ABSTRACT
Aim To investigate the effect of broneol on acute lung injury(ALI) induced by lipopolysaccharide (LPS). Methods Male C57 mice were randomly di-vided into saline group, model group, broneol group and dexamethasone group, then the ALI mouse model was induced by instilling intratracheally with LPS. The levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6) and keratinocyte-de-rived cytokine (KC) were measured at 6h, 12h and 24h after instillation of LPS, and the pathological changes of lung were observed. Mice alveolar macro-phages (MHS) and epithelial cells (MLE-12) were stimulated by LPS. After the stimulation of 1h, 3h, 6h,9h, 12h, 24h, the levels of TNF-α and IL-6 in MHS cells and the contents of KC and macrophage in-flammatory protein-2 (MIP-2) in MLE-12 cells were measured. Results Broneol could inhibit the secre-tion of TNF-α,KC and IL-1β;the early effect of bro-neol on IL-6 was not obvious,but the later effect after the treatment of 24 hours was obvious. After LPS instil-lation 6h and 12h,Broneol could significantly improve lung tissue pathological changes. Broneol had no effect on TNF-α secretion of MHS cells, but it obviously af-fected IL-6 secretion in the later stage. In addition, broneol significantly inhibited KC and MIP2 secretion in MLE-12 cells at the later stage of LPS stimulation. Conclusions Broneol can protect LPS-induced acute lung injury. The mechanism may be related to the inhi-bition of the release of inflammatory factors,the activa-tion of inflammatory cells and the aggregation of neutro-phils.
ABSTRACT
cAMP-specific phosphodiesterase type 4 (PDE4) is one of the hot targets for treatment of inflammatory diseases. PDE4 inhibitors can suppress inflammation by increasing the concentration of cAMP in inflammatory cells. The efficacy and safety evaluations of several PDE4 inhibitors are currently carried on in clinical trials, for example GSK256066 in asthma, roflumilast and GSK256066 in chronic obstructive pulmonary disease, tetomilast in inflammatory bowel disease, and apremilast in dermatitis and arthritis etc. This article reviews the recent progress on PDE4-targeted therapy for inflammatory diseases.
Subject(s)
Humans , Aminopyridines , Pharmacology , Aminoquinolines , Pharmacology , Arthritis , Drug Therapy , Asthma , Drug Therapy , Benzamides , Pharmacology , Cyclopropanes , Pharmacology , Dermatitis , Drug Therapy , Inflammation , Drug Therapy , Inflammatory Bowel Diseases , Drug Therapy , Phosphodiesterase 4 Inhibitors , Pharmacology , Pulmonary Disease, Chronic Obstructive , Drug Therapy , Sulfones , Pharmacology , Thalidomide , Pharmacology , Thiazoles , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To develop a mouse model of acute lung injury induced by cigarette smoke (CS) and to investigate inflammatory changes with the model.</p><p><b>METHODS</b>ICR mice exposed to CS for 20-min, 3/d. Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested at d 0, d 1, d 3 and d 7 after CS exposure. Neutrophil count in BAFL, TNF-alpha and MMP-12 levels, the activity of MPO in lung tissue were determined.</p><p><b>RESULT</b>Neutrophil count in BALF, MMP-12 and MPO levels in lung tissue were increased after CS exposure in a time-dependent manner with a peak at d3. TNF-alpha level sharply increased at d1, and remained high level until d7.</p><p><b>CONCLUSION</b>ICR mice are tolerant and sensitive to CS exposure, which may be used as an appropriate animal model for acute lung injury induced by cigarette smoke.</p>
Subject(s)
Animals , Male , Mice , Acute Lung Injury , Pathology , Bronchoalveolar Lavage Fluid , Cell Biology , Disease Models, Animal , Matrix Metalloproteinase 12 , Metabolism , Mice, Inbred ICR , Smoke , Tobacco , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
The aim of this study is to investigate the effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide (LPS) -induced acute lung injury (ALI) and its anti-inflammatory mechanism in mice. All male ICR mice were randomly divided into six groups: LPS group; control group; MAG 3, 10, and 30 mg x kg(-1) groups; and dexamethasone (DXM) 5 mg x kg(-1) group. Lung dry weight and wet weight percentage and permeability were detected. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and lung tissues was detected by cell count and morphological analysis. The levels of TNF-alpha and IL-10 in lung were detected by ELISA. MPO activity was determined followed the specification. MAG induced a decrease in lung wet weight/dry weight ratio, and significantly decreased in total leucocyte number and neutrophil percentage in the BALF, and MPO activity of lung in a dose-dependent manner. Importantly, It could up-regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue of ALI mice. These results suggested that the protective effect of MAG in mice on LPS induced ALI was associated with the regulation of TNF-alpha/IL-10 balance, and MAG maybe a potentially treatment for ALI/ARDS.
Subject(s)
Animals , Male , Mice , Acute Lung Injury , Metabolism , Pathology , Anti-Inflammatory Agents , Pharmacology , Bronchoalveolar Lavage Fluid , Cell Biology , Glycyrrhizic Acid , Pharmacology , Interleukin-10 , Metabolism , Leukocyte Count , Lipopolysaccharides , Lung , Pathology , Mice, Inbred ICR , Neutrophils , Pathology , Organ Size , Peroxidase , Metabolism , Protective Agents , Pharmacology , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effect of levobupivacaine and bupivacaine on the contractility of isolated uterine muscle strips from pregnant and non-pregnant female rats.</p><p><b>METHODS</b>Full-thick myometrial strips were prepared from 18- to 21-day pregnant (n=8) and non-pregnant rats (n=7). After contractions became regular, strips were exposed to cumulative concentrations of the two drugs from 10(-8) to 10(-4) mol/L, amplitude and frequency of the uterine contraction was recorded.</p><p><b>RESULTS</b>Two local anesthetics caused a concentration dependent inhibition on contractility of myometrial strips from pregnant and non-pregnant rats. In the myometrium from non-pregnant rats, -logIC(50) of levobupivacaine and bupivacaine were 4.85 and 4.25 respectively. In the myometrium from pregnant rats, similar concentrations of levobupivacaine and bupivacaine were observed, -logIC(50) were 2.7 and 2.9 respectively. Levobupivacaine produced an increase in amplitude of contractions, while bupivacaine showed an increased trend in frequency.</p><p><b>CONCLUSION</b>These results demonstrate that levobupivacaine and bupivacaine may inhibit myometrium contractility. The inhibitory effect of levobupivacaine or bupivacaine is not enhanced by gestation in rat. Levobupivacaine may have more positive influence than bupivacaine in pregnant myometrium.</p>
Subject(s)
Animals , Female , Pregnancy , Rats , Anesthetics, Local , Pharmacology , Bupivacaine , Blood , Pharmacology , Dose-Response Relationship, Drug , In Vitro Techniques , Rats, Sprague-Dawley , Uterine ContractionABSTRACT
<p><b>OBJECTIVE</b>To study the effects of very late antigen(VLA) antagonist BIO-1211 on eosinophil chemotaxis, recruitment and mediator release.</p><p><b>METHODS</b>Eosinophil chemotaxis was induced by platelet activating factor(PAF) in vitro and eosinophil recruitment and release were determined in vivo.</p><p><b>RESULT</b>VLA antagonist BIO-1211 inhibited eosinophil chemotaxis induced by PAF. The inhibitory rates at 4x10(-11), 4x10(-10), 4x10(-9) mol x L(-1) were 24.9%, 29.9%, and 31.3%, respectively. Pretreatment by BIO-1211 1, 3 and 10 mg x kg(-1) intraperitoneally inhibited the recruitment of eosinophils in PAF in the rat induced by Sephadex in a dose dependent manner. Inhibitory rates were 60.3%, 68.9%, and 72.9%(P<0.05), respectively. BIO-1211 did not inhibit eosinophil peroxidase(EPO) release from eosinophils.</p><p><b>CONCLUSION</b>BIO-1211 inhibits eosinophil chemotaxis and recruitment, alleviates local inflammation, and may represent a new type of drug for allergic diseases.</p>
Subject(s)
Animals , Male , Rats , Cell Movement , Chemotaxis, Leukocyte , Dose-Response Relationship, Drug , Eosinophil Peroxidase , Eosinophils , Physiology , Integrin alpha4beta1 , Physiology , Oligopeptides , Pharmacology , Peroxidases , Bodily Secretions , Platelet Activating Factor , Pharmacology , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To study the effects of polysaccharides of cultured Cryptoporus volvatus(CVPS) on airway hyperresponsiveness of ovalbumin-sensitized rats and to evaluate their mechanisms.</p><p><b>METHODS</b>Polysaccharides A, B (5mg/kg, 20mg/kg) and ketotifen(5mg/kg) or vehicle(same volume of saline) were administrated orally for 10 days in ovalbumin -sensitized rats, methacholine bronchial provocation tests were performed to determine airway hyperresponsiveness. Bronchoalveolar lavage fluid (BALF) and peritoneal lavage fluid were prepared after the animals were challenged by nebulized antigen. The differential white cell count in BALF,and the degranulated mast cell count as well as differential white cell count in peritoneal lavage fluid were performed.</p><p><b>RESULT</b>Polysaccharides markedly inhibited the increased lung resistance and the decreased lung compliance induced by antigen challenge,significantly reduced total cell counts and absolute eosinophil counts in BALF(P<0.05); polysaccharides B was more effective than polysaccharides A. They also inhibited recruitment of inflammatory cells in peritoneal lavage fluid and inhibited the allergen-induced mast cell degranulation.</p><p><b>CONCLUSION</b>Polysaccharides of CVPS inhibit airway hyperresponsiveness by stabilizing mast cell membranes and reducing infiltration and chemotaxis of eosinophils and may be developed as a potential anti-asthmatic drug.</p>