stilbenes and Acute-Lung-Injury

Resveratrol, a natural polyphenolic molecule with several biological activities, is a well recognized anti-oxidant, anti-aging and cancer chemopreventive agent. Moreover, resveratrol anti-inflammatory and antifibrotic properties have been demonstrated both in vitro and in different animal models of inflammatory pathologies, including bowel and liver diseases. We review the evidence of resveratrol protective role in respiratory diseases such as acute lung injury, asthma, chronic obstructive pulmonary disease and lung fibrosis. We conclude that resveratrol and its derivatives may act as a therapeutic agents in respiratory diseases and pertinent clinical trials should be performed.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Asthma; Disease Models, Animal; Fibrosis; Humans; Inflammation; Liver Diseases; Lung; Mice; Pulmonary Disease, Chronic Obstructive; Resveratrol; Stilbenes

Acute lung injury (ALI) is a major pathophysiological problem defined by severe inflammation and acute disease with substantial morbidity and death. It is known that lipopolysaccharide (LPS) induces ALI by causing oxidative stress and inflammation. The goal of this study was to investigate the protective effect of astringin on LPS-induced ALI and probable pathways. Astringin is a stilbenoid, the 3-β-D-glucoside of piceatannol, mainly found in the bark of Picea sitchensis. The findings showed that astringin prevented LPS-induced cellular damage by reducing the generation of oxidative stress in LPS-stimulated A549 lung epithelial cells. Furthermore, astringin extensively decreased the production of inflammatory factors such as TNF-α, IL-1β, and IL-6. In addition, the western blot results revealed that the ability of astringin to reduce oxidative stress and the generation of inflammatory cytokines by inhibiting the ROS-mediated PI3K/AKT/NF-κB pathway could be the reason for its protective effect against LPS-induced ALI. Overall, the results suggest that astringin could be a possible inhibitor of ALI triggered by LPS for pediatric lung injury.

Topics: Acute Lung Injury; Child; Glucosides; Humans; Inflammation; Lipopolysaccharides; Lung; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; Stilbenes

Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI).. This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI.. Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment.. After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE.. PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Lipopolysaccharides; Male; Nuclear Receptor Subfamily 4, Group A, Member 1; Rats; Rats, Sprague-Dawley; Stilbenes

Acute liver injury (ALI) refers to abnormalities in liver function caused by various causes and accompanied by poor prognosis and high mortality. Common predisposing factors for the disease are viral hepatitis, bacteria, alcohol, and certain hepatotoxic drugs. Inflammatory response and oxidative stress are critical for the pathogenesis of ALI. Pterostilbene (Pte), a natural polyphenol product extracted from blueberries and grapes, has been reported that exerted multiple biological activities, including antioxidative, anti-inflammatory, anti-carcinogenic, and anti-apoptotic properties. However, there is very little data showing the hepatoprotective effect of Pte on lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced ALI in mice. In this study, the possible protective effect and potential mechanisms of Pte on ALI are being investigated. It has been found that Pte markedly ameliorates LPS/D-Gal-induced inflammatory infiltration, hemorrhage, and dissociation of the hepatic cord, reducing the myeloperoxidase (MPO) activity in liver tissues and serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in ALI. Pte also inhibits LPS/D-Gal-induced secretion of pro-inflammatory cytokine tumor necrosis factor-a (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β) in liver tissues. Furthermore, the western blot analysis reveals that LPS/D-Gal-activated nuclear factor-kappa B (NF-κB) is significantly inhibited by Pte, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) are upregulated by Pte. In conclusion, our results suggest that Pte exerts anti-inflammatory and antioxidative effects, which might contribute to ameliorating LPS/D-Gal-induced ALI in mice. Pte has the potential to be a preventive hepatoprotective agent.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Blotting, Western; Cytokines; Enzyme-Linked Immunosorbent Assay; Galactosamine; Lipopolysaccharides; Liver; Male; Mice; Mice, Inbred BALB C; Protective Agents; Random Allocation; Real-Time Polymerase Chain Reaction; Stilbenes; Treatment Outcome

Nuclear factor erythroid-2 related factor 2 (Nrf2) is involved in mitigating various oxidative stress- and inflammation-induced diseases, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Isorhapontigenin (ISO), from the Chinese herb Gnetum cleistostachyum, exhibits antioxidant and anti-inflammatory properties. In this study, we explored the protective effects of ISO in ALI and its underlying molecular mechanisms. ISO significantly mitigated ALI by reducing the lung wet/dry weight ratio, protein concentration in the bronchoalveolar lavage fluid (BALF), and the levels of myeloperoxidase and malondialdehyde. ISO also improved the superoxide dismutase and glutathione activity in vivo. Moreover, ISO effectively ameliorated the changes in IL-1β, IL-6, and TNF-α concentrations in BALF, prevented IκB degradation, and inhibited the phosphorylation of NF-κB p65 subunit in lung tissues; furthermore, it enhanced the nuclear translocation of Nrf2 and inhibited IL-1β, IL-6, TNF-α, iNOS, COX-2, and ROS production in lipopolysaccharide-treated RAW264.7 cells. The protective effects of ISO in ALI were significantly reversed in ML385-treated RAW264.7 cells and the mouse model, indicating its role in Nrf2-activation. In conclusion, ISO effectively ameliorated lipopolysaccharide-induced ALI by reducing inflammation and oxidative stress, primarily through activation of Nrf2 signaling.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Cells, Cultured; Humans; Inflammation; Lipopolysaccharides; Mice; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction; Stilbenes

Severe traumatic brain injury (sTBI)-induced acute lung injury (sTBI-ALI) is regarded as the most common complication of sTBI that is an independent predictor of poor outcomes in patients with sTBI and strongly increases sTBI mortality. Polydatin (PD) has been shown to have a potential therapeutic effect on sTBI-induced neurons injury and sepsis-induced acute lung injury (ALI), therefore, it is reasonable to believe that PD has a protective effect on sTBI-ALI. Here, to clarify the PD protective effect following sTBI-ALI, a rat brain injury model of lateral fluid percussion was established to mimic sTBI. As a result, sTBI induced ALI, and caused an increasing of wet/dry weight ratio and lung vascular permeability, as well as sTBI promoted oxidative stress response in the lung; sTBI caused inflammatory cytokines release, such as IL-6, IL-1β, TNF-α and MCP-1; and sTBI promoted NETs formation, mainly including an increasing expression of MPO, NE and CitH3. Simultaneously, sTBI induced a significant increase in the level of S100B; however, when inhibition of S100B, the expression of MPO, NE and CITH3 were significantly inhibited following sTBI. Inhibition of S100B also promoted lung vascular permeability recovery and alleviated oxidative stress response. Furthermore, PD treatmentreduced the pathological lung damage, promoted lung vascular permeability recovery, alleviated oxidative stress response and inflammatory cytokines release; more importantly, PD inhibited the expression of S100B, and NETs formation in the lung following sTBI. These results indicate that PD alleviates sTBI-ALI by inhibiting S100B mediated NETs formation. Thus, PD may be valuable in sTBI-ALI treatment.

Topics: Acute Lung Injury; Animals; Brain Injuries, Traumatic; Disease Models, Animal; Extracellular Traps; Glucosides; Humans; Lung; Male; Oxidative Stress; Rats; S100 Calcium Binding Protein beta Subunit; Stilbenes

The protecting effects of 3,5,4'-tri-O-acetylresveratrol (AC-Res) on seawater inhalation-induced acute respiratory distress syndrome (ARDS) by interfering with the activation of thioredoxin-1 (Trx-1) pathway were evaluated. Seawater inhalation-induced ARDS was assessed by magnitude of pulmonary edema and lung inflammation. Oxidative stress was tested by T-SOD activity and MDA content in lungs and cells. Besides, Trx-1, nuclear factor erythroid 2-related factor 2 (Nrf2) and Txnip expression were measured to explore how seawater induced oxidative stress and the mechanism by which AC-Res attenuated seawater inhalation-induced ARDS. The results showed that seawater inhalation increased wet-to-dry (W/D) ratios of lung tissues, enhanced secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and disturbed the oxidative distress balance probably through interfering the activity of Trx-1 pathway. While treatment of AC-Res in vivo and Res in vitro reduced W/D ratios of lung tissues, decreased cytokines in lungs and maintained the oxidative stress balance through Trx-1 pathway. In conclusion, AC-Res treatment attenuated seawater inhalation induced ARDS via Trx-1 pathway.

Topics: Acetates; Acute Lung Injury; Administration, Inhalation; Animals; Interleukin-1beta; Lung; Oxidative Stress; Seawater; Stilbenes; Thioredoxins; Tumor Necrosis Factor-alpha

BACKGROUND Resveratrol (Res) is a type of polyphenol found in many plants, which can protect important organs from the damage induced by sepsis. However, the exact mechanism of its protective effect has not been established. This study investigated the effect of Res on the PI3K/Nrf2/HO-1 signaling pathway in rats with sepsis-induced acute lung injury (ALI). MATERIAL AND METHODS Male Wistar rats were treated with 30 mg/kg Res by intraperitoneal administration for 1 hour immediately after cecal ligation and puncture. Levels of MIP-2, IL-18, and IL-10 in bronchoalveolar lavage fluid (BALF) were determined. Lung tissues were collected to measure the wet-to-dry (W/D) ratios, oxidative stress index, and lung injury scores. Expression levels of Akt, p-Akt, HO-1, Nrf-2, and active caspase-3 proteins were determined by western blotting; expression of HO-1 mRNA was determined by RT-PCR. RESULTS Treatment with Res significantly decreased the levels of MIP-2 and IL-18 and increased IL-10 in the BALF of rats with sepsis-induced ALI. In addition, Res also effectively reduced the W/D lung weight ratio, lung injury score, and the levels of MDA (malondialdehyde) and 8-OHdG. Conversely, Res increased SOD (superoxide dismutase) activity in the lung tissue. Moreover, Res significantly induced higher HO-1 mRNA expression, upregulated HO-1 and Nrf-2 protein expression, and the phosphorylation of Akt in the lung tissue. In contrast, the levels of activated caspase-3 protein were decreased in Res-treated rats (P<0.05). CONCLUSIONS Res could inhibit inflammation, oxidative stress, and cell apoptosis to alleviate ALI in septic rats through the inhibition of the PI3K/Nrf2/HO-1 signaling pathway.

Topics: Acute Lung Injury; Animals; Apoptosis; Bronchoalveolar Lavage Fluid; Chemokine CXCL2; Heme Oxygenase-1; Interleukin-10; Interleukin-18; Male; NF-E2-Related Factor 2; Oxidative Stress; Phosphatidylinositol 3-Kinase; Random Allocation; Rats; Rats, Wistar; Resveratrol; Sepsis; Signal Transduction; Stilbenes

Heme oxygenase-1 (HO-1) can exert anti-inflammatory and antioxidant effects. Acute lung injury (ALI) is associated with increased inflammation and influx of proinflammatory cells and mediators in the airspaces and lung parenchyma. In this study, we demonstrate that pterostilbene 4'-

Topics: Acute Lung Injury; Animals; Antioxidants; Disease Models, Animal; Enzyme Induction; Epithelial Cells; Glucosides; Heme Oxygenase-1; Humans; Inflammation; Lipopolysaccharides; Lung; Macrophages; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pseudomonas aeruginosa; RAW 264.7 Cells; RNA, Messenger; Stilbenes; Up-Regulation

Radiation-induced lung injury (RILI) is one of the most common and fatal complications of thoracic radiotherapy. It is characterized with two main features including early radiation pneumonitis and fibrosis in later phase. This study was to investigate the potential radioprotective effects of polydatin (PD), which was shown to exert anti-inflammation and anti-oxidative capacities in other diseases. In this study, we demonstrated that PD-mitigated acute inflammation and late fibrosis caused by irradiation. PD treatment inhibited TGF-β1-Smad3 signalling pathway and epithelial-mesenchymal transition. Moreover, radiation-induced imbalance of Th1/Th2 was also alleviated by PD treatment. Besides its free radical scavenging capacity, PD induced a huge increase of Sirt3 in culture cells and lung tissues. The level of Nrf2 and PGC1α in lung tissues was also elevated. In conclusion, our data showed that PD attenuated radiation-induced lung injury through inhibiting epithelial-mesenchymal transition and increased the expression of Sirt3, suggesting PD as a novel potential radioprotector for RILI.

Topics: Acute Lung Injury; Animals; Cell Line; Disease Models, Animal; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Gene Expression Regulation; Glucosides; Humans; Lung; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Radiation Pneumonitis; Radiation-Protective Agents; Signal Transduction; Sirtuin 3; Smad3 Protein; Stilbenes; Th1-Th2 Balance; Transforming Growth Factor beta1

The present study focused on the therapeutic effects of resveratrol in a rat model of blunt chest trauma-induced acute lung injury and the potential role of endocan as a biomarker of inflammation. They were randomly divided into the following four groups (n = 7 in each group): control group (no treatment or trauma); trauma group (trauma-induced group); resveratrol group (resveratrol [0.3 mg/kg] administered via the i.p. route group); and resveratrol + trauma group (resveratrol [0.3 mg/kg] administered via the i.p. route 1 h prior to the induction of trauma At the end of the 24 h, all the experimental rats were sacrificed. Lung lobe and blood samples were collected for biochemical, histopathological, and immunohistochemical investigations. Serum endocan levels were found to be significantly higher in the travma, resveratrol, and resveratrol + trauma groups than in the control group (p < 0.001, p < 0.001, p < 0.001). Moreover, in resveratrol + trauma group, endocan showed a significant increase compared to trauma and resveratrol group (p < 0.001, p < 0.001). Serum MDA level was significantly higher in the trauma group than in the control group (p = 0.017). SOD showed a significant increase in resveratrol and resveratrol + trauma groups compared to control group (p < 0.001, p < 0.001). The present study suggested that resveratrol exerted antioxidant properties in a rat model of lung injury after blunt chest trauma. Thus, it may have therapeutic potential in cases of blunt chest trauma-induced lung injury. Serum levels of endocan were not correlated with the inflammation response. The clinical use of endocan as a biomarker of inflammation in lung injury caused by blunt chest trauma is not recommended.

Topics: Acute Lung Injury; Animals; Antioxidants; Biomarkers; Inflammation; Proteoglycans; Rats; Resveratrol; Stilbenes; Thoracic Injuries; Wounds, Nonpenetrating

Intestinal ischemia/reperfusion (IIR) leads to acute lung injury (ALI) distally by aggravating pulmonary oxidative stress. Resveratrol is effective in attenuating ALI through its antioxidant capacity. This study aimed to determine the effects of resveratrol on IIR-induced ALI and to explore the role of mast cells (MCs) activation in a rat model of IIR.. Adult Sprague-Dawley rats were subjected to IIR by occluding the superior mesenteric artery for 60min followed by 4-hour reperfusion. Resveratrol was intraperitoneally injected at a dose of 15mg/kg for 5days before IIR. MCs stabilizer/inhibitor cromolyn sodium and degranulator compound 48/80 were used to explore the interaction between resveratrol and MCs. Lung tissues were collected for pathological detection and MCs staining. Pulmonary protein expression of surfactant protein-C (SP-C), tryptase, p47. At the end of IIR, lung injury was significantly increased and was associated with decreased expression of SP-C and increased lung oxidative stress. Increased inflammation as well as activation of MCs was also observed in the lungs after IIR. All these changes were prevented or reversed by resveratrol pretreatment or MCs inhibition with cromolyn sodium. However, these protective effects of resveratrol or cromolyn sodium were reduced by MCs degranulator compound 48/80.. These findings reveal that resveratrol attenuates IIR-induced ALI by reducing NADPH oxidase protein expression and inflammation through stabilizing MCs.

Topics: Acute Lung Injury; Animals; Antioxidants; Disease Models, Animal; Intestinal Diseases; Male; Mast Cells; NADPH Oxidases; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Resveratrol; Stilbenes

Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. Resveratrol and curcumin are proven to have potent anti-inflammatory efficacy, but their clinical application is limited by their metabolic instability. Here, a series of resveratrol and the Mono-carbonyl analogs of curcumin (MCAs) hybrids were designed and synthesized by efficient aldol construction strategy, and then screened for anti-inflammatory activities in vitro and in vivo. The results showed that the majority of analogs effectively inhibited the LPS-induced production of IL-6 and TNF-α. Five analogs, a9, a18, a19, a20 and a24 exhibited excellent anti-inflammatory activity in a dose-dependent manner along with low toxicity in vitro. Structure activity relationship study revealed that the electron-withdrawing groups at meta-position and methoxyl group (OCH

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Curcumin; Gene Expression Regulation; Humans; Interleukin-6; Lung; Mice; RAW 264.7 Cells; Resveratrol; RNA, Messenger; Stilbenes; Tumor Necrosis Factor-alpha

Drowning is a cause of accidental mortality. However, survival may result in acute lung injury. The aim of the present study was to evaluate the effects of 3,5,4'-tri-O-acetylresveratrol (AC-Res) on acute lung injury (ALI) induced by seawater inhalation in rats. ALI models were established by the tracheal instillation of artificial seawater with or without 50 mg/kg AC-Res pretreatment for 7 days. Lung samples from different groups were harvested 4 h after the model was established. Histological changes, blood vessel permeability, inflammatory factor secretion and expression states of the nuclear factor-κB (NF-κB) and inducible NOS (i-NOS) pathway were assessed to evaluate seawater‑induced lung injury and the protective effects of acetylated resveratrol. The results showed that seawater inspiration led to physiological structure changes and an increased permeability of blood vessels. In addition, seawater stimulation enhanced the expression levels of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-1 β (IL-1β) secretion in vitro and in vivo. Notably, seawater inhalation increased NF-κB and i-NOS expression in lungs and cells. On the other hand, pretreatment of AC-Res inhibited the abnormal expression of the NF-κB and i-NOS pathways, followed by decreased NO, TNF-α and IL-1β secretion, protein and cell content in bronchoalveolar lavage fluid (BALF) and Evans blue, protein and cell infiltration from blood vessels into lung tissues. The results therefore suggest that AC-Res attenuated seawater inhalation induced‑ALI by interfering with the NF-κB and i-NOS pathways.

Topics: Acetylation; Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Interleukin-1beta; Lung; Male; NF-kappa B; Nitric Oxide Synthase Type II; Rats, Sprague-Dawley; Resveratrol; Seawater; Signal Transduction; Stilbenes

To investigate the effect of resveratrol (Res) on paraquat (PQ)-induced acute lung injury (ALI) and mortality in mice and the mechanism of nuclear factor-ΚB (NF-ΚB) inflammatory pathway.. Sixty-eight healthy male ICR mice with grade SPF were enrolled, among them 20 mice were used for mortality observation (n = 10), and other 48 were used for determination of related parameters (n = 6). The mice were randomly divided into four groups: normal saline (NS) control group, Res control group, PQ group and PQ + Res group. The mice in the latter two groups were subdivided into 6, 24, 72 hours subgroups. The PQ poisoning model of mice was reproduced by one injection of 30 mg/kg PQ intraperitoneally. The mice in PQ + Res group were given 60 mg/kg Res intraperitoneally on the contralateral side after PQ injection. The mice were sacrificed at 6, 24, 72 hours after PQ poisoning, and lung tissue was harvested. The serum levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-1β) were determined by enzyme linked immunosorbent assay (ELISA). The pathological changes in lung tissue were observed with electron microscopy. Apoptosis cells in the lung were identified by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) for the estimation of apoptosis rate. The protein expression of NF-ΚB p65 was determined by Western Blot.. Compared with PQ group, the death number of mice at 48, 72, 96 hours in PQ + Res group was slightly decreased (0 vs. 2, 2 vs. 5, 4 vs. 6) but without statistically significant difference (all P > 0.05). Under electron microscope, the lung injury in PQ group was severer than that in NS control group, and Res was found to be able to alleviate the lung injury. Compared with NS control group [(2.45±0.61)%], the apoptosis rate at 6 hours in PQ group was significantly increased [(8.42±1.48)%], and peaked at 72 hours [(21.23±3.47)%]. Res could decrease the apoptosis rate after PQ poisoning [6 hours: (5.56±1.31)% vs. (8.42±1.48)%, 24 hours: (11.14±2.07)% vs. (16.88±2.96)%, 72 hours: (13.28±2.32)% vs. (21.23±3.47)%, all P < 0.05]. The serum levels of TNF-α, IL-6, and IL-1β, and NF-ΚB p65 in lung tissue were all markedly increased after PQ poisoning, and they were significantly decreased after Res intervention as compared with those of PQ group [TNF-α (ng/L): 2.62±0.29 vs. 4.06±0.74 at 6 hours, 3.98±0.41 vs. 6.79±0.80 at 24 hours, 5.06±0.75 vs. 11.00±0.75 at 72 hours; IL-6 (ng/L): 14.19±1.54 vs. 16.55±1.24 at 6 hours, 13.21±1.37 vs. 19.73±0.85 at 24 hours, 13.72±0.56 vs. 22.45±0.72 at 72 hours; IL-1β (ng/L): 8.54±1.64 vs. 12.59±0.66 at 6 hours, 10.15±0.29 vs. 16.24±1.03 at 24 hours, 16.14±0.70 vs. 19.55±0.56 at 72 hours; 6-hour NF-ΚB p65: (1.34±0.07) folds vs. (1.86±0.11) folds when the expression in NS control group was represented as 1, all P < 0.05].. Res cannot lower the mortality in mice with PQ poisoning, but it seems to be able to attenuate PQ-induced ALI and cell apoptosis. The mechanism responsible for the latter maybe the inhibitive effect of Res on NF-ΚB p65 translocation and cytokines production.

Topics: Acute Lung Injury; Animals; Apoptosis; Interleukin-1beta; Interleukin-6; Lung; Male; Mice; Mice, Inbred ICR; NF-kappa B; Paraquat; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1β and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI. Resveratrol treatment alleviated the LPS-induced lung pathological damage, lung edema and neutrophil infiltration. In addition, resveratrol reversed the LPS-mediated elevation of IL-1β and IL-18 level in the BAL fluids. In lung tissue, resveratrol also inhibited the LPS-induced NLRP3, ASC, caspase-1 mRNA and protein expression, and NLRP3 inflammasome activation. Moreover, resveratrol administration not only suppressed the NF-κB p65 nuclear translocation, NF-κB activity and ROS production in the LPS-treated mice, but also inhibited the LPS-induced thioredoxin-interacting protein (TXNIP) protein expression and interaction of TXNIP-NLRP3 in lung tissue. Meanwhile, resveratrol obviously induced SIRT1 mRNA and protein expression in the LPS-challenged mice. Taken together, our study suggests that resveratrol protects against LPS-induced lung injury by NLRP3 inflammasome inhibition. These findings further suggest that resveratrol may be of great value in the treatment of ALI and a potential and an effective pharmacological agent for inflammasome-relevant diseases.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Inflammasomes; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Random Allocation; Resveratrol; Stilbenes

Neutrophils are the first cells to achieve the sites of infection or inflammation in the lungs. The massive accumulation of these cells is associated with acute and chronic lung injury. Therefore, they have been implicated in the pathogenesis of many lung diseases through the release of reactive oxygen intermediates, proteolytic enzymes and Neutrophil Extracellular Traps (NETs). The excessive and continuous release of NETs, fibers composed by decondensed chromatin coated with neutrophil proteins, are associated to the impairment of lung function in different pathological settings. Flavonoids inhibit the respiratory burst of neutrophils in mammals. However, one of these flavonoids, resveratrol has a particular chemical property. It reduce Cu(II) to Cu(I) form with concomitant formation of reactive oxygen species, which can produce DNA breakage as reported in several in vitro models. We hypothesize that direct resveratrol administration in lungs can cleave DNA in NETs, improving lung function during acute airway infections or chronic inflammatory lung diseases. If the hypothesis is correct, the control of NET formation can be used to reduce the inflammatory environment in lung after neutrophil stimuli. Additionally, the production of proinflammatory cytokines by neutrophils could be also diminished by resveratrol administration. In this sense, this flavonoid provides a multifaceted opportunity for treatment of lung diseases with strong or chronic neutrophil activation.

Topics: Acute Lung Injury; Antioxidants; Chromatin; DNA Damage; Flavonoids; Humans; Inflammation; Lung; Models, Theoretical; Neutrophils; Reactive Oxygen Species; Respiratory Function Tests; Resveratrol; Stilbenes

Silent information regulator type-1 (SIRT1) has been reported to be involved in the cardiopulmonary protection. However, its role in the pathogenesis of burn-induced remote acute lung injury (ALI) is currently unknown. The present study aims to investigate the role of SIRT1 in burn-induced remote ALI and the involved signaling pathway. We observed that SIRT1 expression in rat lung tissue after burn injury appeared an increasing trend after a short period of suppression. The upregulation of SIRT1 stimulated by resveratrol exhibited remission of histopathologic changes, reduction of cell apoptosis, and downregulation of pro-inflammatory cytokines in rat pulmonary tissues suffering from severe burn. We next used primary pulmonary microvascular endothelial cells (PMVECs) challenged by burn serum (BS) to simulate in vivo rat lung tissue after burn injury, and found that BS significantly suppressed SIRT1 expression, increased cell apoptosis, and activated p38 MAPK signaling. The use of resveratrol reversed these effects, while knockdown of SIRT1 by shRNA further augmented BS-induced increase of cell apoptosis and activation of p38 MAPK. Taken together, these results indicate that SIRT1 might protect lung tissue against burn-induced remote ALI by attenuating PMVEC apoptosis via p38 MAPK signaling, suggesting its potential therapeutic effects on the treatment of ALI.

Topics: Acute Lung Injury; Animals; Apoptosis; Burns; Caspase 3; Cells, Cultured; Cytokines; Disease Models, Animal; Endothelial Cells; Lung; Male; MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases; Permeability; Rats; Rats, Sprague-Dawley; Resveratrol; RNA Interference; RNA, Messenger; RNA, Small Interfering; Sirtuin 1; Stilbenes

Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol-chalcone compounds (5a-5m, 6a-6i) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-α expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol-chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Aza Compounds; Cell Line; Chalcones; Humans; Interleukin-6; Lipopolysaccharides; Lung; Macrophages; Mice; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

The purpose of this study was to investigate the protective effect of PD against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its potential mechanism. In vivo, PD and dexamethasone were intraperitoneally administered 1h before LPS stimulation. Then, mice were sacrificed at 6h post-LPS stimulation. Neutrophil number, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were determined, as well as lung wet to dry ratio (W/D) and polymorphonuclear (MPO) activity. The protein expressions of Toll like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), IL-1R-associated kinases 1 (IRAK1), IRAK4, inhibitor of nuclear factor kappa-B kinase (IKK)α, p-IKKα, IKKβ, p-IKKβ, inhibitor of NF-κB (IκBα), p-IκBα and NF-κB in lung tissues were assessed. Besides, we detected the IL-6, IL-1β, IL-8, TNF-α levels and TLR4, MyD88, NF-κB protein expressions in LPS-induced BEAS-2B cells. Consequently, PD significantly inhibited the levels of W/D, MPO, neutrophils number, TNF-α, IL-6, IL-1β and reversed TLR4-MyD88-NF-κB signaling pathway in lung tissues. In vitro assays, PD effectively negatively mediated the inflammatory cytokines and ameliorated the high expressions of TLR4, MyD88, NF-κB caused by LPS simulation in Human bronchial epithelial BEAS-2B cells. This study indicated that PD played a protective role in LPS-induced ALI and BEAS-2B cells. The results supported further study of PD as potential candidate for acute lung injury.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Cell Line; Cytokines; Glucosides; Leukocyte Count; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Myeloid Differentiation Factor 88; NF-kappa B; Signal Transduction; Stilbenes; Toll-Like Receptor 4

Resveratrol, a natural plant polyphenol, has received increasing attention because its varied bioactivities, including the inhibition of tumorigenesis, lipid modification and calorie-restriction. We aimed to investigate the effect of resveratrol on oxidative/nitrative stress in endotoxemia-associated acute lung injury.. Mice were injected with lipopolysaccharide (LPS, 5 mg/kg, ip). Resveratrol at a dose of 0.3 mg/kg was administered alone or immediately before injection of LPS. Twenty four hours later, lung tissues were collected for histopathologic examination, and determination of malondialdehyde (MDA), H2O2, reduced/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) and peroxynitrite production.. Resveratrol treatment improves histopathological changes in the lung during endotoxemia. Increased oxidative stress in endotoxemic lung was reversed by resveratrol treatment, as evidenced by the decreases of pro-oxidant biomarker (MDA and H2O2), and the increases of anti-oxidant biomarkers (GSH/GSSG ratio, T-AOC, CAT and SOD activity). Treatment with resveratrol inhibited endotoxemia-induced iNOS expression and NO production. Moreover, peroxynitrite formation in endotoxemic lung was significantly attenuated after resveratrol treatment.. Resveratrol exerts protective effects against acute endotoxemia-associated lung injury. These beneficial effects may be due to both the anti-oxidant and anti-nitrative properties of resveratrol. These findings support the potential for resveratrol as a possible pharmacological agent to reduce acute lung injury resulting from oxidative/nitrative damage.

Topics: Acute Lung Injury; Animals; Antioxidants; Disease Models, Animal; Endotoxemia; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidative Stress; Peroxynitrous Acid; Resveratrol; Stilbenes; Superoxide Dismutase

Heme oxygenase-1 (HO-1) is an important anti-inflammatory, antioxidative and cytoprotective enzyme that is regulated by the activation of the major transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In the present study, six stilbene derivatives isolated from Rheum undulatum L. were assessed for their antioxidative potential. In the tert-butylhydroperoxide (t-BHP)-induced RAW 264.7 macrophage cell line, desoxyrhapontigenin was the most potent component that reduced intracellular reactive oxygen species (ROS) and peroxynitrite. In response to desoxyrhapontigenin, the mRNA expression levels of antioxidant enzymes were up-regulated. An electrophoretic mobility shift assay (EMSA) confirmed that desoxyrhapontigenin promoted the DNA binding of Nrf2 and increased the expression of antioxidant proteins and enzymes regulated by Nrf2. Further investigation utilizing specific inhibitors of Akt, p38, JNK and ERK demonstrated that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediates HO-1 expression. Moreover, the increase in Nrf2 expression mediated by treatment with desoxyrhapontigenin was reversed by Nrf2 or Akt gene knock-down. In the LPS-induced in vivo lung inflammation model, pretreatment with desoxyrhapontigenin markedly ameliorated LPS-induced lung inflammation and histological changes. Immunohistochemical analysis of Nrf2, HO-1 and p65 was conducted and confirmed that treatment with desoxyrhapontigenin induced Nrf2 and HO-1 expression but reduced p65 expression. These findings suggest that desoxyrhapontigenin may be a potential therapeutic candidate as an antioxidant or an anti-inflammatory agent.

Topics: Acute Lung Injury; Animals; Disease Models, Animal; Gene Expression Regulation; Heme Oxygenase-1; Lipopolysaccharides; Macrophages, Alveolar; Male; MAP Kinase Signaling System; Membrane Proteins; Mice; Mice, Inbred ICR; NF-E2-Related Factor 2; Peroxynitrous Acid; Plant Extracts; Reactive Oxygen Species; Rheum; Stilbenes

Resveratrol, a polyphenol mainly present in grapes and red wine, demonstrated varied pharmacological activities. The protective effects of resveratrol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) have remained elusive. The present study investigated whether the protective effect of resveratrol on ALI induced by LPS was via inhibiting the myeloid differentiation primary response gene (myd88)‑dependent toll‑like receptor (TLR)4 signaling pathway. Mice were pretreated with 5 or 45 mg/kg resveratrol for three days prior to bronchial perfusion with 25 mg/kg LPS. At 12 h after surgery, the ratio of the wet to the dry (w/d) lung was calculated to assess tissue edema. Histological changes of the lungs were detected using hematoxylin and eosin staining and the protein expression levels of TLR4, myd88 and nuclear factor kappa‑light‑chain‑enhancer of activated B cells (NF‑κB) were measured by western blot analysis. The concentration of interleukin (IL)‑6 and cyclooxygenase (COX)‑2 in the bronchoalveolar lavage fluid were detected by ELISA. The results showed that resveratrol can suppress the edema, inflammatory cell infiltration and alveolar structure damage of lungs in mice with ALI and decrease the lung w/d ratio. Additionally, resveratrol markedly decreased the expression of TLR4, myd88 and NF‑κB and decreased the concentration of inflammatory cytokines, including IL‑6 and COX‑2. Therefore, it can be concluded that resveratrol has a protective effect against ALI induced by LPS, at least in part by inhibiting the myd88‑dependent TLR4 signaling pathway. In conclusion, resveratrol pretreatment has a protective effect against LPS‑induced ALI in mice, which indicates that resveratrol may serve as a potential therapeutic agent for treating ALI in the clinic.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchoalveolar Lavage Fluid; Cyclooxygenase 2; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Interleukin-6; Leukocytes; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Myeloid Differentiation Factor 88; NF-kappa B; Resveratrol; Signal Transduction; Stilbenes; Toll-Like Receptor 4

Polydatin (PD) has anti-inflammatory and anti-apoptotic effects in ischemic-reperfusion injury. Moreover, inflammatory responses and apoptosis play a role in the development of burn-induced lung injuries. Based on these findings, in this study we investigated the hypothesis that PD can ameliorate lung injury induced by extensive burns via reduction of inflammation and apoptosis.. Rats were subjected to 30% total body surface area burn injury followed by resuscitation. The treatment group received 45 mg/kg PD, and the burn group received the same amount of normal saline solution. No burn injury was inflicted in the sham group. Microvascular permeability, interstitial edema, neutrophil recruitment, and histopathological changes were detected by measuring Evans blue concentration, wet-to-dry lung weight ratio (W/D), myeloperoxidase (MPO) activity, and hematoxylin and eosin staining, respectively. To investigate the mechanism of action of PD, enzyme-linked immunosorbent assay, cell counting, terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-triphosphate-digoxigenin nick end labeling (TUNEL) staining, fluorometric assay, and Western blot were used for assessing levels of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]-1β, and IL-6), total number of cells, and concentration of polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage fluid (BALF), the number of apoptotic cells, caspase-3 activity, and apoptosis-related proteins including Bax and Bcl-xl, respectively.. Burn-injury rats exhibited significant lung injury characterized by the deterioration of histopathological characteristics, pulmonary microvascular hyperpermeability, and a high W/D, which were attenuated by PD (P = .007 for permeability, P = .004 for W/D). PD inhibited the burn-induced inflammatory response, as evidenced by the down-regulation of lung MPO activity (P = .008), total number of cells, PMN concentration in BALF, and the local and systemic levels of the pro-inflammatory cytokines examined. Moreover, PD treatment dramatically prevented burn-induced pulmonary cell apoptosis in lungs, as reflected by the decrease in the number of TUNEL-positive cells (P = .002) and changes in Bax, Bcl-xl, and caspase-3 activity (P = .03).. PD ameliorates burn-induced lung injury via its anti-inflammatory and anti-apoptotic effects, and PD treatment may therefore serve as a potential therapeutic target for the treatment of critical burn injuries.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Bronchoalveolar Lavage Fluid; Burns; Capillary Permeability; Caspase 3; Down-Regulation; Glucosides; Interleukin-1beta; Interleukin-6; Leukocyte Count; Lung; Male; Neutrophils; Organ Size; Peroxidase; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Stilbenes; Survival Rate; Tumor Necrosis Factor-alpha

High-mobility group protein box 1 (HMGB1) is essential in the response to injury during sepsis. We hypothesized that resveratrol (RESV) administration would inhibit nuclear-cytoplasmic HMGB1 translocation in hepatocytes, which is associated with sirtuin 1 (SIRT1) upregulation. We investigated the regulatory role of SIRT1 in HMGB1 nucleocytoplasmic translocation and its effect on sepsis-induced liver injury.. Rats were randomly assigned to pretreatment with RESV (60 mg/kg per day), nicotinamide (60 mg/kg per day), or vehicle (olive oil), which was administered by gavage for 3 days directly before cecal ligation and puncture was performed to induce sepsis. Parallel control groups were established. Rats were killed 24 h after surgery, and cytokine production, histology, apoptosis, SIRT1, serum HMGB1, nuclear and cytoplasmic HMGB1/ac-HMGB1, and the interaction between SIRT1 and HMGB1 were evaluated. In vitro evaluations were performed in human liver L02 cells subjected to lipopolysaccharide-induced injury, and siRNA-mediated SIRT1 knockdown experiments were performed.. Sepsis-induced serum aminotransferase activities and proinflammatory chemokine levels were reduced by RESV pretreatment, which also improved liver histological parameters in association with SIRT1 upregulation. Resveratrol inhibited HMGB1 cytoplasmic translocation. Nicotinamide, an SIRT1 inhibitor, reduced the SIRT1-mediated suppression of HMGB1 translocation and aggravated cecal ligation and puncture-induced liver damage. Sirtuin 1 knockdown in vitro confirmed that RESV increased the SIRT1-mediated repression of HMGB1 translocation. In vivo, SIRT1 and HMGB1 physically interacted in the nucleus, and SIRT1 regulated HMGB1 acetylation in response to septic liver injury.. Resveratrol protects against sepsis-induced liver injury through the SIRT1-mediated HMGB1 nucleocytoplasmic translocation pathway, a new potential therapeutic target in sepsis-induced liver injury.

Topics: Acetylation; Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Cell Nucleus; Cells, Cultured; Cytoplasm; Drug Evaluation, Preclinical; Gene Knockdown Techniques; Hepatocytes; HMGB1 Protein; Male; Molecular Targeted Therapy; Oxidative Stress; Rats, Sprague-Dawley; Resveratrol; Sepsis; Sirtuin 1; Stilbenes; Translocation, Genetic; Up-Regulation

Anti-inflammatory and anti-apoptotic effects of polydatin (PD) have been demonstrated in our previous studies. Recently, we have found that PD treatment can ameliorate burn-induced acute lung injury (ALI). In the present study, we hypothesized that PD may provide protective effect against LPS-induced ALI through reducing inflammation and apoptosis. Rats were respectively pretreated with PD at doses of 15, 30 and 45 mg/kg weight, followed by intratracheal administration of lipopolysaccharide (LPS). LPS-challenged rats exhibited significant lung injury characterized by the deterioration of histopathology, pulmonary microvascular hyperpermeability, wet-to-dry weight ratio, and oxygenation index, which was attenuated by PD (30 and 45 mg/kg) treatment. Moreover, PD (30 and 45 mg/kg) treatment inhibited LPS-induced inflammatory response, as evidenced by the downregulation of lung myeloperoxidase activity, total cells and PMNs in bronchoalveolar lavage fluid, and the systemic levels of the pro-inflammatory cytokines. Furthermore, PD (30 and 45 mg/kg) treatment remarkably improved LPS-induced increase in TUNEL (deoxynucleotidyl transferase dUTP nick end labeling) staining-positive cells, caspase 3 activity, Bax over-expression and Bcl-2 down-expression. In conclusion, these results demonstrate that PD (30 and 45 mg/kg) treatment attenuates LPS-induced ALI through reducing lung inflammation and apoptosis.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Apoptosis; Blotting, Western; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Glucosides; In Situ Nick-End Labeling; Inflammation; Lipopolysaccharides; Male; Rats; Rats, Sprague-Dawley; Stilbenes

The aim of the present study was to examine the effects of 3,5,4'-tri-O-acetylresveratrol on connexin 43 (Cx43) in acute lung injury (ALI) in rats induced by tracheal instillation of artificial seawater. Different doses (50, 150, and 450 mg/kg) of 3,5,4'-tri-O-acetylresveratrol were administered orally for 7 days before modeling. Four hours after seawater inhalation, histological changes, contents of TNF- α , IL-1 β and IL-10, and the expression of Cx43 in lungs were detected. Besides, the gap junction communication in A549 cells and human umbilical vein endothelial cells (HUVECs) challenged by seawater was also evaluated. Histological changes, increased contents of inflammatory factors, upregulation in gene level, and deregulation in protein level of Cx43 in lungs stimulated by seawater were observed. On the other hand, pretreatment with 3,5,4'-tri-O-acetylresveratrol significantly inhibited infiltration of inflammation, development of pulmonary edema, and contents of inflammatory mediators in lungs. Above all, 3,5,4'-tri-O-acetylresveratrol upregulated the expression of Cx43 in both gene and protein levels, and its intermediate metabolite, resveratrol, also enhanced the gap junction communication in the two cell lines. The results of the present study suggested that administration of 3,5,4'-tri-O-acetylresveratrol may be beneficial for treatment of inflammatorycellsin lung.

Topics: Acute Lung Injury; Animals; Blotting, Western; Cell Line; Connexin 43; Humans; Interleukin-10; Interleukin-1beta; Lung; Male; Rats; Rats, Sprague-Dawley; Resveratrol; Seawater; Stilbenes; Tumor Necrosis Factor-alpha

The development of acute lung injury (ALI) during sepsis almost doubles the mortality rate of patients. The efficacy of current treatment strategies is low as treatment is usually initiated following the onset of symptoms. Inflammation is one of the main mechanisms of autoimmune disorders and is a common feature of sepsis. The suppression of inflammation is therefore an important mechanism for the treatment of sepsis. Sirtuin 1 (Sirt1) has been demonstrated to play a role in the regulation of inflammation. Resveratrol, a potent Sirt1 activator, exhibits anti‑inflammatory properties. However, the role of resveratrol for the treatment of ALI during sepsis is not fully understood. In the present study, the anti‑inflammatory role of Sirt1 in the lipopolysaccharide (LPS)‑induced TC‑1 cell line and its therapeutic role in ALI was investigated in a mouse model of sepsis. The upregulation of matrix metalloproteinase-9, interleukin (IL)‑1β, IL‑6 and inducible nitric oxide synthase was induced by LPS in the mouse model of sepsis and the TC‑1 cell line, and resveratrol suppressed the overexpression of these proinflammatory molecules in a dose‑dependent manner. Resveratrol decreased pulmonary edema in the mouse model of sepsis induced by LPS. In addition, resveratrol improved lung function and reduced pathological alterations in the mouse model of sepsis. Knockdown of Sirt1 by RNA interference resulted in an increased susceptibility of TC‑1 cells to LPS stimulation and diminished the anti‑inflammatory effect of resveratrol. These results demonstrated that resveratrol inhibits LPS‑induced ALI and inflammation via Sirt1, and indicated that Sirt1 is an efficient target for the regulation of LPS‑induced ALI and inflammation. The present study provides insights into the treatment of ALI during sepsis.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Disease Models, Animal; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Male; Matrix Metalloproteinase 9; Mice; Nitric Oxide Synthase Type II; Resveratrol; RNA Interference; RNA, Small Interfering; Sepsis; Sirtuin 1; Stilbenes; Up-Regulation

Resveratrol, a phytoalexin found in a range of plant products, may exert a variety of pharmacological activities. In this study, we investigated the effect of resveratrol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo, and we found that the pretreatment with resveratrol can effectively protect mice against LPS-induced ALI. Mice were pretreated with 1 mg/kg resveratrol for 3 days before challenging with a dose of 15 mg/kg LPS. The histological result showed that resveratrol can suppress the edema, inflammatory cell infiltration, and alveolar structure damage of lungs in ALI mice, and a decrease in the lung W/D ratio was also observed in mice with resveratrol pretreatment. Additionally, resveratrol markedly decreased the production of inflammatory cytokines, including IL-1β and MIP-1α and prevented the release of nitric oxide (NO) through inhibiting the expression of inducible NO synthase in lung tissues. Furthermore, the pretreatment with resveratrol suppressed the nuclear translocation of NF-κB in lung tissues, which may be partly responsible for its effect on the ALI. In conclusion, the results presented here may suggest resveratrol as a potential therapeutic agent for treating ALI in the future.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Chemokine CCL3; Disease Models, Animal; Interleukin-1beta; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Nitric Oxide Synthase Type II; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stilbenes

To study the effect of resveratrol to the onset and progress of acute lung injury in rat model of severe acute pancreatitis (SAP).. The SAP model was made by injecting 4% sodium taurocholate, a dosage of 0.1 mL/100 g, into the biliopancreatic duct. The control group is formed by injecting the equal amount of N. S into the biliopancreatic duct. For treatment group, after induction of the SAP model, the resveratrol was used to injection at a dosage of 0.3 mL/100 g through the penis vein; at solvent group, after induction of the SAP model, injecting the same amount of tween 80 through the penis vein. All rats were sacrificed at 3, 6, 12 hours. The injuries of lung were checked by pulmonary morphology change, the change of protein in bronchi alveolar lung fluid (BALF). The changes of iNOS were analyzed with special method. PECAM-1, TGF-beta1 was also detected by immunohistochemistry.. For pulmonary morphology change, there were more inflammation cells, more pulmonary edema in experimental group than in treatment group. And in experimental group, with the postponement, the amount of iNOS is increasing (P < 0.05). However, in treatment group, the amout of iNOS was significantly less than in experimental group. The same case was that PECAM-1 and TGF-beta1 of experimental group were higher expression than that of treatment group (P < 0.05).. Resveratrol can inhibit the expression of iNOS, PECAM-1, TGF-beta1, and reduce the adhesion between inflammatory cells and endothelium cells, so it may reduce the severity of acute lung injury complicated with severe acute pancreatitis.

Topics: Acute Lung Injury; Animals; Bronchoalveolar Lavage Fluid; Disease Progression; Gene Expression Regulation; Lung; Male; Nitric Oxide Synthase Type II; Pancreatitis; Platelet Endothelial Cell Adhesion Molecule-1; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Transforming Growth Factor beta1