[Show abstract][Hide abstract] ABSTRACT: Lipopolysaccharide (LPS), also called endotoxin, is the important pathogen of acute lung injury (ALI), which is a clinical syndrome that still lacks effective therapeutic medicine. Rutin belongs to vitamin P and possesses various beneficial effects. In this study, we investigate the potential protective effects and the mechanisms of rutin on LPS-induced ALI. Pre-administration with rutin inhibited LPS-induced arterial blood gas exchange and neutrophils infiltration in the lungs. LPS-induced expression of macrophage inflammatory protein (MIP)-2 and activation of matrix metalloproteinase (MMP)-9 were suppressed by rutin. In addition, the inhibitory concentration of rutin on phosphorylation of Akt was similar as MIP-2 expression and MMP-9 activation. In conclusion, rutin is a potential protective agent for ALI via suppressing the blood gas exchange and neutrophil infiltration. The mechanism of rutin is down-regulation of MIP-2 expression and MMP-9 activation through inhibition of Akt phosphorylation.
[Show abstract][Hide abstract] ABSTRACT: Acute lung injury (ALI) is a serious disease with unacceptably high mortality and morbidity rates. Up to now, no effective therapeutic strategy for ALI has been established. Rutin, quercetin-3-rhamnosyl glucoside, expresses a wide range of biological activities and pharmacological effects, such as anti-inflammatory, anti-hypertensive, anti-carcinogenic, vasoprotective, and cardioprotective activities. Pretreatment with rutin not only inhibited histolopatholgical changes in lung tissues but also infiltration of polymorphonuclear granulocytes (PMNs) into bronchoalveolar lavage fuild (BALF) in LPS-induced ALI. In addition, LPS-induced inflammatory responses, including increased secretion of proinflammatory cytokines and lipid peroxidation, were inhibited by rutin in a concentration-dependent manner. Furthermore, rutin suppressed phosphorylation of NF-κB and MAPK, and degradation of IκB, a NF-κB inhibitor. Decreased activities of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and hemeoxygenase (HO)-1 caused by LPS were reversed by rutin. At the same time, we found that ALI amelioration by chelation of extracellular metal ions with rutin is more efficacious than with deferoxamine. These results indicated that the protective mechanism of rutin is by inhibition of MAPK-NFκB activation and up-regulation of antioxidative enzymes.
Free Radical Biology and Medicine 01/2014; · 5.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Wogonin is a flavonoid compound which exhibits antioxidation, anti-inflammation, neuroprotection, and antitumorgenesis functions. However, the mechanism of how wogonin reduces proinflammatory cytokine generation in activated microglia is unclear. At present, we found wogonin inhibited lipopolysaccharide (LPS)-/interferon-γ (INF-γ)-induced generation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Wogonin exhibited parallel inhibition on LPS-/INF-γ-induced expression of IL-6 and TNF-α messenger RNA at the same concentration range. LPS-/INF-γ-induced phosphorylation of signal transduction and transcription 1 and 3 (STAT1/3) were also inhibited by wogonin. Although wogonin expressed only weak inhibitory effect on LPS-/INF-γ-induced phosphorylation of Janus kinase-2 (Jak-2) and tyrosine kinase (Tyk)-2, it significantly attenuated the phosphorylation of Jak-1 and Jak-3. These results indicated that the blockade of IL-6 and TNF-α production by wogonin in LPS-/INF-γ-stimulated BV2 microglial cells was attributed mainly to the interference in Jak-1/-3-STAT1/3 signaling pathway.
Toxicology and Industrial Health 04/2013; · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute lung injury (ALI) presents high mortality and morbidity clinically and by far no effective preventive strategy has been established. Extract of Ginkgo biloba leaves, EGb 761, is a complex mixture that possesses several clinical beneficial effects such as anti-oxidation, anti-inflammation, anti-tumor, and cardioprotective property. With EGb 761 pretreatment, both lipopolysaccharide (LPS)-induced protein leakage and neutrophil infiltration, and LPS-induced inflammatory responses including increased myeloperoxidase (MPO) activity, lipid peroxidation, and metalloproteinase (MMP)-9 activity, were inhibited; LPS-suppressed activation of antioxidative enzymes (AOE) were reversed; and not only the phosphorylation of NF-κB but also the degradation of its inhibitor, IκB, were suppressed. These results suggested that the protection mechanism of EGb 761 is by inhibition of NFκB activation, possibly via the up-regulation of antioxidative enzymes. More studies are needed to further evaluate whether EGb 761 is a suitable candidate as an effective dietary strategy to reduce the incidence of endotoxin-induced ALI.
Phytomedicine: international journal of phytotherapy and phytopharmacology 12/2012; · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The toxicity of dental materials has raised public concern over the past years. One of the most commonly used methacrylic monomers for building the three-dimensional structure of the dental resin composites is 2,2-bis[4-(acryloxypropoxy)phenyl]propane (BAPP). The purpose of this study is to evaluate the potential toxicological implication of BAPP on human gingival fibroblasts (HGFs). Flow cytometric, fluorometric, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assays were used to detect the mode of cell death, caspase activities, and cell viability, respectively. In addition, alkaline single-cell gel electrophoresis (COMET) and cytokinesis block micronucleus (MN) assays were applied to evaluate the genotoxicity. According to the results BAPP demonstrated a cytotoxic effect on HGFs in a dose- and time-dependent manner. With increasing concentrations of BAPP, the mode of cell death shifted from apoptosis to necrosis, and the activities of caspases 3, 8, and 9 were also significantly induced. Moreover, a dose-related increase in the number of micronucleus and DNA strand breaks hinted at the expression of genotoxicity by BAPP. In conclusion, the results gathered from this study had demonstrated that BAPP-induced cytotoxicity and genotoxicity on HGFs were mediated by DNA damage and the activation of caspases 3, 8, and 9.
Toxicology and Industrial Health 10/2012; · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute lung injury (ALI), instilled by lipopolysaccharide (LPS), is a severe illness with excessive mortality and has no specific treatment strategy. Luteolin is an anti-inflammatory flavonoid and widely distributed in the plants. Pretreatment with luteolin inhibited LPS-induced histological changes of ALI and lung tissue edema. In addition, LPS-induced inflammatory responses, including increased vascular permeability, tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), were also reduced by luteolin in a concentration-dependent manner. Furthermore, luteolin suppressed activation of NFκB and its upstream molecular factor, Akt. These results suggest that the protection mechanism of luteolin is by inhibition of NFκB activation possibly via Akt.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:383608. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chinese hamster ovary (CHO) cells, its lung fibroblasts (V79), and human lymphocytes are routinely used in in vitro cytogenetic assays, which include micronuclei (MN), sister chromatid exchange (SCE), and chromosome aberration (CA) assays. Mitomycin C (MMC), a DNA cross-link alkylating agent, is both an anticancer medicine and a carcinogen. To study the differential representative values of cell types in MMC-treated cytogenetic assays and its upstream factor, cysteine aspartic acid-specific protease (caspase)-3. Among the chosen cell types, lymphocytes expressed the highest sensitivity in all three MMC-induced assays, whereas CHO and V79 showed varied sensitivity in different assays. In MN assay, the sensitivity of CHO is higher than or equal to V79; in SCE assay, the sensitivity of CHO is the same as V79; and in CA assay, the sensitivity of CHO is higher than V79. In-depth analysis of CA revealed that in chromatid breaks and dicentrics formation, lymphocyte was the most sensitive of all and CHO was more sensitive than V79; and in acentrics and interchanges formation, lymphocyte was much more sensitive than the others. Furthermore, we found caspase-3 activity plays an important role in MMC-induced cytogenetic assays, with MMC-induced caspase-3 activity resulting in more sensitivity in lymphocytes than in CHO and V79. Based on these findings, lymphocyte will make a suitable predictive or representative control reference in cytogenetic assays and caspase-3 activity with its high specificity, positive predictive value, and sensitivity.
Toxicology and Industrial Health 07/2011; 28(2):174-80. · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acute lung injury (ALI) in critically ill patients remains the leading cause of mortality and morbidity. Lipopolysaccharide (LPS) is a key mediator of lung injury. This study investigates the protective effects and mechanisms of luteolin in intratracheal instillation of LPS (100μg)-induced ALI in mice. Pretreatment of mice with 70μmol/kg luteolin significantly restores LPS-induced decrease in oxygen pressure and increase in carbon dioxide in arterial blood. The histopathological study established 70μmol/kg luteolin pretreatment markedly attenuates lung histopathological changes, such as haemorrhaging, interstitial edema, and infiltration of polymorphonuclear neutrophils (PMNs) into the lung parenchyma and alveolar spaces. Sufficient evidence for luteolin (35 and 70μmol/kg) suppresses activation and infiltration of PMNs is obtained in expression of surface marker CD11b and Ly6G on cells in bronchoalveolar lavage fluid (BALF) cells and myeloperoxidase activity in lung tissue. Furthermore, luteolin reduces the activity of catalase and superoxide dismutase, and the level of oxidative damage, and lipid peroxidation, in lung tissue. In addition, the secretion of TNF-α, KC, and ICAM-1 in the BALF after LPS challenge are also inhibited by luteolin. Moreover, luteolin reduced LPS-induced activation of MAPK and NFκB pathways. Therefore, luteolin is a potential protective antagonists for LPS-induced ALI in mice.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 07/2011; 49(10):2660-6. · 2.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Three-dimensional computed tomography (3D-CT) not only allows accurate preoperative delineation of the lesions but also provides precise pathomechanic diagnosis for planning the most effective treatment to avoid respiratory compromise. In a 10-month-old baby girl, who was ventilator-dependent after successful correction of double outlet right ventricle (DORV), flexible fiberoptic bronchoscopy (FFB) revealed the new formation of postoperative airway obstruction over the right main bronchus (RMB) and obstructed right tracheal bronchus (RTB). 3D-CT demonstrated tracheobronchial obstruction (TBO) was caused by the dilated ascending aorta (AAo) and right pulmonary artery (RPA). Sequential treatments including artery pexy of AAo and RPA and balloon dilatation (BD) of the stenotic RTB and RMB had successfully restored the airway patency. The patient was successfully weaned from ventilator 2 days after treatments and has shown no respiratory difficulty thus far. Thus, the impact of preoperative 3D-CT on planning treatment cannot be emphasized.