N-acetyl-L-cysteine reduces the ozone-induced lung inflammation response in mice / 生理学报

In this study, we investigated the protective effect of the antioxidant N-acetyl-L-cysteine (NAC) on the lung inflammation caused by ozone (O) exposure in mice. Thirty-two C57BL/6 mice were randomly divided into control group, Ogroup, O+NAC group and NAC group. Mice were exposed to O(1.0 ppm) or fresh air for 3 h on the day 1, day 3 and day 5, respectively. NAC (100 mg/kg) was intraperitoneally applied to the mice 1 h before each exposure. At 24 h after the 3-time exposure, the alveolar wall structure was severely damaged and the infiltrated inflammatory cells were apparent perivascularly and peribronchiolarly. Significant increases in the total white blood cell count, macrophage, lymphocyte and neutrophil counts, as well as total protein concentration were observed in the bronchoalveolar lavage fluid (BALF) (P < 0.05). The IL-6, IL-8 (P < 0.01) and MDA levels (P < 0.05) in the lung homogenates were elevated coherently. Administration of NAC could attenuate the alveolar wall structure damage induced by Oexposure and reduce the amount of infiltrated inflammatory cells, total and differential leukocyte counts (P < 0.05), as well as the IL-6, IL-8 (P < 0.01) and MDA release (P < 0.05). Western blotting results showed that the Oexposure up-regulated the p38 MAPK and NF-κB p65 protein expression in the lung tissue of mice (P < 0.05), which could be alleviated by NAC (P < 0.05). These results indicated that NAC could protect against O-induced pulmonary inflammation in mice. The beneficial effect of NAC might be related with the p38 MAPK and NF-κB p65 signal pathway.

Role of NADPH oxidase in endothelial cell dysfunction induced by endothelial microparticles / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the correlation between circulating endothelial microparticles (EMPs) and flow-mediated dialation (FMD) in patients with coronary artery disease (CAD), and investigate the role of NADPH oxidase in endothelial cell dysfunction caused by EMPs.</p><p><b>METHODS</b>Fifteen patients with CAD and 15 at high risks of CAD were tested for the level of EMPs and FMD and other biochemical indices, and the correlation between the indices were analyzed. EMPs obtained from cultured human umbilical vein endothelial cells (HUVECs) were phenotyped and used to stimulate the HUVECs, whose ROS and NO production was tested.</p><p><b>RESULTS</b>Endothelial dilation function could be damaged by circulating EMPs in CAD patients. Dysfunction of HUVECs caused by 10(5)/ml EMPs could be reversed by pretreatment with 20 micromol/L apocynin, a NADPH oxidase inhibitor.</p><p><b>CONCLUSION</b>Endothelial dialation function of the endothelial cells can be damaged by circulating EMPs in patients with CAD in association with NADPH oxidase activation.</p>

ERK1/2 mediates edaravone-triggered protection against myocardial damage induced by isoprenaline in H9c2 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of extracellular signal regulated kinase 1/2 (ERK1/2) on edaravone (EDA)-triggered protection against myocardial toxicity induced by isoprenaline (ISO) in H9c2 myocardial cells (H9c2 cells).</p><p><b>METHODS</b>H9c2 cells were exposed to ISO at different concentrations to establish a cardiac toxicity model induced by persistent excitation of β1 receptor. EDA was added before ISO as a pretreatment. PD-98059, an ERK1/2 inhibitor, was administered 1 h prior to EDA to inhibit the phosphorylation of ERK1/2. Cell viability was measured using cell counter kit (CCK-8). The expressions of p-ERK1/2 and t-ERK1/2 were tested by Western blotting. Mitochondrial membrane potential (MMP) was detected by Rhodamine123 (Rh123) staining and photofluorography.</p><p><b>RESULTS</b>Exposure of H9c2 cells to 80 µmol/L ISO for 24 h down-regulated ERK1/2 phosphorylation and repressed MMP. Pretreatment with 10-40 µmol/L EDA for 1 h inhibited ISO-induced myocardial toxicity and pretreatment of 40 µmol/L EDA partially rescued ERK1/2 phosphorylation and MMP level. PD-98059 abolished cardiac protection of EDA, leading to myocardial toxicity and MMP loss.</p><p><b>CONCLUSION</b>EDA can protect H9c2 cells against myocardial injury induced by ISO by suppressing ISO-triggered inhibition of ERK1/2 activation.</p>

Reactive oxygen species scavenger protects cardiac cells against injuries induced by chemical hypoxia / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of reactive oxygen species (ROS) scavenger, N-acetyl-L-cysteine (NAC), against H9c2 cardiomyocytes from injuries induced by chemical hypoxia.</p><p><b>METHODS</b>H9c2 cells were treated with cobalt chloride (CoCl2), a chemical hypoxia-mimetic agent, to establish the chemical hypoxia-induced cardiomyocyte injury model. NAC was added into the cell medium 60 min prior to CoCl2 exposure. The cell viability was evaluated using cell counter kit (CCK-8), and the intercellular ROS level was measured by 2', 7'- dichlorfluorescein-diacetate (DCFH-DA) staining and photofluorography. Mitochondrial membrane potential (MMP) of the cells was observed by Rhodamine123 (Rh123) staining and photofluorography, and the ratio of GSSG/ (GSSG+GSH) was calculated according to detection results of the GSSG kit.</p><p><b>RESULTS</b>Exposure of H9c2 cardiomyocytes to 600 micromol/L CoCl2 for 36 h resulted in significantly reduced cell viability. Pretreatment with NAC at the concentrations ranging from 500 to 2000 micromol/L 60 min before CoCl2 exposure dose-dependently inhibited CoCl2-induced H9c2 cell injuries, and obviously increased the cell viability. NAC at 2000 micromol/L obviously inhibited the oxidative stress induced by CoCl2, decreased the ratio of GSSG/(GSSG+GSH), increased ROS level, and antagonized CoCl2-induced inhibition on MMP.</p><p><b>CONCLUSION</b>NAC offers obvious protective effect on H9c2 cardiomyocytes against injuries induced by chemical hypoxia by decreasing in the ratio of GSSG/(GSSG+GSH) and ROS level and ameliorating MMP.</p>

Effects of angiotensin-(1-7) on oxidative stress and functional changes of isolated rat hearts induced by ischemia-reperfusion / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of angiotensin (Ang)-(1-7) on oxidative stress and functional changes in isolated rat hearts with myocardial ischemia-reperfusion (IR) injury.</p><p><b>METHODS</b>IR injury was induced in isolated rat hearts with the Langendorff' apparatus. The left ventricular systolic pressure (LVSP) of the rat heart was measured using a pressure transducer. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in the myocardium were detected using commercial kits.</p><p><b>RESULTS</b>Myocardial ischemia (15 min) and reperfusion (30 min) significantly increased myocardial levels of MDA, and reduced the SOD activity and LVSP (P<0.05). Pretreatment with Ang-(1-7) at 1.0 nmol/L 30 min before ischemia obviously inhibited IR-induced MDA increment and lowering of SOD activity and LVSP. Pretreatment of the rats with intraperitoneal injection of 5 mg/kg indomethacin 1 h before isolation of the heart markedly antagonized the effect of Ang-(1-7) on MDA production, SOD activity and LVSP.</p><p><b>CONCLUSION</b>Angiotensin-(1-7) can inhibit IR injury-induced oxidative stress and decrease in cardiac contractile function in isolated rat hearts. The mechanism underlying the effect of Ang-(1-7) may be associated with increased secretion of prostaglandin.</p>