长期染砷致家兔肝脏蛋白巯基水平及巯基代谢相关酶活力下降

目的 探讨长期砷暴露对家兔肝脏蛋白巯基水平及与巯基代谢相关酶活力的影响及机制。方法 家兔以自由饮水方式慢性暴露于无机3价砷（iAs^Ⅲ）及5价砷（iAs^Ⅴ），18周后，测定肝脏组织中蛋白巯基、非蛋白巯基、硫氧还蛋白（TRX）水平，以及硫氧还蛋白还原酶（TR）、谷胱甘肽还原酶（GR）活性，同时检测血、尿及毛发中无机砷及其代谢产物甲基砷（MMAs）和二甲基砷（DMAs）。结果 经过18周的砷暴露，两个染毒组血和尿中iAs、MMAs、DMAs以及毛发中iAs、DMAs均显著高于对照组；iAs^Ⅴ组血中iAs、MMAs及尿中MMAs水平显著低于iAs^Ⅲ组，而尿及毛发中iAs水平显著高于iAs^Ⅲ组。iAs^Ⅴ组总巯基及蛋白巯基水平显著低于对照组。iAs^Ⅵ组TRX水平、TR及GR活力以及iAs^Ⅲ组TR活力与对照组相比亦显著下降。结论 家兔长期砷暴露导致肝脏中蛋白巯基水平及与巯基代谢密切相关的TR、GR活力显著下降，提示慢性无机砷暴露会引起肝脏内氧化及抗氧化失衡从而引发组织氧化损伤。     

The interrelation of glutathione reductase,catalase, glutathione peroxidase,superoxide dismutase,and glucose-6-phosphate in the pathogenesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis, a systemic autoimmune disease characterized by chronic inflammation of the synovial joints, ultimately leading to joint destruction and permanent disability, affecting 1% of the world population. Oxidative stress in rheumatoid inflammation, due to the fact that antioxidant systems are impaired in RA and caused by fee radicals, might have an essential role in etiology of RA. This review includes the interrelation of antioxidants against free radicals in RA patients. There is much evidence that antioxidant team that covers glutathione reductase, catalase, glutathione peroxidase, superoxide dismutase, and glucose-6-phopshate destroy reactive oxygen species and other free radicals through enzymatic as well as nonenzymatic means. The change in relative levels of antioxidants vis-à-vis free radical formation and level could be used as indicators for effective and earlier diagnosis of RA.     

砷中毒患者红细胞免疫功能与脂质过氧化的相关关系

目的 了解燃煤型砷中毒患者红细胞（RBC）免疫功能与脂质过氧化关系。方法 将燃煤型砷中毒患者分为轻、中、重3组，选择距病区12km外的非燃用砷煤居民作对照组，分别检测各组RBC免疫功能和血浆MDA、SOD、GSH-Px，并分别与对照组比较。结果 燃煤型砷中毒患者RBC免疫功能损伤RBC-ICR高于对照组，RBC-CbRR低于对照组，患者MDA高于对照组，而SOD、GSH-Px则低于对照组。结论 氧化自由基堆积造成脂质过氧化损伤，这可能是患者RBC免疫功能受损的重要原因。     

Proteasome inhibitor treatment in alcoholic liver disease

Oxidative stress, generated by chronic ethanol consumption, is a major cause of hepatotoxicity and liver injury. Increased production of oxygen-derived free radicals due to ethanol metabolism by CYP2E1 is principally located in the cytoplasm and in the mitochondria, which does not only injure liver cells, but also other vital organs, such as the heart and the brain. Therefore, there is a need for better treatment to enhance the antioxidant response elements. To date, there is no established treatment to att...     

N-(4-Hydroxyphenyl)retinamide (4-HPR) Induces Leukemia Cell Death via Generation of Reactive Oxygen Species

The role of reactive oxygen species (ROS) in the cytotoxicity of N-(4-hydroxyphenyl)retinamide (4-HPR) was studied with use of the B-precursor lymphoblastic leukemia cell line YCUB-2. The increase in intracellular ROS measured with 2'-7'-dichlorodihydrofluorescein diacetate after 3 hours' incubation was 3.7-fold with 1 microM 4-HPR and 5.8-fold with 5 microM 4-HPR. The rate of apoptosis after 48 hours' incubation was 9.8% and 56.4% in comparison with untreated cells. Hydroethidine, which is a more specific indicator of superoxide anion radical level, did not effectively detect 4-HPR-induced ROS. The antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one suppressed 4-HPR-induced ROS production and apoptosis. The cytotoxicity of 4-HPR was analyzed in 4 other leukemia/lymphoma lines (CCRF-HSB2, Molt-4, KG-1, HL-60). We found that the cytotoxicity of 4-HPR correlated with the amount of ROS produced in cell lines, except in HL-60 cells. The intracellular glutathione level varied among the 5 cell lines, the highest levels occurring in Molt-4 and KG-1, which were less sensitive to 4-HPR. Suppression of glutathione by buthionine sulfoximine enhanced the level of 4-HPR-induced ROS production and apoptosis in Molt-4. Our findings suggest that ROS play a significant role in the antileukemia effect of 4-HPR and that the glutathione level in leukemias may be associated the sensitivity of the cells to 4-HPR.     

Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro

Summary This study addresses the possibility that the teratogenic effects of a diabetic pregnancy are associated with increased embryonic activities of free oxygen radicals. Rat embryos were cultured in 50 mmol/l glucose for 48 h and subsequently showed pronounced growth retardation and severe malformations. The enzyme inducer citiolone and the free oxygen radical scavenging enzymes Superoxide dismutase, catalase and glutathione peroxidase protected against the disturbed growth and development of the embryos at 50 mmol/l glucose when added to the culture media. Enzymatic measurements indicated that citiolone induced an increased activity of superoxide dismutase in the embryonic tissues and that the added enzymes were taken up by both the yolk sac and the embryo proper. The protection against embryonic maldevelopment was thus conferred by agents that increased the free oxygen radical scavenging capacity of the embryonic tissues. The results suggest that a high glucose concentration in vitro causes embryonic dysmorphogenesis by generation of free oxygen radicals. An enhanced production of such radicals in embryonic tissues may be directly related to the increased risk of congenital malformations in diabetic pregnancy.This study was presented in part at the 26th Annual Meeting of the European Association for the Study of Diabetes, Copenhagen, Denmark, 10–14 September 1990     

高碘对大鼠甲状腺过氧化物酶和钠碘转运体基因mRNA表达的影响

目的 观察长期碘过量对大鼠甲状腺过氧化物酶(TPO)和钠碘转运体(NIS)mRNA表达的影响.方法 将SD大鼠按体质量随机分为对照(CI)组、高碘Ⅰ(HI Ⅰ)组、高碘Ⅱ(HIⅡ)组,分别饮用含碘5、5000、10000μg/L的自来水.6个月时取大鼠甲状腺,在光、电镜下观察甲状腺形态结构的变化;采用放射免疫法测定血清甲状腺激素水平;RT-PCR法检测甲状腺TPO、NIS mRNA的表达.结果 高碘组与CI组相比.部分甲状腺滤泡明显增大,滤泡腔内充满浓染胶质;血清TT4 、TT3水平,HI Ⅰ组[(73.82±16.48)、(1.34±0.31)nmol/L]和HIⅡ组[(70.65±11.43)、(1.15±0.39)nmol/L]与对照组[(75.68±13.99)、(1.45±0.49)nmol/L]相比呈逐渐下降趋势,但组间差异无统计学意义(F值分别为0.371、1.163,P＞0.05);TPO、NIS mRNA表达水平,组间比较差异有统计学意义(F值分别为30.863、62.675,P＜0.05).HI Ⅰ组(1.28±0.10、0.56±0.17)和HIⅡ组(1.14±0.04、0.39±0.06)均比对照组(1.39±0.08、0.71±0.13)明显降低(P＜0.05).结论 长期碘过量可造成甲状腺组织形态学改变,并且抑制甲状腺TPO、NIS mRNA表达.     

Insulin labelled by coupling with peroxidase

Summary By coupling purified horseradish peroxidase with glutaraldehyde and subsequent reaction with insulin, conjugates were obtained. These were partially purified by ion exchange chromatography on DEAE-cellulose. A fraction with an average molar ratio of peroxidase to insulin 1:0.37 was analysed by electrophoresis and gel filtration. The peroxidase activity of this fraction was found to be 19% of normal and the immunological reactivity 0.6% as compared with that of insulin.Kindly supported by Landesversicherungsanstalt Rheinprovinz, Düsseldorf, and Landesamt für Forschung, Nordrhein Westfalen.     

老年Ⅱ型糖尿病患者血过氧化脂质和抗氧化酶的检测及其临床意义

22例老年NIDDM患者和18例正常人检测结果显示,老年NIDDM的LPO显著升高,SOD、CAT、GSH-Px、Se-GSH-Px显著降低,LPO与上述四种抗氧化酶负相关;BG、TG、TC、LDL和ApoB显著升高,HDL显著降低;SOD与BG负相关;LPO与TG、TC、LDL正相关,与HDL、ApoA_1负相关。提示老年NIDDM患者LPO升高可能与其溏、脂代谢紊乱有关。LPO的持续升高可能是其心血管并发症发生的重要因素之一。     

Genetic modification of the effect of maternal household air pollution exposure on birth weight in Guatemalan newborns

Low birth weight is associated with exposure to air pollution during pregnancy. The purpose of this study was to evaluate whether null polymorphisms of Glutathione S-transferases (GSTs), specifically GSTM1 and GSTT1 genes in infants or mothers, modify the association between high exposures to household air pollution (HAP) from cooking fires and birth weight. Pregnant women in rural Guatemala were randomized to receive a chimney stove or continue to use open fires for cooking. Newborns were measured within 48 h of birth. 132 mother–infant pairs provided infant genotypes (n = 130) and/or maternal genotypes (n = 116). Maternal null GSTM1 was associated with a 144 g (95% CI, −291, 1) and combined maternal/infant null GSTT1 was associated with a 155 g (95% CI, −303, −8) decrease in birth weight. Although there was a trend toward higher birth weights with increasing number of expressed GST genes, the effect modification by chimney stove use was not demonstrated.