Objective To explore the potential protective effect in vivo of Edaravone, a free radical scavenger on model of acute lung injury in rats with sepsis. Methods Twenty-four male Wistar rats were randomly divided into three groups, ie. a control group( NS group) , a model group( LPS group) , a Edaravone treatment group( ED group) . ALI was induced by injecting LPS intravenously( 10 mg/ kg) in the LPS group and the ED group. Meanwhile the ED group was intravenously injected with Edaravone( 3 mg/ kg) . The NS group was injected with normal saline as control. The lung tissue samples were collected at 6 h after intravenous injection. The wet / dry ( W/D) weight ratio of lung tissue was measured. The levels of myeloperoxidase ( MPO) , malondialdehyde ( MDA ) and superoxide dismutase ( SOD) in lung tissue homogenate were assayed. The pathological changes and expression of nuclear factor-kappa B( NF-κB) in lung tissue were also studied. Results Compared with the NS group, The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the LPS group were significantly higher( all P lt; 0. 01) , and the level of SOD was apparently lower( P lt; 0. 01) . The W/D, pathological scores, NF-κB expression, MPO and MDA levels in the ED group were significantly lower than those in the LPS group( all P lt; 0. 01) and higher than those in the NS group( all P lt; 0. 01) . And the level of SOD in lung tissue of the ED group was higher than that in the LPS group and lower than that in the NS group ( P lt; 0. 01) . Conclusions Edaravone has protective effect on ALI rat model. The mechanismmay be related to its ability of clearing the reactive oxygen species, inhibiting the activation of the signal pathway of NF-κB and inflammatory cascade.
Objective Glucocorticoid is the main cause of non-traumatic avascular necrosis of femoral head. To explore the changes of reactive oxygen species (ROS) in the bone microvascular endothel ial cells treated with glucocorticoid so as to investigate the pathogenesis of steroid-induced avascular necrosis of femoral head. Methods The cancellous bone of femoral head was harvested from voluntary donators undergoing total hip arthroplasty, and then the bone microvascular endothel ial cells were isolated by enzyme digestion. The cells at passage 3 were cocultured with different concentrations of hydrocortisone (0, 0.03, 0.10, 0.30, and 1.00 mg/mL) for 24 hours. MTT assay was used for the inhibitory rate of cell prol iferation, flow cytometry for apoptosis rate, and fluorescence probe for the production of ROS and xanthine oxidase (XOD). Results At 2-3 days primary culture, the cells were spindle and arranged l ike cobbles and they reached confluence after 1 week. The inhibitory rates of cell prol iferation in 0.03, 0.10, 0.30, and 1.00 mg/mL groups were 20.22% ± 2.97%, 22.94% ± 4.52%, 43.98% ± 3.35%, and 78.29% ± 3.85%, respectively; and 2 high-concentration groups (0.30 and 1.00 mg/mL groups) were significantly higher (P lt; 0.05) than 2 low-concentration groups (0.03 and 0.10 mg/mL groups). The apoptosis rates in 0, 0.03, 0.10, 0.30, and 1.00 mg/mL groups were 0.10% ± 0.01%, 0.23% ± 0.02%, 1.83% ± 0.04%, 6.34% ± 0.11%, and 15.33% ± 0.53%, respectively; 2 high-concentration groups (0.30 and 1.00 mg/mL groups) were significantly higher (P lt; 0.05) than 0 mg/mL group. In 0, 0.30, and 1.00 mg/ mL groups, the ROS levels were 57.35 ± 7.11, 120.47 ± 15.68, and 166.15 ± 11.57, respectively, and the XOD levels were 0.017 9 ± 0.000 9, 0.028 3 ± 0.001 7, and 0.067 7 ± 0.004 1, respectively; there were significant differences in the levels of ROS and XOD among 3 groups (P lt; 0.05). Conclusion Increasing of ROS production in bone microvascular endothel ial cells can be induced by high concentration glucocorticoid, and it can result in cell injury
目的 观察黄芪三七合剂（Aamp;R）对肾缺血再灌注损伤（IRI）大鼠血液活性氧（ROS）变化的影响，探讨其抗IRI损伤的机制。 方法 雄性Sprague-Dawley（SD）大鼠30只，随机分为正常组（n=5）、假手术组（SG）（n=5）和IRI 24 h组（n=10），Aamp;R组（n=10）。造模：采用微血管夹夹闭双侧肾蒂，22 min后松开动脉夹，用5/0尼龙缝合线缝合腹部。再灌注24 h后将小鼠行麻醉处死。Aamp;R组给予Aamp;R（3 mL/d），假手术组及IRI 24 h组给予同等体积的生理盐水。采用全自动生化分析仪检测各组大鼠的肾功能，苏木精-伊红染色了解肾脏病理损害，流式细胞仪检测红细胞ROS。 结果 IRI 24 h组和Aamp;R组肾小管出现不同程度的管腔扩张、变性与坏死，间质炎性细胞浸润、充血水肿等变化。IRI后24 h时，IRI 24 h组、Aamp;R组血清尿素氮（BUN）和肌酐（Cr）均高于假手术组、正常组，差异有统计学意义（P＜0.05）；Aamp;R组ROS荧光强度阳性率显著低于IRI 24 h组，差异有统计学意义（P＜0.05）。Aamp;R组肾小管损伤评分明显低IRI 24 h组（P＜0.05）。相关性分析发现，红细胞ROS荧光强度阳性率与肾小管损伤评分、肌酐、尿素氮水平成正相关（r=0.917，P＜0.01；r=0.897，P＜0.01；r=0.896，P＜0.01）。 结论 Aamp;R对肾脏缺血再灌注损伤具有明显的保护作用，其机制可能为抑制血液中ROS的活性，从而抑制氧化应激对肾脏的损伤。
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the development and use of several targeting drugs for lung cancer therapy, the five-year survival rate has remained as low as 15% for the past three decades. Cisplatin-based chemotherapy is considered the first-line therapeutic strategy for lung cancer. However, developments of chemoresistance is a major obstacle for the successful treatment. Therefore, the development of novel therapy against cisplatin-resistance lung cancer is imperative. Photodynamic therapy (PDT), which is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS) and oxygen, may provide an unprecedented tool to develop more effective treatments. To provide experimental basis for its application in cisplatin-resistance lung cancer, we will discuss the biological effects of MPPa-photodynamic therapy in human cisplatin-resistance lung cancer cells in this article. Human cisplatin-resistance lung cancer cells A549/DDP were co-cultured with MPPa (0, 1, 2, 4, 8, 16 μmol/L) and exposed to light (0, 0.6, 1.2, 2.4, 3.6, 4.8 J/cm2), and cell viability was determined with CCK-8 assay. Flow cytometry was used to detect apoptosis, DCFH-DA staining was employed to observe reactive oxygen species (ROS), and Western blot was used to detect the expressions of B-cell lymphoma-2 (Bcl-2) protein and Bcl-2 associated X protein (Bax). The proliferation of A549/DDP cells was suppressed by PDT. The apop-totic rate in the PDT group was significantly higher than that in the control, MPPa or light group (P < 0.05). The level of ROS was increased. The expression of Bax was increased, and that of Bcl-2 was decreased. MPPa-photodynamic therapy can significantly suppress cell viability, and induce apoptosis in human cisplatin-resistance lung cancer cells.
ObjectiveTo review the recent research progress about the pathogenesis and prevention of reactive oxygen species (ROS) in the hepatic ischemia-reperfusion injury (HIRI). MethodsSearched the related literatures in recent years from the databases such as CNKI, PubMed and so on, summarized the recent research progress about the generation mechanism of ROS, the damage mechanism of ROS, and the prevention method of ROS. ResultsA mass of ROS originated from polymorphonuclear leukocytes, Kupffer cells, mitochondria, and the enzymes in hepatic tissue in HIRI. It mainly destroyed sugar molecules of oligosaccharide chains on the cell membrane, unsaturated fatty acid, protein molecules, mitochondrial, and genetic material. This mechanism lead to cell injuried or even death. The main method of prevention and cure to HIRI is eliminating ROS by using enzymes, vitamins, Chinese herbal medicines etc. ConclusionsThe research about ROS in HIRI has advanced. Aiming at the damage resulted from ROS in the liver, Scholars have came up with a variety of control methods which is feasible. However, many issues need to be further investigated.
ObjectiveTo investigate the effects of leptin on the oxidative damage in human retinal pigment epithelial (RPE) cells. MethodsHuman RPE cells (ARPE-19) were cultured in vitro, and randomly divided into control group and insulin resistance group. RPE cells were treated with 0, 10, 100 ng/mL leptin for 24, 48, 72 hours respectively. Then the levels of reactive oxygen species (ROS) expression in RPE cells were detected by 2', 7'-dichlorofluorescin-diacetate (DCFH-DA), and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression in RPE cells were observed by immunocytochemistry (ICC), and the levels of human 8-oxoguanine DNA glycosylase l (hOGG1) expression in lysate were measured by Western blot. ResultsAfter 24, 48, 72 hours, the level of ROS (Control group:F=37.136, 37.178, 49.634; P < 0.05. Insulin resistance group:F=9.822, 28.881, 71.150;P < 0.05), 8-OHdG (Control group:F=88.643, 390.920, 1039.276;P < 0.05.Insulin resistance group:F=273.311, 299.155, 82.237;P < 0.05) and hOGGl (Control group:F=470.062, 1073.113, 295.456;P < 0.05. Insulin resistance group:F=240.032, 592.389, 527.760;P < 0.05) expression increased significantly with the increase of leptin concentration in control group and insulin resistance group. Under the same leptin concentration, the level of 8-OHdG has a trend that it was higher in the insulin resistance group than the control group. After 24 hours, the difference of hOGGl expression between control group and insulin resistance group was not significant (F=23.392, P > 0.05). After 72 hours, the level of hOGGl expression was significantly higher in the insulin resistance group than the control group (F=129.394, P < 0.05). The level of hOGGl expression was significantly higher at 48 hours than that at 24 hours and 72 hours (P < 0.05). ConclusionLeptin could induce the oxidative damage of RPE cells in normal and insulin resistance status. With the increase of leptin concentration and time extended, the degree of oxidative damage and its repair were both increased. The degree of oxidative repair increased with the increase of leptin concentration, but decreased with time extended.
Objective To investigate the expression of heme oxygenase-1 (HO-1) by high glucose treatment in human lung epithelial A549 cells. Methods The effect of high glucose on the expression of HO-1 in A549 cells was investigated with Western blot and reverse transcription PCR. HO-1 enzymic activity and reactive oxygen species (ROS) production were investigated with enzyme-linked immunosorbent test. Results Treatment with 25 mmol/L high glucose for 0, 24 h, 48 h, 72 h and in concentrations of 5 mmol/L, 10 mmol/L, 25 mmol/L, 40 mmol/L for 48 h induced increased expression on protein and mRNA level of HO-1 in a concentration- and time-dependent manner in A549 cells. High glucose treatment increased production of ROS and transforming growth factor-β1 (TGF-β1) in A549 cells, which thus mediated HO-1 expression. Following the increase in HO-1 expression, the enzymatic activity of HO-1 also increased in high glucose-treated cells. Pretreatment with N-acetyl-L-cysteine (NAC) and PI3K/Akt inhibitors attenuated the high glucose-induced increased HO-1 expression. Conclusions High glucose increases ROS and TGF-β1 production in A549 cells, which mediates HO-1 expression and increases HO-1 enzymic activity.
To aggressively proliferate and metastasize, cancer cells are in extreme need of energy supply and nutrients. Therefore, a promising cancer therapy strategy is developed to target its hallmark feature of metabolism. Recent findings revealed the regulatory role of caveolin-1 (Cav-1), a structural protein of caveolae, in cancer metabolism. And low Cav-1 expression in tumor stroma was proved to be a central player of cancer malignant phenotype. Here, we summarized the progressions of studies on Cav-1, mitochondria and cancer metabolism to indicate that the altered metabolism induced by Cav-1 and mitochondria association is a major cause of cancer malignant phenotype.