Pulmonary implications of acetaminophen exposures independent of hepatic toxicity

2021 ◽  
Author(s):  
Evgenia Dobrinskikh ◽  
Saif Al-Juboori ◽  
Miguel Zarate ◽  
Lijun Zheng ◽  
Robyn de Dios ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Hepatic Injury ◽  
Lavage Fluid ◽  
Metabolic Changes ◽  
High Dose ◽  
Alveolar Wall ◽  
Pulmonary Injury ◽  
Hepatic Toxicity ◽  
Adult Mice ◽  
Dose Dependent

Both pre-clinical and clinical studies have demonstrated that exposures to acetaminophen (APAP) at levels that cause hepatic injury cause pulmonary injury as well. However, whether exposures that do not result in hepatic injury have acute pulmonary implications is unknown. Thus, we sought to determine the how APAP exposures at levels that do not result in significant hepatic injury impact the mature lung. Adult male ICR mice (8-12 weeks) were exposed to a dose of APAP known to cause hepatotoxicity in adult mice (280 mg/kg, IP), as well as a lower dose previously reported to not cause hepatic injury (140 mg/kg, IP). We confirm that the lower dose exposures did not result in significant hepatic injury. However, like high dose, lower exposure resulted in increased cellular content of the bronchoalveolar lavage fluid, and induced a pro-inflammatory pulmonary transcriptome. Both the lower and higher dose exposures resulted in measurable changes in lung morphometrics, with the lower dose exposure causing alveolar wall thinning. Using RNAScope, we were able to detect dose-dependent, APAP-induced pulmonary Cyp2e1expression. Finally, using FLIM we determined that both APAP exposures resulted in acute pulmonary metabolic changes consistent with mitochondrial overload in lower dose and a shift to glycolysis at a high dose. Our findings demonstrate that APAP exposures that do not cause significant hepatic injury result in acute inflammatory, morphometric and metabolic changes in the mature lung. These previously unreported findings may help explain the potential relationship between APAP exposures and pulmonary-related morbidity.

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs

1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  
Keyword(s):  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Neurokinin A ◽  
Dependent Manner ◽  
C Fiber ◽  
Dose Dependent

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

scholarly journals Actinomyces graevenitziiPulmonary Abscess Mimicking Tuberculosis in a Healthy Young Man

2014 ◽  
Vol 21 (6) ◽  
pp. e75-e77 ◽  
Author(s):  
Smaranda Gliga ◽  
Mathilde Devaux ◽  
Marine Gosset Woimant ◽  
Dominique Mompoint ◽  
Christian Perronne ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Clinical Samples ◽  
High Dose ◽  
Pulmonary Actinomycosis ◽  
History Of ◽  
Right Lobe

Pulmonary actinomycosis is a rare disease that is often misdiag-nosed as tuberculosis or lung cancer.Actinomyces graevenitziiis a relatively new recognizedActinomycesspecies isolated from various clinical samples. The authors report a case of pulmonary actinomycosis caused byA graevenitzii. A computed tomography examination revealed an excavated consolidation in the middle right lobe of a previously healthy young man who presented with a long history of moderate cough. Cultures of the bronchoalveolar lavage fluid confirmed the diagnosis of pulmonary abscess caused byA gravenitzii. At the three-month follow-up consultation and, after six weeks of high-dose amoxicillin, the pulmonary lesion had completely disappeared.

scholarly journals Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17

2020 ◽  
Author(s):  
Qiancheng Luo ◽  
Rui Liu ◽  
Guorong Liu ◽  
Min Hang ◽  
Guo Chen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Surface Expression ◽  
Pulmonary Injury ◽  
Protective Mechanisms ◽  
Tnf Α ◽  
G Protein Coupled ◽  
Very High ◽  
Masson Staining

Abstract BackgroundSepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist antiplatelet drug.MethodsIn our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using mouse models.ResultsTdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1β, IL-6, and TNF-α. Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 ༈GPR17༉induced by CLP. Conclusion: Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

scholarly journals Anti-inflammatory Activity of Lefamulin in a Lipopolysaccharide-Induced Lung Neutrophilia Model

2020 ◽  
Author(s):  
Michael Hafner ◽  
Susanne Paukner ◽  
Wolfgang W. Wicha ◽  
Boška Hrvačić ◽  
Steven P. Gelone
Keyword(s):  
Bacterial Pneumonia ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Inflammatory Activity ◽  
Free Base ◽  
Cell Counts ◽  
Oral Dexamethasone ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Neutrophil Cell

ABSTRACTLefamulin is a novel pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia. This study demonstrated anti-inflammatory activity of lefamulin in a murine lipopolysaccharide-induced lung neutrophilia model. Pretreatment of mice at clinically relevant lefamulin subcutaneous doses (35, 70, 140 mg/kg [free base]) followed by intranasal lipopolysaccharide challenge (5 μg/50 μL/mouse) demonstrated significant, dose-dependent reductions in total and neutrophil cell counts in bronchoalveolar lavage fluid samples, with reductions comparable to oral dexamethasone (0.5 mg/kg) pretreatment.

Depression of DNA synthesis in the thymus of zinc-treated adult mice

1983 ◽  
Vol 48 (10) ◽  
pp. 3020-3023
Author(s):  
Alois Čihák ◽  
Milagros Carcia Mesa ◽  
Hideo Inoue
Keyword(s):  
Dna Synthesis ◽  
High Dose ◽  
Adult Mice ◽  
Dose Dependent ◽  
Zn Ions

Zn-ions in a high dose affect the uptake of thymidine into thymus DNA. The depression of DNA synthesis in the thymus of zinc-treated mice is dose-dependent and is more pronounced in adult than in young animals.

The C/A(−18) polymorphism in the surfactant protein B gene influences transcription and protein levels of surfactant protein B

2007 ◽  
Vol 292 (2) ◽  
pp. L448-L453 ◽  
Author(s):  
Wendy K. Steagall ◽  
Jing-Ping Lin ◽  
Joel Moss
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Normal Volunteer ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Transcriptional Analysis ◽  
Regulatory Function ◽  
Adult Mice ◽  
Surfactant Protein B ◽  
Protein B

Surfactant protein B (SP-B) is an essential component of surfactant that promotes adsorption and spreading of surfactant phospholipids and stabilizes the phospholipid monolayer. SP-B is essential for respiratory function in newborn humans and mice; adult mice with levels of SP-B below 25% of wild-type develop fatal respiratory distress syndrome. A potential regulatory function of the C/A(−18) single nucleotide polymorphism (SNP) in the promoter of the SP-B gene was examined. Transcriptional analysis and ELISA on bronchoalveolar lavage fluid revealed that the presence of the C allele correlated with more SP-B promoter activity and protein. There was approximately threefold difference in amounts of SP-B in bronchoalveolar lavage fluid from CA(−18) and AA(−18) individuals. By EMSA, Sp1 bound more tightly to the C allele sequence than to the A allele sequence, perhaps accounting for the differences in transcription. Genotyping of a normal volunteer population showed ∼31% of the population were AA homozygotes, suggesting that these individuals produce less SP-B. Differences in amounts of SP-B resulting from the promoter SNP could affect the clinical presentation of pulmonary disease.

scholarly journals Ozone-induced airway hyperresponsiveness is reduced in immature mice

2002 ◽  
Vol 92 (3) ◽  
pp. 1019-1028 ◽  
Author(s):  
S. A. Shore ◽  
R. A. Johnston ◽  
I. N. Schwartzman ◽  
D. Chism ◽  
G. G. Krishna Murthy
Keyword(s):  
Body Weight ◽  
Airway Hyperresponsiveness ◽  
Bronchoalveolar Lavage Fluid ◽  
Minute Ventilation ◽  
Lavage Fluid ◽  
Adult Mice ◽  
Inflammatory Protein ◽  
Age Related ◽  
Old Mice ◽  
Macrophage Inflammatory Protein

During ozone (O3) exposure, adult mice decrease their minute ventilation (V˙e). To determine whether there are age-related differences in the ventilatory response to O3, A/J mice, aged 2, 4, 8, or 12 wk, were exposed to O3(0.3–3.0 parts/million for 3 h) in nose-only exposure plethysmographs. Baseline V˙e normalized for body weight (V˙e/g) decreased with increasing age, consistent with the higher metabolic rates of younger animals. O3 caused a concentration-related decrease inV˙e in mice of all ages, but the response was significantly less in 2-wk-old than in older mice. The increased baseline V˙e/g and smaller decrements inV˙e induced by O3 in immature mice resulted in an inhaled dose of O3 normalized for body weight that was three to four times higher than in adult mice. O3 exposure caused a dose-related increase in airway responsiveness in 8- and 12-wk-old mice but did not cause airway hyperresponsiveness at any dose in either 2- or 4-wk-old mice, although higher inhaled doses of O3 normalized for body weight were delivered to these younger animals. Interleukin-6 and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid were also increased in 8-wk-old compared with 2-wk-old mice exposed to O3. The results suggest that immature mice are less sensitive than adult mice to O3, at least in terms of the ability of O3 to induce airway hyperresponsiveness and promote release of certain cytokines.

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