支气管哮喘患儿红细胞免疫功能与脂质过氧化关系的探讨

目的 :探讨了支气管哮喘患儿红细胞免疫功能的变化及其与脂质过氧化的关系。方法 :应用红细胞酵母花环法测定了 32例支气管哮喘患儿红细胞免疫功能和化学比色法测定血浆丙二醛 (MDA) ,超氧化物歧化酶 (SOD) ,谷胱甘肽过氧化物酶 (GSH -PX)含量 ,并与 35名正常健康儿童作对照。结果 :支气管哮喘患儿RBC-IC花环率和MDA水平明显地升高 (P <0 .0 1 ) ,而RBC -C3bR、SOD、GSH -PX、SOD/MDA低于正常 (P <0 .0 1 ) ,相关分析显示 :RBC -C3b花环与MDA呈显著的负相关 (r=- 0 .4 30 7,P <0 .0 5 ) ,RBC -ICR与MDA呈正相关 (r=0 .6 384 ,P <0 .0 1 )。结论 :支气管哮喘患儿红细胞免疫粘附功能降低 ,与活性氧代谢紊乱密切相关     

Increased prooxidant production and enhanced susceptibility to glutathione depletion in HepG2 cells co-expressing HCV core protein and CYP2E1

Hepatitis C virus (HCV) and HCV core protein are hypothesized to induce hepatic oxidative stress and exacerbate injury caused by other toxins such as ethanol that induce the cytochrome P450 enzyme, CYP2E1. In the current study, the effects of HCV core protein [sequence genotype 1b, (nt 342-915)] on parameters indicative of oxidative stress were evaluated in HepG2 cells stably over expressing CYP2E1 (E47), or vector controls (C34). Stable (>10 passages) expression of HCV core protein and CYP2E1 was confirmed in clonal cell lines at the level of mRNA and immunoreactive protein. Prooxidant production, as determined by cellular oxidation of dichlorodihydrofluorescin and dihydroethidium (HE), was increased by expression of HCV core protein in the presence or absence of CYP2E1. Depletion of glutathione (GSH) with buthionine sulfoximine (BSO) enhanced prooxidant production in both C34 and E47 cells. In addition, prooxidant production was greater in BSO-treated cells expressing HCV core protein, and this effect was further enhanced in cells expressing both HCV core and CYP2E1. The CYP2E1 inhibitor, 4-methylpyrazole, could suppress increased prooxidant production in E47 cells. Finally, cells co-expressing both CYP2E1 and HCV core protein showed significantly decreased viability following GSH depletion. These studies show simultaneous expression of HCV core protein and CYP2E1 increases parameters indicative of oxidative stress as well as sensitization to cell injury induced by GSH depletion. These results support the hypothesis that enhanced injury in hepatocytes over expressing both HCV core protein and CYP2E1 is mediated by increases in oxidative stress.     

Elevation of plasma thioredoxin levels in HIV-infected individuals

Thioredoxin (Trx), a ubiquitous protein intimately involvedin redox and protein disulfide reductions, has been shown tobe released from cells and to have cytokine-like activities.In addition, Trx has been implicated in the redox regulationof immunological responses and shown to be deficient in tissuesfrom AIDS patients. In studies presented here, plasma Trx levelswere measured by ELISA in plasma samples from HIV-infected individuals(n = 136) and HIV-negative controls (n = 47). To account forthe release of Trx into plasma due to hemolysis, the Trx measurementswere corrected according to the level of hemoglobin in the plasmasample. Data presented show that, in contrast to tissue Trxlevels, corrected plasma Trx levels are significantly higherin HIV-infected individuals than in controls (P < 0.0001).Furthermore, {small tilde}25% of the HIV-infected individualsstudied have plasma Trx levels greater than the highest levelfound in controls (37 ng/ml). Detailed multiparameter FACS analysisof peripheral blood mononuclear cells (PBMC) from the infectedindividuals demonstrates that those with higher plasma Trx levels(37 ng/ml or greater) tend to have lower overall CD4 counts.In addition, increases in plasma Trx levels correlate with decreasesin monochlorobimane staining (indicative of lower intracellularglutathione levels in PBMC) and with changes in surface antigenexpression (CD62L, CD38 and CD20) that occur in the later stagesof HIV infection. These correlations suggest that elevationof plasma Trx levels may be an important component of advancedHIV disease, perhaps related to the oxidative stress that oftenoccurs at this stage.     

Effect of nonsurgical periodontal therapy on crevicular fluid and serum glutathione peroxidase levels

Background: Plasma glutathione peroxidase (eGPx) is an important selenium containing antioxidant in human defense against oxidative stress. While crevicular fluid (GCF) eGPx levels and its association with periodontal disease is well documented, there is no data on correlation of GCF and serum eGPx levels in chronic periodontitis. Hence this study was undertaken to further probe into the role of oxidative stress in periodontal diseases and effect of nonsurgical periodontal therapy (NSPT) by correlating GCF and serum levels of eGPx. Materials and methods: Thirty subjects (16-Males and 14-Females; age: 30–38 years) participated in the study. The subjects were divided, based on gingival index, probing pocket depth and clinical attachment level into: Healthy (group-1, n=10), Gingivitis (group-2, n=10) and Periodontitis (group-3, n=10). Chronic periodontitis patients after NSPT constituted group 4. GCF and serum samples collected from each subject were quantified for eGPx levels using Enzyme linked Immunosorbent Assay. Results: The mean eGPx concentrations increased from health (14.01 ng/μl and 78.26 ng/ml) to gingivitis (22.86 ng/μl and 90.44 ng/ml) and then to periodontitis (29.89 ng/μl and 103.43 ng/ml), in GCF and serum respectively. After NSPT, there was statistically significant reduction in eGPx concentration in GCF and serum (19.41 ng/μl and 85.21 ng/ml). Further, all the GCF eGPx values showed a positive correlation to that of serum eGPx level. Conclusion: Thus, increased eGPx concentration in GCF can be considered as an indicator of local increase in oxidative stress. While, increase in serum eGPx levels indicates that periodontal disease can also lead to increased oxidative stress at the systemic level.     

Glutathione S-transferase: differential expression of alpha, mu, and pi isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma

Glutathione S-transferases (GST) comprise a family of enzymes which are critical for inactivation of toxins and carcinogens. We examined the cellular expression of multiple subclasses of GST immunohistochemically in 25 radical prostatectomy specimens with clinically localized prostate cancer. Gleason scores ranged from 5 to 9, and pathologic stages varied from pT2a to pT3b (all N0M0). Antibodies were directed against GST Ya, Yc, and Yk (alpha subclass), Yb1 (micro subclass), and YPr (pi subclass). The percentage of positive cells and intensity of staining was assessed for benign epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. GSTalpha (Ya) was detected in 30% of cells (mean) in benign acini, 4.9% of cells in high-grade PIN, and 4.5% of cells in adenocarcinoma. The corresponding results for alpha (Yk), micro (Yb1), and pi (Yp) were 12.7%, 10.9%, and 3.5%; 8.7%, 5.2%, and 0.6%; and 66.7,% 0%, and 0%, respectively. GST Yc (alpha subclass) displayed the lowest level of expression, with diffuse weak staining in scattered benign secretory cells and only single cells (<1%) in high-grade PIN and carcinoma. These results demonstrate consistent reduction or loss of expression of all subclasses of GST with progression of prostatic neoplasia from benign epithelium to high-grade PIN and carcinoma. We hypothesize that carcinogenesis in the prostate results from impaired cellular handling of mutagenic agents owing to reduction or loss of expression of multiple GST and other detoxifying and antimutagenesis agents.     

Imbalance in the antioxidant defense system as a possible cause of decreased compensatory and adaptive reserves in youths with mitral valve prolapse

An imbalance in the first line of the antioxidant defence and hyperactivity of the glutathione-dependent system were revealed in 137 youths with mitral valve prolapse. Increased activities of superoxide dismutase and glutathione reductase (by 6 and 1.82–2.10 times, respectively) can serve as an additional diagnostic criterion of decreased compensatory reserves in patients with mitral valve prolapse. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 5, pp. 519–521, May, 2007     

Increased oxidative stress is associated with balanced increases in hepatocyte apoptosis and proliferation in glycerol-3-phosphate acyltransferase-1 deficient mice

The absence of mouse mitochondrial glycerol-3-phosphate acyltransferase-1 (Gpat1-/-) increases the amount of arachidonate in liver phospholipids and increases beta-hydroxybutyrate and acyl-carnitines, suggesting an elevated rate of liver fatty acid oxidation. We asked whether these alterations might increase reactive oxygen species (ROS), apoptosis, or hepatocyte proliferation. Compared to wildtype controls, liver mitochondria from Gpat1-/- mice showed a 20% increase in the rate of ROS production and a markedly increased sensitivity to the induction of the mitochondrial permeability transition. Mitochondrial phosphatidylethanolamine and phosphatidylcholine from Gpat1-/- liver contained 21% and 67% more arachidonate, respectively, than wildtype controls, and higher amounts of 4-hydroxynonenal, a product of arachidonate peroxidation. Oxidative stress was associated with an increase in apoptosis, and with 3-fold and 15-fold higher TUNEL positive cells in liver from young and old Gpat1-/- mice, respectively, compared to age-matched controls. Compared to controls, bromodeoxyuridine labeling was 50% and 7-fold higher in livers from young and old Gpat1-/- mice, respectively, but fewer glutathione-S-transferase positive cells were present. Thus, Gpat1-/- liver exhibits increased oxidative stress and sensitivity of the mitochondrial permeability transition pore, and a balanced increase in apoptosis and proliferation.     

肾病综合征患者红细胞免疫功能与脂质过氧化关系的探讨

目的：探讨了肾病综合征患者红细胞免疫功能与脂质过氧化的关系。方法：应用红细胞酵母花环法测定了31例肾病综合征患者的红细胞免疫功能和化学法测定血清丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）含量,并与35名正常健康人作比较。结果：肾病综合征患者RBC-ICR花环率和MDA水平明显升高（P〈0.01）,而RBC-C3bR,SOD,GSH-PX水平则〈正常（P〈0.01）,相关分析显示：RBC-C3b花环与MDA呈显著负相关（r=-0.4786,P〈0.01）,RBC-ICR与MDA呈正相关（r=0.6702,P〈0.01）。结论：肾病综合征患者红细胞免疫黏附功能的降低与活性代谢紊乱密切相关。     

母鼠注射麻黄素对仔鼠肝组织结构和总抗氧化能力、谷胱甘肽转移酶活性及丙二醛含量的影响

目的:探讨妊娠或哺乳期女性食用麻黄素对胎幼儿的影响。方法:给妊娠和哺乳期母鼠连续腹腔注射不同剂量(2、4、6 g/L)的麻黄素溶液,用分光光度法检测仔鼠肝组织总抗氧化能力(T-AOC)、谷胱甘肽转移酶(GST)活性及丙二醛(MDA)含量的变化,生物显微技术观察仔鼠肝组织结构的变化。结果:麻黄素组仔鼠肝组织结构出现不同程度的病理性变化,肝血窦扩张,并有内皮细胞脱落、肝板萎缩等现象,仔鼠肝组织T-AOC、GST活性降低,肝组织MDA含量升高,与对照组比较差异有统计学意义。结论:母鼠注射麻黄素会影响仔鼠肝组织结构和功能,麻黄素及其代谢物可能经胎盘或乳汁进入仔鼠体内损伤仔鼠肝组织的抗氧化系统,机体脂质过氧化反应增强,影响细胞的能量代谢。     

Effects of various medicinal forms of progesterone on lipid peroxidation and glutathione redox system in skin tissues of rats with experimental dermatitis

Activity of glutathione redox system in the dermis and epidermis decreased and the intensity of lipid peroxidation increased in rats with experimental dermatitis. Progesterone normalized these parameters. The most optimal treatment was subcutaneous injections of the hormone in a dose of 7×10⁻⁹ mol/100g. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 2, pp. 186–188, February, 2000