Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferases, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, γ-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for γ-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.     

Pathogenesis of progressive muscular dystrophy: studies on free radical metabolism in an animal model

Evidence to suggest the presence of abnormal metabolism of oxygen free radicals in progressive muscular dystrophy is presented using an animal model. In the superficial pectoral muscles of dystrophic chickens, enzyme activities regulating the metabolism of oxygen free radicals, i.e., catalase, superoxide dismutases and glutathione peroxidase, were significantly elevated within 1 week of hatching. Activities of related enzymes, i.e., glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase were also elevated. In contrast, the specific activity of phosphofructokinase, the rate-limiting enzyme of the glycolytic pathway, was normal during the first 4-week period. These results suggest that there is an increased turnover of oxygen free radicals in the dystrophic muscle. This concept appears important in a further investigation of the pathogenesis and treatment of progressive muscular dystrophies.     

用尿谷胱甘肽过氧化物酶评定颈椎病的康复疗效

测定了44例颈椎病患者康复前后尿液中谷胱甘肤过氧化物酶(GSH-Px)活力的变化。患者在治疗前,尿中GSH-Px活力为1080±310U/L((?)±s),与健康对照组相比差异有高度显著性(P<0.001)。推拿和颈牵治疗后尿中GSH—Px活力平均下降38.8%,且下降幅度和疗效之间有着明显的平行关系。据此,我们认为颈椎病的发病可能和体内自由基代谢紊乱有关,同时认为,无创伤的尿GSH—Px活力测定可以作为颈椎病康复疗效评定的客观指标,从而为颈椎病康复疗效的评定提供科学的生化依据。     

地尔硫对冠心病的抗氧化作用

目的：观察地尔硫对冠心病病人的抗脂质过氧化及抗氧自由基作用。方法：冠心病病人３０例为治疗组（男性２１例，女性９例，年龄５８±ｓ６ａ），给予地尔硫３０ｍｇ，ｐｏ，ｔｉｄ，共４ｗｋ。健康人组３０例（男性１８例，女性１２例，年龄５８±９ａ）。结果：治疗组在给药前较健康人组的血清ｏｘＬＤＬ，ＬＰＯ，ＳＣＬ，ＬＣＬ值显著升高，Ｐ＜０．０１，ＧＳＨ－Ｐｘ显著降低，Ｐ＜０．０１，ＳＯＤ活力两者无明显差异，Ｐ＞０．０５。治疗组用药后与用药前相比ｏｘＬＤＬ，ＬＰＯ，ＳＣＬ，ＬＣＬ值显著下降，Ｐ＜０．０１或＜０．０５，ＧＳＨ－Ｐｘ显著升高，Ｐ＜０．０１，治疗组治疗后与健康人组相比，除ＬＣＬ外，其他指标皆无明显差异，Ｐ＞０．０５。结论：地尔硫是一良好的抗氧化剂。     

Intrahepatic Delivery of Glutathione by Conjugation to Dextran

Glutathione was covalently attached to dextran (T-40) by the CNBr activation method. The compound obtained was a water-soluble powder containing 10 (w/w%) glutathione, which was gradually released from the conjugate in aqueous media. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of -glutamylcysteine synthetase, exhibited a significant increase in hepatic glutathione level after intravenous injection of the conjugate. In mice given a lethal dose of acetaminophen, the survival rate increased progressively with coadministration of the conjugate, whereas little improvement was found when free glutathione was given. The conjugate maintained the serum transaminase activities at lower level after acetaminophen administration. These findings suggest that the dextran conjugate of glutathione is transported into hepatic cells and is intracellulary hydrolyzed to free form, which protects mice from hepatotoxicity due to acetaminophen.     

Alterations of plasma antioxidants and mitochondrial DNA mutation in hair follicles of smokers

The effects of long-term smoking on mitochondrial DNA (mtDNA) deletions in hair follicles were investigated in subjects with different antioxidant capacity. Twenty-two male smokers with a smoking index of greater than 5 pack-years and without any known systemic diseases were recruited for this study. Forty healthy nonsmoking males were included as controls. We found that the concentrations of ascorbate and alpha-tocopherol and the activities of glutathione S-transferase (GST) and glutathione peroxidase in blood plasma were significantly decreased in smokers. The levels of glutathione and protein thiols in whole blood and the incidence of a 4,977 bp deletion of mtDNA (dmtDNA) in hair follicles were significantly increased in smokers. A significantly higher incidence of the 4,977 bp dmtDNA was found in smokers with plasma GST activity less than 5.66 U/l (OR = 7.2, P = 0.020). Using multiple covariate ANOVA and logistic regression, we found that age and low plasma GST activity were the only two risk factors for the 4,977 bp dmtDNA. These results suggest that smoking depletes antioxidants and causes mtDNA deletions and that plasma GST may play an important role in the preservation of the mitochondrial genome in tissue cells of smokers.     

Effects of sex hormones and antihormones on the activity of redox system enzymes of human erythrocyte glutathione

Effects of estradiol and testosterone and of the antiandrogens cyproterone acetate, niftolide, and antiestrogen tamoxifen on the activities of human erythrocyte glutathione peroxidase and glutathione reductase were studiedin vitro. In contrast to hormone preperations, antihormones in high concentrations (10⁻⁴−5×10⁻⁴ M) modified the enzyme activities. Cyproterone acetate and tamoxifen increased the activity of glutathione reductase, while tamoxifen stimulated glutathione reductase and inhibited glutathione peroxidase. Niftolide inhibited both enzymes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 185–187, August, 1997     

日本血吸虫大陆株26kDa谷胱甘肽S┐转移酶编码区基因的克隆及序列测定

从日本血吸虫大陆株成虫分离总ＲＮＡ，逆转录合成ｃＤＮＡ第一链，根据菲律宾株２６ｋＤａ谷胱甘肽Ｓ－转移酶（ＧＳＴ）的ｃＤＮＡ序列，设计并合成引物，扩增出２６ｋＤａ的编码区基因，并克隆到ｐＢｌｕｅｓｃｒｉｐｔ质粒。初步酶切鉴定后，从两端对插入片段进行核苷酸序列测定。结果与菲律宾株比较，核苷酸同源性为９９．８％，仅第５８２位碱基不同，菲律宾株为Ａ，而大陆株为Ｇ。比较从ｃＤＮＡ推导出的氨基酸序列，两者１００％相同。测序结果也与曼氏血吸虫进行了比较。