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1.
J Ethnopharmacol ; 333: 118404, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38824977

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis presents complex pathophysiological challenges. Taohe Chengqi Decoction (THCQ), a traditional Chinese medicine, offers potential in managing sepsis-related complications, though its exact mechanisms are not fully understood. AIM OF THE STUDY: This research aimed to assess the therapeutic efficacy and underlying mechanisms of THCQ on sepsis-induced lung injury. MATERIALS AND METHODS: The study began with validating THCQ's anti-inflammatory effects through in vitro and in vivo experiments. Network pharmacology was employed for mechanistic exploration, incorporating GO, KEGG, and PPI analyses of targets. Hub gene-immune cell correlations were assessed using CIBERSORT, with further scrutiny at clinical and single-cell levels. Molecular docking explored THCQ's drug-gene interactions, culminating in qPCR and WB validations of hub gene expressions in sepsis and post-THCQ treatment scenarios. RESULTS: THCQ demonstrated efficacy in modulating inflammatory responses in sepsis, identified through network pharmacology. Key genes like MAPK14, MAPK3, MMP9, STAT3, LYN, AKT1, PTPN11, and HSP90AA1 emerged as central targets. Molecular docking revealed interactions between these genes and THCQ components. qPCR results showed significant modulation of these genes, indicating THCQ's potential in reducing inflammation and regulating immune responses in sepsis. CONCLUSION: This study sheds light on THCQ's anti-inflammatory and immune regulatory mechanisms in sepsis, providing a foundation for further research and potential clinical application.


Assuntos
Anti-Inflamatórios , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Sepse , Sepse/tratamento farmacológico , Sepse/complicações , Sepse/imunologia , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Humanos , Lesão Pulmonar/tratamento farmacológico , Farmacologia em Rede , Modelos Animais de Doenças
2.
Int Immunopharmacol ; 137: 112450, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38906007

RESUMO

Inflammation, apoptosis and oxidative stress play crucial roles in the deterioration of severe acute pancreatitis-associated acute respiratory distress syndrome (SAP-ARDS). Unfortunately, despite a high mortality rate of 45 %[1], there are limited treatment options available for ARDS outside of last resort options such as mechanical ventilation and extracorporeal support strategies[2]. This study investigated the potential therapeutic role and mechanisms of AQP9 inhibitor RG100204 in two animal models of severe acute pancreatitis, inducing acute respiratory distress syndrome: 1) a sodium-taurocholate induced rat model, and 2) and Cerulein and lipopolysaccharide induced mouse model. RG100204 treatment led to a profound reduction in inflammatory cytokine expression in pancreatic, and lung tissue, in both models. In addition, infiltration of CD68 + and CD11b + cells into these tissues were reduced in RG100204 treated SAP animals, and edema and SAP associated tissue damage were improved. Moreover, we demonstrate that RG100204 reduced apoptosis in the lungs of rat SAP animals, and reduces NF-κB signaling, NLRP3, expression, while profoundly increasing the Nrf2-dependent anti oxidative stress response. We conclude that AQP9 inhibition is a promising strategy for the treatment of pancreatitis and its systemic complications, such as ARDS.


Assuntos
Fator 2 Relacionado a NF-E2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Pancreatite , Síndrome do Desconforto Respiratório , Transdução de Sinais , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Pancreatite/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Camundongos , Ratos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Aquaporinas/metabolismo , Aquaporinas/antagonistas & inibidores , Modelos Animais de Doenças , Ratos Sprague-Dawley , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Ácido Taurocólico , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Pâncreas/patologia , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ceruletídeo , Humanos , Heme Oxigenase (Desciclizante)/metabolismo
3.
Sci Rep ; 14(1): 14231, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902260

RESUMO

Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a "two-hit" rat model and "two-hit" cell model to prove our hypothesis. Rats were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 µM and 8 µM) (OA + LPS + 4 µM and OA + LPS + 8 µM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the "two-hit" induced lung injury, the expression of TNF, IL-1ß, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the "two-hit" cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate "two-hit"-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.


Assuntos
Lesão Pulmonar Aguda , Apoptose , Butorfanol , Inflamação , Animais , Butorfanol/farmacologia , Apoptose/efeitos dos fármacos , Ratos , Masculino , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Fator de Transcrição RelA/metabolismo , Lipopolissacarídeos , Ratos Sprague-Dawley , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/prevenção & controle , Modelos Animais de Doenças , Citocinas/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo
4.
Drug Res (Stuttg) ; 74(5): 241-249, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38830372

RESUMO

Pentoxifylline (PTX), a non-selective phosphodiesterase inhibitor, has demonstrated protective effects against lung injury in animal models. Given the significance of pulmonary toxicity resulting from paraquat (PQ) exposure, the present investigation was designed to explore the impact of PTX on PQ-induced pulmonary oxidative impairment in male mice.Following preliminary studies, thirty-six mice were divided into six groups. Group 1 received normal saline, group 2 received a single dose of PQ (20 mg/kg; i.p.), and group 3 received PTX (100 mg/kg/day; i.p.). Additionally, treatment groups 4-6 were received various doses of PTX (25, 50, and 100 mg/kg/day; respectively) one hour after a single dose of PQ. After 72 hours, the animals were sacrificed, and lung tissue was collected.PQ administration caused a significant decrease in hematocrit and an increase in blood potassium levels. Moreover, a notable increase was found in the lipid peroxidation (LPO), nitric oxide (NO), and myeloperoxidase (MPO) levels, along with a notable decrease in total thiol (TTM) and total antioxidant capacity (TAC) contents, catalase (CAT) and superoxide dismutase (SOD) enzymes activity in lung tissue. PTX demonstrated the ability to improve hematocrit levels; enhance SOD activity and TTM content; and decrease MPO activity, LPO and NO levels in PQ-induced pulmonary toxicity. Furthermore, these findings were well-correlated with the observed lung histopathological changes.In conclusion, our results suggest that the high dose of PTX may ameliorate lung injury by improving the oxidant/antioxidant balance in animals exposed to PQ.


Assuntos
Antioxidantes , Peroxidação de Lipídeos , Pulmão , Paraquat , Pentoxifilina , Superóxido Dismutase , Animais , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Paraquat/toxicidade , Camundongos , Masculino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Antioxidantes/farmacologia , Superóxido Dismutase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Catalase/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Inibidores de Fosfodiesterase/uso terapêutico , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Diester Fosfórico Hidrolases/metabolismo
6.
Am J Physiol Lung Cell Mol Physiol ; 327(2): L141-L149, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38772909

RESUMO

Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though the presence of neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain. The goal of this study was to elucidate the role of neutrophils in a clinically relevant model of bacterial pneumonia. We investigated the effect of reducing neutrophils in a mouse model of pneumococcal pneumonia treated with antibiotics. Neutrophils were reduced with anti-lymphocyte antigen 6 complex locus G6D (Ly6G) monoclonal antibody 24 h before and immediately preceding infection. Mice were inoculated intranasally with Streptococcus pneumoniae and received ceftriaxone 12 h after bacterial inoculation. Neutrophil reduction in mice treated with ceftriaxone attenuated hypoxemia, alveolar permeability, epithelial injury, pulmonary edema, and inflammatory biomarker release induced by bacterial pneumonia, even though bacterial loads in the distal air spaces of the lung were modestly increased as compared with antibiotic treatment alone. Thus, when appropriate antibiotics are administered, lung injury in the early phase of bacterial pneumonia is mediated in part by neutrophils. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.NEW & NOTEWORTHY Neutrophil accumulation is a key feature of ARDS, but their contribution to the pathogenesis is still uncertain. We investigated the effect of reducing neutrophils in a clinically relevant mouse model of pneumococcal pneumonia treated with antibiotics. When appropriate antibiotics were administered, neutrophil reduction with Ly6G antibody markedly attenuated lung injury and improved oxygenation. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.


Assuntos
Camundongos Endogâmicos C57BL , Neutrófilos , Pneumonia Pneumocócica , Animais , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/patologia , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Camundongos , Streptococcus pneumoniae/patogenicidade , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/microbiologia , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Lesão Pulmonar/patologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/tratamento farmacológico , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/imunologia , Masculino
7.
Surgery ; 176(2): 499-510, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38811326

RESUMO

BACKGROUND: Emodin, a natural anthraquinone derivative found in various Chinese medicinal herbs, has been proved to be an effective therapeutic agent in the treatment of many diseases. However, its effect on lung injury after intestinal ischemia/reperfusion injury remains unknown. This research was designed to investigate whether emodin protects against intestinal ischemia/reperfusion-induced lung injury and to elucidate the underlying molecular mechanisms in vivo and in vitro. METHODS: Intestinal ischemia/reperfusion injury was induced by occluding the superior mesenteric artery in mice, and mouse lung epithelial-12 cells were subjected to oxygen-glucose deprivation and reoxygenation to establish an in vitro model. RESULTS: Our data indicated that emodin treatment reduced intestinal ischemia/reperfusion-induced oxidative stress, inflammation and apoptosis in lung tissues and alleviated lung injury. However, the protective effects of emodin on intestinal ischemia/reperfusion-induced lung injury were reversed by the protein kinase B inhibitor triciribine or the heme oxygenase-1 inhibitor tin protoporphyrin IX. The protein kinase inhibitor triciribine also downregulated the expression of heme oxygenase-1. CONCLUSION: In conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion.


Assuntos
Emodina , Heme Oxigenase-1 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Traumatismo por Reperfusão , Transdução de Sinais , Regulação para Cima , Animais , Emodina/farmacologia , Emodina/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/tratamento farmacológico , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Heme Oxigenase-1/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Intestinos/irrigação sanguínea , Intestinos/patologia , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Lesão Pulmonar/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/patologia , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Membrana
8.
Biomed Environ Sci ; 37(4): 367-376, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38727159

RESUMO

Objective: This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods: Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results: Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1ß, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. Conclusion: SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5-induced lung injury.


Assuntos
Glucosídeos , Lesão Pulmonar , Camundongos Endogâmicos C57BL , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fenóis , Sirtuína 1 , Animais , Camundongos , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Lesão Pulmonar/tratamento farmacológico , Tamanho da Partícula , Material Particulado/toxicidade , Material Particulado/efeitos adversos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuína 1/efeitos dos fármacos , Sirtuína 1/genética , Sirtuína 1/metabolismo
9.
Pflugers Arch ; 476(7): 1125-1143, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38700719

RESUMO

Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA's potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Hipertireoidismo , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Ratos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Masculino , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/complicações , Hipertireoidismo/metabolismo , Ratos Wistar , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Lesão Pulmonar/etiologia , Citocinas , Nicotinamida Fosforribosiltransferase
10.
Sci Prog ; 107(2): 368504241257060, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38807538

RESUMO

INTRODUCTION: Ischemia-reperfusion (IR) injury is a major concern that frequently occurs during vascular surgeries. Hydrogen-rich saline (HRS) solution exhibits antioxidant and anti-inflammatory properties. This study aimed to examine the effects of HRS applied before ischemia in the lungs of rats using a lower extremity IR model. MATERIAL AND METHODS: After approval was obtained from the ethics committee, 18 male Wistar albino rats weighing 250-280 g were randomly divided into three groups: control (C), IR and IR-HRS. In the IR and IR-HRS groups, an atraumatic microvascular clamp was used to clamp the infrarenal abdominal aorta, and skeletal muscle ischemia was induced. After 120 min, the clamp was removed, and reperfusion was achieved for 120 min. In the IR-HRS group, HRS was administered intraperitoneally 30 min before the procedure. Lung tissue samples were examined under a light microscope and stained with hematoxylin-eosin (H&E). Malondialdehyde (MDA) levels, total sulfhydryl (SH) levels, and histopathological parameters were evaluated in the tissue samples. RESULTS: MDA and total SH levels were significantly higher in the IR group than in the control group (p < 0.0001 and p = 0.001, respectively). MDA and total SH levels were significantly lower in the IR-HRS group than in the IR group (p < 0.0001 and p = 0.013, respectively). A histopathological examination revealed that neutrophil infiltration/aggregation, alveolar wall thickness, and total lung injury score were significantly higher in the IR group than in the control group (p < 0.0001, p = 0.001, and p < 0.0001, respectively). Similarly, alveolar wall thickness and total lung injury scores were significantly higher in the IR-HRS group than in the control group (p = 0.009 and p = 0.004, respectively). A statistically significant decrease was observed in neutrophil infiltration/aggregation and total lung injury scores in the IR-HRS group compared to those in the IR group (p = 0.023 and p = 0.022, respectively). CONCLUSION: HRS at a dose of 20 mg/kg, administered intraperitoneally 30 min before ischemia in rats, reduced lipid peroxidation and oxidative stress, while also reducing IR damage in lung histopathology. We believe that HRS administered to rats prior to IR exerts a lung-protective effect.


Assuntos
Hidrogênio , Pulmão , Malondialdeído , Músculo Esquelético , Ratos Wistar , Traumatismo por Reperfusão , Solução Salina , Animais , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/tratamento farmacológico , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Ratos , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/irrigação sanguínea , Solução Salina/farmacologia , Solução Salina/química , Solução Salina/administração & dosagem , Hidrogênio/farmacologia , Hidrogênio/administração & dosagem , Malondialdeído/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/tratamento farmacológico
11.
Poult Sci ; 103(7): 103860, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795514

RESUMO

A large amount of hydrogen sulfide (H2S) is produced in the process of chicken breeding, which can cause serious inflammation and oxidative damage to the respiratory system of chickens. Tea tree oil (TTO) has antioxidant and anti-inflammatory properties. No studies have been reported on the use of TTO in H2S-induced lung injury in chickens. Therefore, in this study, 240 one-day-old Roman pink laying hens were randomly and equally divided into 3 groups: control group (CON), H2S exposure group (AVG, containing H2S), and TTO treatment group (TTG, containing H2S and 0.02 mL/L TTO) to establish an experimental model of TTO treatment with H2S exposure for a period of 42 d. Hematoxylin and eosin (H&E) staining was used to detect lung histopathology. Gene expression profiles were analyzed using transcriptomics. The underlying mechanism of the amelioration of lung injury by TTO was further revealed by antioxidant enzyme assays and qRT-PCR. The results showed that H2S exposure induced significant gene expression of CYP450s (CYP1B1 and CYP1C1) (P < 0.05), and caused intense oxidative stress, apoptosis and inflammation compared with CON. TTO could reduce ROS production and enhance antioxidant capacity (SOD, CAT, T-AOC, and GSH-PX) by regulating the CYP450s/ROS pathway (P < 0.05). Compared with the control group, the treatment group showed significantly decreased expression of apoptotic (Caspase-8, Caspase-3, Bid and Fas) (P < 0.05) and inflammatory (IL-4, IL-16, NF-κB, TNF-α and IFN-γ) (P < 0.05) factors in the lung. This study revealed that TTO regulated CYP450s/ROS pathway to alleviate H2S-induced lung injury in chickens. These results enrich the theory of the action mechanism of TTO on H2S-exposed chicken lungs and are of great value for the treatment of H2S-exposed animals.


Assuntos
Galinhas , Sistema Enzimático do Citocromo P-450 , Sulfeto de Hidrogênio , Pulmão , Estresse Oxidativo , Óleo de Melaleuca , Animais , Sulfeto de Hidrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Óleo de Melaleuca/farmacologia , Óleo de Melaleuca/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Feminino , Espécies Reativas de Oxigênio/metabolismo , Doenças das Aves Domésticas/induzido quimicamente , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Proteínas Aviárias/metabolismo , Proteínas Aviárias/genética , Distribuição Aleatória , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/veterinária , Lesão Pulmonar/tratamento farmacológico
12.
Biochem Biophys Res Commun ; 722: 150132, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38788354

RESUMO

OBJECTIVE: The present study aims to investigate the protective potential of salidroside in both lung ischemia/reperfusion injury (LIRI) mice model and cell hypoxia/reoxygenation (H/R)model and the involvement of ferroptosis and JAK2/STAT3 pathway. MATERIALS AND METHODS: After we established the IR-induced lung injury model in mice, we administered salidroside and the ferroptosis inhibitor, ferrostatin-1, then assessed the lung tissue injury, ferroptosis (levels of reactive oxygen species level, malondialdehyde and glutathione), and inflammation in lung tissues. The levels of ferroptosis-related proteins (glutathione peroxidase 4, fibroblast-specific protein 1, solute carrier family 1 member 5 and glutaminase 2) in the lung tissue were measured with Western blotting. Next, BEAS-2B cells were used to establish an H/R cell model and treated with salidroside or ferrostatin-1 before the cell viability and the levels of lactate dehydrogenase (LDH), inflammatory factor, ferroptosis-related proteins were measured. The activation of the JAK2/STAT3 signaling pathway was measured with Western blotting, then its role was confirmed with STAT3 knockdown. RESULTS: Remarkably, salidroside was found to alleviate ferroptosis, inflammation, and lung injury in LIRI mice and the cell injury in H/R cell model. Severe ferroptosis were observed in LIRI mice models and H/R-induced BEAS-2B cells, which was alleviated by salidroside. Furthermore, salidroside could inhibit JAK2/STAT3 activation induced by LIRI. STAT3 knockdown could enhance the effect of salidroside treatment on H/R-induced cell damage and ferroptosis in vitro. CONCLUSIONS: Salidroside inhibits ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signaling pathway.


Assuntos
Ferroptose , Glucosídeos , Janus Quinase 2 , Fenóis , Traumatismo por Reperfusão , Fator de Transcrição STAT3 , Transdução de Sinais , Fenóis/farmacologia , Fenóis/uso terapêutico , Animais , Ferroptose/efeitos dos fármacos , Janus Quinase 2/metabolismo , Glucosídeos/farmacologia , Fator de Transcrição STAT3/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos , Humanos , Camundongos Endogâmicos C57BL , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Linhagem Celular , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/etiologia
13.
Free Radic Biol Med ; 220: 179-191, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704053

RESUMO

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.


Assuntos
Atorvastatina , Modelos Animais de Doenças , Armadilhas Extracelulares , Imipenem , NADPH Oxidase 2 , Sepse , Animais , Atorvastatina/farmacologia , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Sepse/tratamento farmacológico , Sepse/metabolismo , Sepse/complicações , Sepse/patologia , Camundongos , Imipenem/farmacologia , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/patologia , Lesão Pulmonar/metabolismo , Masculino , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Transdução de Sinais/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Quimioterapia Combinada
14.
Clin Respir J ; 18(5): e13776, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38778673

RESUMO

This systematic review aimed to summarize the available data on the treatment of pulmonary contusions with exogenous surfactants, determine whether this treatment benefits patients with severe pulmonary contusions, and evaluate the optimal type of surfactant, method of administration, and drug concentration. Three databases (MEDline, Scopus, and Web of Science) were searched using the following keywords: pulmonary surfactant, surface-active agents, exogenous surfactant, pulmonary contusion, and lung contusion for articles published between 1945 and February 2023, with no language restrictions. Four reviewers independently rated the studies for inclusion, and the other four reviewers resolved conflicts. Of the 100 articles screened, six articles were included in the review. Owing to the limited number of papers on this topic, various types of studies were included (two clinical studies, two experiments, and two case reports). In all the studies, surfactant administration improved the selected ventilation parameters. The most frequently used type of surfactant was Curosurf® in the concentration of 25 mg/kg of ideal body weight. In most studies, the administration of a surfactant by bronchoscopy into the segmental bronchi was the preferable way of administration. In both clinical studies, patients who received surfactants required shorter ventilation times. The administration of exogenous surfactants improved ventilatory parameters and, thus, reduced the need for less aggressive artificial lung ventilation and ventilation days. The animal-derived surfactant Curosurf® seems to be the most suitable substance; however, the ideal concentration remains unclear. The ideal route of administration involves a bronchoscope in the segmental bronchi.


Assuntos
Contusões , Lesão Pulmonar , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório , Humanos , Surfactantes Pulmonares/administração & dosagem , Surfactantes Pulmonares/uso terapêutico , Contusões/tratamento farmacológico , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Animais , Respiração Artificial/métodos , Resultado do Tratamento , Broncoscopia/métodos
15.
Int J Antimicrob Agents ; 64(1): 107180, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38649034

RESUMO

OBJECTIVE: The timing and dosing of antimicrobial therapy are key in the treatment of pneumonia in critically ill patients. It is uncertain whether the presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. The effects of lung inflammation and injury on tissue penetration of two antimicrobial drugs commonly used for pneumonia were determined in an established model of unilateral lung injury. METHODS: Unilateral lung injury was induced in the left lung of 13 healthy pigs through cyclic rinsing; the right healthy lung served as control. Infusions of meropenem and vancomycin were administered and concentrations of these drugs in lung tissue, blood, and epithelial lining fluid (ELF) were compared over a period of 6 h. RESULTS: Median vancomycin lung tissue concentrations and penetration ratio were higher in inflamed and injured lungs compared with uninflamed and uninjured lungs (AUC0-6h: P = 0.003 and AUCdialysate/AUCplasma ratio: P = 0.003), resulting in higher AUC0-24/MIC. Median meropenem lung tissue concentrations and penetration ratio in inflamed and injured lungs did not differ from that in uninflamed and uninjured lungs (AUC0-6: P = 0.094 and AUCdialysate/AUCplasma ratio: P = 0.173). The penetration ratio for both vancomycin and meropenem into ELF was similar in injured and uninjured lungs. CONCLUSION: Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not identify the impact of inflammation and injury.


Assuntos
Antibacterianos , Modelos Animais de Doenças , Lesão Pulmonar , Pulmão , Meropeném , Vancomicina , Animais , Meropeném/farmacocinética , Meropeném/administração & dosagem , Vancomicina/farmacocinética , Vancomicina/administração & dosagem , Suínos , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Pulmão/metabolismo , Lesão Pulmonar/tratamento farmacológico , Pneumonia/tratamento farmacológico , Feminino , Testes de Sensibilidade Microbiana
16.
BMC Pulm Med ; 24(1): 207, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671448

RESUMO

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.


Assuntos
Gasderminas , Pulmão , Piroptose , Quinuclidinas , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Ratos , Quinuclidinas/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Superóxido Dismutase/metabolismo , Peroxidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Caspase 1/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo
17.
Ecotoxicol Environ Saf ; 277: 116364, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657461

RESUMO

The purpose of this study was to investigate the effect of Treg/Th1 imbalance in cadmium-induced lung injury and the potential protective effect of astilbin against cadmium-induced lung injury in chicken. Cadmium exposure significantly decreased T-AOC and GSH-Px levels and SOD activity in the chicken lung tissues. In contrast, it significantly increased the MDA and NO levels. These results indicate that cadmium triggers oxidative stress in lungs. Histopathological analysis revealed that cadmium exposure further induced infiltration of lymphocytes in the chicken lungs, indicating that cadmium causes pulmonary damage. Further analysis revealed that cadmium decreased the expression of IL-4 and IL-10 but increased those of IL-17, Foxp3, TNF-α, and TGF-ß, indicating that the exposure of cadmium induced the imbalance of Treg/Th1. Moreover, cadmium adversely affected chicken lung function by activating the NF-kB pathway and inducing expression of genes downstream to these pathways (COX-2, iNOS), associated with inflammatory injury in the lung tissue. Astilbin reduced cadmium-induced oxidative stress and inflammation in the lungs by increasing antioxidant enzyme activities and restoring Treg/Th1 balance. In conclusion, our results suggest that astilbin treatment alleviated the effects of cadmium-mediated lung injury in chickens by restoring the Treg/Th1 balance.


Assuntos
Cádmio , Galinhas , Flavonóis , Lesão Pulmonar , Pulmão , Estresse Oxidativo , Transdução de Sinais , Linfócitos T Reguladores , Animais , Cádmio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Flavonóis/farmacologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico
19.
Food Funct ; 15(7): 3411-3419, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38470815

RESUMO

Tetrabromobisphenol A (TBBPA) is a global pollutant. When TBBPA is absorbed by the body through various routes, it can have a wide range of harmful effects on the body. Green tea polyphenols (GTPs) can act as antioxidants, resisting the toxic effects of TBBPA on animals. The effects and mechanisms of GTP and TBBPA on oxidative stress, inflammation and apoptosis in the mouse lung are unknown. Therefore, we established in vivo and in vitro models of TBBPA exposure and GTP antagonism using C57 mice and A549 cells and examined the expression of factors related to oxidative stress, autophagy, inflammation and apoptosis. The results of the study showed that the increase in reactive oxygen species (ROS) levels after TBBPA exposure decreased the expression of autophagy-related factors Beclin1, LC3-II, ATG3, ATG5, ATG7 and ATG12 and increased the expression of p62; oxidative stress inhibits autophagy levels. The increased expression of the pro-inflammatory factors IL-1ß, IL-6 and TNF-α decreased the expression of the anti-inflammatory factor IL-10 and activation of the NF-κB p65/TNF-α pathway. The increased expression of Bax, caspase-3, caspase-7 and caspase-9 and the decreased expression of Bcl-2 activate apoptosis-related pathways. The addition of GTP attenuated oxidative stress levels, restored autophagy inhibition and reduced the inflammation and apoptosis levels. Our results suggest that GTP can attenuate the toxic effects of TBBPA by modulating ROS, reducing oxidative stress levels, increasing autophagy and attenuating inflammation and apoptosis in mouse lung and A549 cells. These results provide fundamental information for exploring the antioxidant mechanism of GTP and further for studying the toxic effects of TBBPA.


Assuntos
Lesão Pulmonar , NF-kappa B , Bifenil Polibromatos , Camundongos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Estresse Oxidativo , Apoptose , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Polifenóis/farmacologia , Chá , Guanosina Trifosfato/metabolismo , Guanosina Trifosfato/farmacologia
20.
BMC Mol Cell Biol ; 25(1): 7, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486170

RESUMO

BACKGROUND: In recent years, the role of autophagy has been highlighted in the pathogenesis of diabetes and inflammatory lung diseases. In this study, using a diabetic model of mice, we investigated the expression of autophagy-related genes in the lung tissues following melatonin administration. RESULTS: Data showed histopathological remodeling in lung tissues of the D group coincided with an elevated level of IL-6, Becline-1, LC3, and P62 compared to the control group (p < 0.05). After melatonin treatment, histopathological remodeling was improved D + Mel group. In addition, expression levels of IL-6, Becline-1, LC3, and P62 were decreased in D + Mel compared to D group (P < 0.05). Statistically significant differences were not obtained between Mel group and C group (p > 0.05). CONCLUSION: Our results showed that melatonin injection can be effective in the amelioration of lung injury in diabetic mice presumably by modulating autophagy-related genes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Lesão Pulmonar , Melatonina , Animais , Camundongos , Lesão Pulmonar/tratamento farmacológico , Melatonina/farmacologia , Melatonina/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Interleucina-6 , Autofagia
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