein expression of S100A8, TLR4, and MyD88 in lung tissues but also reduced the release of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid, thereby attenuating inflammatory responses and pathological injuries in the lung. Conclusions Our data suggest that miR-24 attenuates airway inflammatory responses in COPD by inhibiting the TLR4/MyD88 pathway via targeting S100A8.

Angiotensin-converting enzyme 2 activation attenuates inflammation and oxidative stress in brain death donor followed by rat lung transplantation

Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1β (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.