Lung MDA Research Articles

Antiinflammatory effects of matrine in LPS-induced acute lung injury in mice

Matrine is one of the main active components of Chinese herb Sophora flavescens Ait (Kushen), which has been demonstrated to be effective in suppressing inflammation. The aim of the present study is to investigate the effect of matrine on LPS-induced lung injury. Lung injury was assessed by histological study and wet to dry weight ratios, as well as cell count and protein content in bronchoalveolar lavage fluid. We also detected MPO activity reflecting neutrophil infiltration and MDA activity examining oxidative stress in lung tissues. Cytokines and ROS production in cells were monitored by ELISA and flow cytometry, respectively. The results showed that high dose of matrine significantly reduced the mortality rate of mice with LPS administration. Treatment with matrine improved LPS-induced lung histopathologic changes, alleviated pulmonary edema and lung vascular leak, inhibited MPO and MDA activity,and reduced the production of inflammatory mediators including TNF-α, IL-6 and HMGB1. In vitro, matrine administration reduced the production of ROS and inflammatory factors, which was possibly associated with inhibition of NF-κB. In conclusion, the current study demonstrated that matrine exhibited a protective effect on LPS-induced acute lung injury by inhibiting of the inflammatory response, which may involve the suppression of ROS and tissue oxidative stress.

Effect of alveolar recruitment maneuvers combined with lung protection mechanical ventilation on lung injury in a rabbit model of acute respiratory distress syndrome

Objective To evaluate the effect of alveolar recruitment maneuvers (ARM) combined with lung protection mechanical ventilation on lung injury in a rabbit model of acute respiratory distress syndrome (ARDS) .Methods Twenty-four rabbits of both sexes weighing 2.5-3.5 kg were randomly divided into 4 groups (n=6 each):normal control group(group Ⅰ);ARDS group(group Ⅱ);ARDS+lung protection mechanical ventilation group (group Ⅲ) and ARDS + lung protection mechanical ventilation + ARM group (group Ⅳ). The animals were anesthetized with iv pentobarbital 20 mg/kg, tracheostomized and mechanically ventilated. Anesthesia was maintained with iv gammahydroxybutyrate infusion 100 mg·kg-1·h-1 and intermittent iv boluses of vecuronium. ARDS was induced with oleic acid 0.1 ml/kg injected iv over 15 min in Ⅱ ,Ⅲ and Ⅳ groups. In Ⅰand Ⅱ groups VT = 12 ml/kg, RR=30 bpm, I∶E=1.0=2.3, PEEP=0, FiO2=1, while in Ⅲ and Ⅳ groups VT=6 ml/kg, RR=30 bpm, I∶E=1.0=2.3, PEEP=airway pressure at lower inflection point+2 cm H2O, FiO2=1.ARM was performed by increasing the airway pressure to 30 cm H2O for 30 s once an hour in group Ⅳ. Arterial blood gas analysis was performed after each ARM. The animals were sacrificed at 1 h after the 3rd ARM. The lungs were removed for microscopic examination and determination of W/D lung weight ratio, TNF-α, IL-10 and MDA contents and MPO activity. TNF-α/IL-10 ratio was calculated. Results ARDS significantly decreased PaO2/FiO2 and increased TNF-α/IL-10 and W/D lung weight ratio, MPO activity and MDA content in the lung tissue. Lung protection mechanical ventilation significantly increased PaO2/FiO2 and decreased TNF-α/IL-10 and W/ D lung weight ratio, MPO activity and MDA content in the lung tissue. Lung protection mechanical ventilation + ARM significantly increased PaO2/FiO2 and decreased TNF-α/IL-10, W/D lung weight ratio, MDA content and MPO activity in group Ⅳ. Conclusion ARM combined with lung protection mechanical ventilation can further attenuate ARDS-induced lung injury by inhibiting inflammatory response. Key words: Respiration, artificial; Atelectasis; Positive-pressure respiration; Respiratory distress syndrome, adult

Asthma Symptoms, Lung Function, and Markers of Oxidative Stress and Inflammation in Children Exposed to Oil Refinery Pollution

Objectives. Little is known about the effects of exposure to petroleum refinery emissions on respiratory health in children. We evaluated lung function and markers of inflammation and oxidative stress in children and adolescents with and without asthma or wheezing symptoms living in a petrochemical polluted area (Sarroch, Sardinia) versus a reference area (Burcei). Methods. Parents of 275/300 6- to 14-year-old children living in Sarroch and parents of 214/323 children living in Burcei answered a questionnaire on respiratory symptoms and risk factors. Measurements of forced expiratory volume after 1 second (FEV1) and of forced expiratory flow rates at 25–75% of vital capacity (FEF25–75) were available in 27 and 23 asthma/wheezing-positive subjects and in 7 and 54 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively; for fractional exhaled nitric oxide (FENO) corresponding figures were 27 and 24 and 8 and 55 in Sarroch and in Burcei, respectively. Malondialdehyde–deoxyguanosine (MDA–dG) adduct levels in nasal mucosa were measured in 12- to 14-year-old adolescents (8 and 14 asthma/wheezing-positive and 20 and 28 asthma/wheezing-negative subjects in Sarroch and in Burcei, respectively). Air pollutants were assessed during 3 weeks, starting 1 week before lung function, FENO, and MDA–dG measurements. Generalized linear models were used to estimate the effect of the area of residence adjusting for confounders. Results. Weekly average concentrations of sulfur dioxide were 6.9–61.6μg/m3 in Sarroch versus 0.3–7.6μg/m3 in the rural area of Burcei; of nitrogen dioxide, 5.2–28.7μg/m3 versus 1.7–5.3μg/m3; and of benzene, 1.8–9.0μg/m3 versus 1.3–1.5μg/m3, respectively. Children living in Sarroch versus children living in the reference area showed an increase in wheezing symptoms {adjusted prevalence ratio=1.70 [90% confidence interval (CI)=1.01; 2.86]}; a decrease in lung function [variation in FEV1=−10.3% (90% CI=−15.0; −6.0%) and in FEF25–75=−12.9% (90% CI=−20.7; −4.3%)]; an increase in bronchial inflammation [variation in FENO=+35% (90% CI=11.7; 80.1%)]; and an increase in MDA–dG adducts of +83% (90% CI=22.9; 174.1%). Conclusions. Data from this small study are consistent with the role of environmental pollutants on lung function and inflammation.

Effects of remifentanil on lipid peroxidation during hemorrhagic shock-induced acute lung injury in rabbits

Objective To investigate the effects of remifentanil on lipid peroxidation druing hemorrhagic shock-induced acute lung injury （ALI） in rabbits. Methods Thirty-two healthy adult rabbits weighing 2.0-2.5 kg were randomly divided into 4 groups （n = 8 each）： sham operation group （group S）; ALI group; low-dose remifentanil group （group LR）; high-dose remifentanil group （group HR）. The left femoral artery was cannulated for blood-letting and blood sampling. The right femoral artery was cannulated for remifentanil administration. The model of hemorrhagic shock was established by modified Wigger＇ s methods. In group S, only cannulation was performed. In group LR and HR, remifentanil was infused intraperitoneally at 0.66 and 1.32 μg·kg-1 ·min-1 15 min before blood-letting respectively, while group ALI received equal volume of normal saline instead. Arterial blood samples were taken at 0, 20,70 and 100 min after blood-letting （T1-4） for blood gas analysis. The animals were then sacrificed and the lungs were immediately removed for histological examination with light microscope and determination of W/D lung weight ratio, MDA content and SOD activity. Results W/D ratio and MDA content were significantly increased, while SOD activity was significantly decreased in group ALI compared with group S （P 〈0.05）. The pH value at T2 and PaO2 at T2-4 in group LR and the pH value and PaCO2 at T2-4 in group HR were significantly higher than those in group ALI （P 〈 0.05）. W/D ratio and MDA content were significantly lower,while SOD activity was significantly higher in group LR and HR than in group ALI, and in group HR than in group LR （P 〈 0.05）. Remifentanil infusion significantly attenuated the pathologic changes in a dose-dependent manner. Conclusion Remifentanil pretreatment can attenuate hemorrhagic shock-induced ALI through inhibiting lipid peroxidation in rabbits. Key words: Piperidines; Respiratory distress syndrome,adult; Shock,hemorrhagic; Lipid peroxidation

Effects of biliverdin on lung injury induced by brain death in rats

Objective To investigate the effects of exogenous biliverdin on lung injury induced by brain death (BD) in rats. Methods Twenty-three adult male Wistar rats in which Fogarty balloon catheter was successfully inserted into cranial cavity were randomly divided into 3 groups: group Ⅰ sham operation (group S,n = 7); group Ⅱ brain death (group BD, n = 8) and group Ⅲ biliverdin + BD (group B, n = 8). The animals were anesthetized, intubated and mechanically ventilated. Femoral artery and vein were cannulated for MAP monitoring and drug and fluid administration. Brain death was induced by injecting slowly normal saline into the balloon in group Ⅱ and Ⅲ. BD was confirmed by dilated and fixed pupils, apnea, transient hypertension and EEG changes. In group Ⅲ biliverdin 35 mg/kg was injected intraperitoneally as soon as BD was confirmed. The animals were mechanically ventilated for another 1.5 h during which MAP was maintained at 80-120 mm Hg by iv norepinephrine infusion. Arterial blood samples were obtained before anesthesia, immediately before and at 5, 30,60, 90 min after intraperitoneal biliverdin for blood gas analysis and determination of plasma bilirubin concentration. PaO2/FiO2 was calculated. The animals were sacrificed at 1.5 h after biliverdin administration. The left lung was removed for detection of MDA content, SOD activity, total antioxidant capacity, cell apoptosis and biliverdin reductase expression in lung tissue. Results Brain death significantly decreased PaO2/FiO2, lung SOD activity and total antioxidant capacity and increased lung MDA content and apoptosis as compared with sham operation group. IP biliverdin significantly attenuated BD-induced lung injury in group B as compared with group BD. The plasma bilirubin concentration and biliverdin reductase expression were significantly higher in group B than group BD. Conclusion Exogenous biliverdin can attenuate BD-induced lung injury by inhibiting pulmonary oxidative stress response and apoptosis. Key words: Biliverdine; Brain death; Respiratory distress syndrome,adult

Change of JNK and c-Jun in lung injury associated with paraquat poisoning of rats

To investigate the change of JNK and c-Jun in lung injury associated with paraquat poisoning of rats. 46 Rats were randomly divided into four groups: PQ group (n = 12), control group (n = 10), PQ + ZnPP group (n = 12) and PQ + Hm group (n = 12). The rats were injected with 2% PQ (25 mg/kg, ip) in PQ group. ZnPP and Hemin (10 mg/kg, 10 mg/ml) were injected through inguinal vein before intraperitoneal administration of 2% paraquat in PQ + ZnPP group and PQ + Hm group respectively. The rats were injected NS (1 ml/kg, ip) in control group. HE dyeing of lung tissue and MDA content of plasma were used for estimating the injury of lung tissue. The content of CO in the lung tissue was determined. The expression of HO-1 mRNA of the lung tissue was detected by the reverse transcription-polymerase chain reaction. The phosphorylation of JNK and c-Jun was evaluated by Western blot analysis. The degree of lung injury in PQ group and PQ + ZnPP group was higher than that in control group and PQ + Hm group. But in PQ + Hm group the degree of lung injury was lower. The content of MDA in PQ group and PQ + ZnPP group was higher than that in control group and PQ + Hm group (P < 0.01). The content of MDA in PQ + Hm group was higher than that in control group (P < 0.05). The content of CO in lung tissue in PQ group, PQ + ZnPP group and PQ + Hm group was and (1.08 +/- 0.15 mg/L) respectively, and higher than that in control group (P < 0.01). The content of CO in lung tissue in PQ + Hm group was significantly higher than that in PQ + ZnPP group (P < 0.01). The expression of HO-1 and the phosphorylation of JNK (55.24 +/- 9.34, 38.15 +/- 10.71, 128.55 +/- 19.43) and c-Jun (23.16 +/- 4.85, 15.49 +/- 3.13, 44.89 +/- 10.37) were increased remarkably in PQ group, PQ + ZnPP group and PQ + Hm group. Those in PQ + Hm group were higher significantly than PQ group and PQ + ZnPP group (P < 0.01). Those in PQ + ZnPP group were lower than PQ group (P < 0.05). The increase of CO of lung tissue in rats at the lung injury associated with paraquat poisoning reduces the acute lung injury of rats. The level of JNK and c-Jun phosphorylation increases obviously, especially after Hemin is utilized.

Protective Effects of Erdosteine and Vitamins C and E Combination on Ischemia–Reperfusion-Induced Lung Oxidative Stress and Plasma Copper and Zinc Levels in a Rat Hind Limb Model

The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia-reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats.

Melatonin reduces both basal and bacterial lipopolysaccharide-induced lipid peroxidation in vitro

The protective effect of melatonin against lipopolysaccharide (LPS)-induced oxidative damage was examined in vitro. Lung, liver, and brain malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) concentrations were measured as indices of induced membrane peroxidative damage. Homogenates of brain, lung, and liver were incubated with LPS at concentrations of either 1, 10, 50, 200, or 400μg/ml for 1 h and, in another study, LPS at a concentration of 400 μg/ml for either 0, 15, 30, or 60 min. Melatonin at increasing concentrations from 0.01–3 mM either alone or together with LPS (400μg/ml) was used. Liver, brain, and lung MDA + 4-HDA levels increased after LPS at concentrations of 10, 50, 200 or 400 μg/ml; this effect was concentration-dependent. The highest levels of lipid peroxidation products were observed after tissues were incubated with an LPS concentration of 400 μg/ml for 60 min; in liver and lung this effect was totally suppressed by melatonin and partially suppressed in brain in a concentration-dependent manner. In addition, melatonin alone was effective in brain at concentrations of 0.1 to 3 mM, in lung at 2 to 3 mM, and in liver at 0.1 to 3 mM; in all cases, the inhibitory effects of melatonin on lipid peroxidation were always directly correlated with the concentration of melatonin in the medium. The results show that the direct effect of LPS on the lipid peroxidation following endotoxin exposure is markedly reduced by melatonin.

Oxygen metabolite detoxifying enzyme levels in bleomycin-induced fibrotic lungs

The activities of three enzymes cytosolic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHP), and malonylialdehyde (MDA), a by-product of lipid peroxidation, were determined in whole lungs of normal and bleomycin-treated rats. Two days after bleomycin treatment total lung SOD, CAT, and GSHP activities were significantly ( p < .025) depressed between 15 and 25%. The activities of all three enzymes increased 4 days after bleomycin treatment with only SOD significantly increased at days 4 and 7. Total lung CAT activity remained near normal levels while GSHP activity increased only at day 28 (160.5%, p < .01) indicating a specificity of the response of lung SOD and GSHP levels. Total lung MDA levels were increased by 17% at 2 and 4 days ( p < .05) after bleomycin treatment, and returned to normal levels at 7 and 28 days. These data suggest that impairment of the lung's ability to detoxify O 2 metabolites may play an important role in the development of bleomycin-induced pulmonary fibrosis.