首发精神分裂症患者脂质过氧化物及抗氧化酶水平的研究

目的：探讨氧化应激在精神分裂症发病中的作用。方法：对首发且未服药的精神分裂症患者40例,行简明精神病评定量表（BPRS）评定,并测定氧化应激相关指标。药物治疗12周后,再次进行上述检测。取40例健康志愿者外周血,检测相同生化指标。结果：患者组丙二醛（MDA）和过氧化氢酶（CAT）较对照组显著升高（P〈0.01）,而超氧化物歧化酶（SOD）及谷胱甘肽过氧化物酶（GSH-Px）显著降低（P〈0.01）。治疗后MDA和CAT较治疗前显著降低（P〈0.01）,而SOD及GSH-Px显著升高（P〈0.01）。结论：精神分裂症患者处于氧化应激状态,自由基增加,抗氧化能力降低,这些可能与精神分裂症的病理机制有关。     

Changes in antioxidant enzymes in humans with long-term exposure to pesticides

Different pesticides, including organophosphates (OPs), have been reported to induce oxidative stress due to generation of free radicals and alteration in antioxidant defence mechanisms. In this study, a cohort of 81 intensive agriculture workers (pesticide sprayers) was assessed twice during the course of a spraying season for changes in erythrocyte antioxidant enzymes. Acetylcholinesterase (AChE) was used as a reference biomarker. Sprayers presented lower levels of superoxide dismutase (SOD) and glutathione reductase (GR) as compared to controls independently of age, BMI, smoking habit or alcohol consumption. A positive correlation between SOD and AChE was observed at the high exposure period. Those individuals with a decrease in AChE greater than 15% exhibited lower SOD and catalase (CAT) activities at the same period. Glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) remained unaffected in the exposed population. Paraoxonase (PON1) polymorphism influenced erythrocyte CAT and GR, as subjects with the R allele presented lower CAT and higher GR levels. Whether or not the decreased enzyme activities found in this study are linked to the adverse health effects related to chronic pesticide toxicity (in which oxidative damage plays a pathophysiological role, such as cancer or neurodegenerative disorders) is an attractive hypothesis that warrants further investigation.     

Capsaicin prevents ethanol-induced teratogenicity in cultured mouse whole embryos

Prenatal exposure to alcohol promotes the level of reactive oxygen species within embryos and results in developmental disorders. In this study, we investigated the effect of capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), the major pungent ingredient in red peppers, on ethanol-induced teratogenicity in mouse embryos (embryonic days 8.5-10.5). In response to ethanol administration (1.0 microl/ml), developmental parameters such as yolk sac circulation, allantois, heart, hindbrain, midbrain, forebrain, otic and optic systems, branchial bar, olfactory system, forelimb, hindlimb, and somites decreased significantly in comparison with those of control group (p<0.05). However, the concurrent administration of capsaicin (1 x 10(-8) microg/ml or 1 x 10(-7) microg/ml) and ethanol significantly ameliorated most of the morphological scores excepting yolk sac circulation and hindlimb scores (p<0.05). Furthermore, the levels of superoxide dismutase activity and cytoplasmic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase mRNAs in the ethanol-treated embryos recovered to the levels observed in control embryos by capsaicin co-administration. These results indicate that capsaicin has a protective effect against ethanol-induced teratogenicity via an antioxidative activity.     

Effect of N-acetylcysteine administration on the expression and activities of antioxidant enzymes and the malondialdehyde level in the blood of lead-exposed workers

We investigated whether treatment with N-acetylcysteine (NAC) reduces oxidative stress intensity and restores the expression and activities of superoxide dismutase (Sod1, SOD), catalase (Cat, CAT) and glutathione peroxidase (Gpx1, GPx) in lead-exposed workers.The exposed population was divided randomly into two groups. Workers in the first group (reference group, n = 49) were not administered any drugs, while workers in the second group (n = 122) were treated with NAC at three doses for 12 weeks (200 mg, 400 mg, 800 mg/day).NAC administered orally to lead-exposed workers normalized antioxidant enzyme activities in blood cells. Oxidative stress intensity measured as malondialdehyde (MDA) levels in serum, leukocytes and erythrocytes significantly decreased after NAC administration. NAC may be an alternative therapy for chronic lead intoxication.     

Effects of styrene and styrene oxide on glutathione-related antioxidant enzymes

Styrene is both hepatotoxic and pneumotoxic in mice. Its mode of action is not clear, but it may be related to oxidative stress including a very large decrease in reduced glutathione (GSH). The current studies evaluated if: (1) the more toxic R-styrene oxide had a greater effect on reduced GSH levels than the less toxic S-styrene oxide, (2) the ratio of reduced to oxidized forms of glutathione was altered by styrene or styrene oxide, (3) other enzymes involved in the oxidant status of the cell, namely glutathione reductase, glutathione peroxidase and gamma-glutamylcysteine synthetase were altered, and (4) lipid peroxidation, as measured by the determination of malondialdehyde, increased. R-Styrene oxide (300mg/kg, ip) caused greater decreases in mouse liver and lung GSH than did S-styrene oxide (300mg/kg, ip). Styrene (600mg/kg, ip) caused decreases in both GSH and GSSG in both liver and lung. Styrene and styrene oxide did not cause significant increases in lipid peroxidation in either liver or lung. Styrene and styrene oxide had minimal effects on glutathione reductase and glutathione peroxidase in liver and lung. Styrene increased gamma-glutamylcysteine synthetase activity. The results suggest that while styrene and its metabolite styrene oxide cause significant decreases in GSH levels, they have little effect on the enzymes glutathione reductase and glutathione peroxidase and that in response to decreased glutathione levels there is an increase in its synthesis via induction of gamma-glutamylcysteine synthetase activity.     

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.     

还原型谷胱甘肽治疗急性脑梗死的疗效观察

OBJECTIVETo explore the protective role of reduced glutathione(GSH) in actue cerebral infarction. METHOD60 patients were divided into two groups randomly:group GLT and group usually treatment .Serum glutathione peroxidase (GSH-PX) and superoxide dismutas     

Responses of antioxidant system in Arabidopsis thaliana suspension cells to the toxicity of microcystin-RR

Microcystins are cyclic heptapeptide hepatoxins produced by many species of cyanobacteria. The toxic effects and mechanism of microcystins on animals have been well studied both in vivo and in vitro. It was also reported that microcystins had adverse effects on plants. However, to our knowledge, there is no information about the toxic effects and mechanism of microcystins on plant suspension cells. In this study, Arabidopsis thaliana suspension cells were exposed to a range dose of microcystin-RR. Lipid peroxidation, a main manifestation of oxidative damage, was studied and a time- and dose-dependent increase in malondiadehyde was observed. In contrast, glutathione (GSH) levels in the cells decreased after 48 h treatment with 1 and 5 mg/L of microcystin-RR. The activities of superoxide dismutase (SOD) and catalase (CAT) increased significantly after 48 h exposure to 1 and 5 mg/L of microcystin-RR, but glutathione S-transferase (GST) activity showed no difference compared with the control. These results clearly indicate that microcystin-RR is able to cause oxidative damage in A. thaliana suspension cells. Decrease of GSH content and increases of SOD and CAT activities reveal that the antioxidant system may play an important role in eliminating or alleviating the toxicity of microcystin-RR. The possible toxicity mechanism of microcystin-RR on the A. thaliana suspension cells is also discussed in this paper.     

Microcystin-RR-induced accumulation of reactive oxygen species and alteration of antioxidant systems in tobacco BY-2 cells.

Microcystins are cyclic heptapeptide hepatoxins produced by cyanobacteria. It has been shown that microcystins have adverse effects on animals and on plants as well. Previous researches also indicated that microcystins were capable of inducing oxidative damage in animals both in vivo and in vitro. In this study, tobacco BY-2 suspension cell line was applied to examine the effects of microcystin-RR on plant cells. Cell viability and five biochemical parameters including reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPX) and peroxide dismutase (POD) were investigated when cells were exposed to 50mg/L microcystin-RR. Results showed that microcystin-RR evoked decline of the cell viability to approximately 80% after treating for 144 h. ROS levels, POD and GPX activities of the treated cells were gradually increased with a time dependent manner. Changes of SOD and CAT activities were also detected in BY-2 cells. After 168 h recovery, ROS contents, POD, GPX and CAT activities returned to normal levels. These results suggest that the microcystin-RR can cause the increase of ROS contents in plant cells and these changes led to oxidant stress, at the same time, the plant cells would improve their antioxidant abilities to combat mirocystin-RR induced oxidative injury.     

Responses of antioxidant systems in the hepatocytes of common carp (Cyprinus carpio L.) to the toxicity of microcystin-LR.

The freshwater, bloom-forming cyanobacterium (blue-green alga) Microcystis aeruginosa produces a peptide hepatotoxin, which causes the damage of animal liver. Recently, toxic Microcystis blooms frequently occur in the eutrophic Dianchi Lake (300 km2 and located in the South-Western of China). Microcystin-LR from Microcystis in Dianchi was isolated and purified by high performance liquid chromatography (HPLC) and its toxicity to mouse and fish liver was studied (Li et al., 2001). In this study, six biochemical parameters (reactive oxygen species, glutathione, superoxide dismutase, catalase, glutathione peroxide and glutathione S-transferase) were determined in common carp hepatocytes when the cells were exposed to 10 microg microcystin-LR per litre. The results showed that reactive oxygen species (ROS) contents increased by more than one-time compared with the control after 6 h exposure to the toxin. In contrast, glutathione (GSH) levels in the hepatocytes exposed to microcystin-LR decreased by 47% compared with the control. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxide (GSH-Px) increased significantly after 6 h exposure to microcystin-LR, but glutathione S-transferase (GST) activity showed no difference from the control. These results suggested that the toxicity of microcystin-LR caused the increase of ROS contents and the depletion of GSH in hepatocytes exposed to the toxin and these changes led to oxidant shock in hepatocytes. Increases of SOD, CAT and GSH-Px activities revealed that these three kinds of antioxidant enzymes might play important roles in eliminating the excessive ROS. This paper also examined the possible toxicity mechanism of microcystin-LR on the fish hepatocytes and the results were similar to those with mouse hepatocytes.     

Effects of polysaccharide peptides from COV-1 strain of Coriolus versicolor on glutathione and glutathione-related enzymes in the mouse.

The effects of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of PSP (1-4 micromole/kg, i.p.) produced a transient, dose-dependent depletion (10-37%) of hepatic GSH, with no effect on serum glutamic-pyruvic transaminase (SGPT) activity. Blood GSH was depleted (6-25%) at 3 h, followed by a rebound increase above the control GSH level (20%) at 18 h. The GSSG/GSH ratio, a measure of oxidative stress, was increased 3 h after PSP treatment but returned to normal levels at 24 h. Sub-chronic treatment of PSP (1-4 micromole/kg/day, i.p.) for seven days did not produce any significant changes in hepatic GSH levels and the GSSG/GSH ratio when measured 24 h after the final dose of PSP. PSP had little effect on glutathione transferase (GST), glutathione reductase (GSSG reductase) and glutathione peroxidase (GPX) activities in the liver. However, a dose-dependent increase in blood GPX activity (30-48%) was observed at 3h, which coincided with the increase in the GSSG/GSH ratio. The increase in blood GPX activity may be a responsive measure to deal with the transient oxidative stress induced by PSP treatment. The results showed that PSP only caused a transient perturbation on hepatic glutathione without affecting the GSH-related enzymes such as GST, GSSG reductase and GPX. The observed changes in blood GSH simply reflected the intra-organ translocation of glutathione, as the glutathione-related enzymes were not significantly affected by PSP treatment.     

The effects of bucillamine on glutathione and glutathione-related enzymes in the mouse

The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied previously. GSH depletion after acute BA administration correlated well with the elevation of serum glutamic-pyruvic transaminase (SGPT) (6-9-fold increase above control). The increase in SGPT after chronic administration (7 days), although significantly higher than the controls, was however much less than after acute administration. The hepatic GSH concentrations of mice given 7 days of BA were similar to the controls, again correlating well with SGPT activity. Administration of BA (150-400 mg/kg) caused also a significant dose-dependent increase in the oxidized glutathione (GSSG) in blood by 2-7-fold, as well as a dose-dependent increase in blood glutathione S-transferase (GST) activity (2-13-fold). In an in vitro experiment, hepatic GST activity was activated by various concentrations of BA (1 microM-1mM). There was little or no effect on GSSG reductase and on glutathione peroxidase (GSH-Px) after acute administration of BA. Chronic administration of BA had no effect on hepatic GSSG reductase and GSH-Px, but GSSG reductase activity in blood was increased significantly by 4-fold. It is possible that BA may affect the redox status through auto-oxidation and oxidation with endogenous thiols such as glutathione, affecting GSH concentrations and the GSH/GSSG ratio in tissues and, thus, having both metabolic and toxicological consequences. Whether or not the induction of GST activity in vivo in blood and in vitro in liver enzyme preparations shared the same underlying mechanism(s) requires further investigation.     

The interplay of glutathione-related processes in antioxidant defense

This review summarizes current knowledge on glutathione (GSH) associated cellular processes that play a central role in defense against oxidative stress. GSH itself is a critical factor in maintaining the cellular redox balance and has been demonstrated to be involved in regulation of cell signalling and repair pathways. Enhanced expression of various enzymes involved in GSH metabolism, including glutathione peroxidases, γ-glutamyl cysteinyl synthetase (γ-GCS), glutathione S-transferases (GST) and membrane proteins belonging to the ATP-binding cassette family, such as the multidrug resistance associated protein, have all been demonstrated to play a prominent role in cellular resistance towards oxidative stress. This review stresses the fact that a co-ordinate interplay between these systems is essential for efficient protection against oxidative stress.     

Effect of exercise training on antioxidant system in brain regions of rat

The purpose of this investigation was to determine whether any alterations in antioxidant enzyme activities and levels of glutathione (GSH) in brain regions occurred following exercise training. Sprague-Dawley rats were given exercise training on a treadmill for 7.5 weeks and sacrificed 18 h after the last exercise along with the sedentary control rats. Different brain regions—cerebral cortex (CC), brainstem (BS), corpus striatum (CS), and hippocampus (H)—were isolated; GSH, oxidized glutathione (GSSG), Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined. The exercise training increased SOD activity significantly (130% of sedentary control) in BS and in CS. SOD activity in H was the lowest of all four brain regions. Different brain regions showed GSH-Px activity in decreasing order for CS < BS < CC < H. GSH levels were 43% less in BS than CC and CS. The ratio of GSH/ GSSG significantly increased from 6.8 to 8.3 in CC, and from 9.4 to 13.5 in BS as a result of exercise training. Different brain regions contained different activities of antioxidant enzymes, as well as GSH and GSSG levels, which were preferentially altered as a result of exercise training to cope with oxidative stress.     

Folic acid supplementation affects ROS scavenging enzymes, enhances Vegf-A, and diminishes apoptotic state in yolk sacs of embryos of diabetic rats

We aimed to investigate the extent to which maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes, vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis-associated proteins in the yolk sacs of rat embryos on gestational days 10 and 11. Commencing at conception and throughout pregnancy, half of the streptozotocin-diabetic and half of the control rats received daily FA injections. Maternal diabetes impaired vascular morphology and decreased CuZnSOD and GPX-1 gene expression in yolk sacs. Maternal diabetes also increased the levels of CuZnSOD protein, increased the Bax/Bcl-2 protein ratio and decreased Vegf-A protein distribution. FA treatment normalized vascular morphology, decreased mRNA levels of all three SOD isoforms and increased Vegf-A mRNA levels, rectified CuZnSOD protein distribution and Bax/Bcl-2 ratio. A teratogenic diabetic environment produces a state of vasculopathy, oxidative stress, and mild apoptosis in the yolk sac. FA administration normalizes vascular morphology, diminishes apoptotic rate, and increases Vegf-A gene expression and protein distribution in the yolk sac of diabetic rats.     

Glutathione consumption and inactivation of glutathione-related enzymes in liver, erythrocytes and serum of rats after methanol intoxication

The primary metabolic fate of methanol is oxidation to formaldehyde and then to formate. These processes are accompanied by formation of superoxide anion and further hydrogen peroxide. Glutathione plays a unique role in the cellular defence system against xenobiotics. The glutathione (GSH) content and glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-R) activities were measured in liver, erythrocytes and serum of rats. Rats were intoxicated with 3.0 and 6.0 g methanol/kg body wt. and measurements taken after 6, 12 and 24 h and 2, 5 and 7 days of intoxication. The decrease in GSH content and in GSH-related enzyme activity was observed during the whole time-course of the intoxication. The most significant changes were observed in the erythrocytes. The results obtained show that the protection against oxidative damage due to methanol intoxication in rats seems to be less efficient than in control rats. Received: 7 January 1997 / Accepted: 26 May 1997     

EFFECT OF TUMOR NECROSIS FACTOR ON HEPATIC OXIDATIVE STRESS AND ANTIOXIDANT DEFENSE INDICES IN NORMAL AND PLASMODIUM YEOLII NIGERIENSIS INFECTED MICE

Background: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide along with endogenously produced tumor necrosis factor (TNF) have been implicated in the pathogenesis of malaria. Objective: Study the effect of TNF on hepatic oxidative stress and antioxidant defense indices in normal and P. y. nigeriensis infected mice. Methods: Mice were divided into four groups. Normal group, TNF treated group, P. y. nigeriensis infected group, and P. y. nigeriensis infected mice treated with TNF group (250 μg/kg body weight, IP). Results: TNF treatment of normal mice caused a highly significant decrease in hepatic superoxide dismutase (SOD) while changes in other oxidative stress and antioxidant defense indices were nonsignificant. On the other hand, TNF treatment of P. y. nigeriensis infected mice caused a highly significant increase in hepatic xanthine oxidase, lipid peroxidation and a significant decrease in hepatic SOD with respect to infected mice. Conclusion: These results suggest that exogenous TNF acts synergistically with P. y. nigeriensis infection to generate oxidative stress in the host and also causes an impairment of antioxidant defense enzyme such as superoxide dismutase.     

Dose-response relationship of cadmium embryotoxicity in cultured mouse embryos

Mouse embryos were exposed in vitro to 1.2 to 2.2 μM cadmium, and effects on embryotoxicity were examined after 39 h of culture. Teratogenic responses similar to in vivo were obtained at 1.2 to 2.2 μM with concomitant reduction in embryonic protein, while embryo deaths were increased from 13.8 to 93.3% at 2.0 to 2.2 μM. The response data of both teratogenicity and growth parameters, including embryonic protein, head lenght, crown-rump lenght, somite number, and protein and diameter of yolk sac, were acceptably fitted to a cadmium is a critical parameter in the manifestation of teratogenic potential, (b) as an estimation of interference in the growth of embryos, embryonic protein is one of the most sensitive endpoints while somite number is an insensitive criterion, and (c) a linear log-probit regression is applicable to the analyses of embryotoxicity data, including growth parameters in whole-embryo culture systems.     

Sex differences in the cellular defence system against free radicals from oxygen or drug metabolites in rat

In this study, it was investigated whether sex-related differences in the protective mechanisms against oxygen radicals and free radical metabolites from drugs were present in rat liver, heart, and kidney. To that end, superoxide dismutase, catalase, the factors of the glutathione system and vitamin E were measured. In addition, NADPH-dependent cytochrome c-reductase activity was established, as this enzyme is involved in the formation of free radicals in the presence of many xenobiotics. The total capacity of the cellular systems that detoxify reactive oxygen species or free radical-drug metabolites seems to be higher in female liver as compared to male. No differences were found for heart and kidney tissue. It is hypothesized that female rats probably are less vulnerable for those drugs whose hepatotoxic action is induced by excessive formation of free radical species.     

急性运动所致氧化应激及谷氨酰胺的保护作用

目的探讨补充外源性谷氨酰胺(Gln)对急性运动应激大鼠的抗氧化保护作用。方法采用大鼠力竭性游泳方式,通过补充Gln对比实验,于力竭游泳后2小时,观察大鼠血清、股四头肌和心肌组织中谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量的变化。结果力竭性游泳大鼠骨骼肌MDA显著升高;血清、骨骼肌SOD显著升高,心肌SOD显著下降;血清GSH显著下降。补充Gln能抑制力竭游泳后大鼠骨骼肌MDA升高;抑制血清、骨骼肌SOD升高和心肌SOD下降。结论Gln对急性运动所致的氧化应激有一定的保护作用。