抗氧化剂在糖尿病中的应用研究进展

氧化应激是自由基的促氧化与机体的抗氧化失衡造成的.自由基的高反应活性可以使细胞组分发生化学变化,并导致脂质过氧化.越来越多的证据表明:糖尿病患者体内活性氧物质明显增多,并且抗氧化防御系统功能紊乱.抗氧化剂可以降低糖尿病患者体内的氧化应激水平,清除自由基并改善抗氧化防御体系,所以将抗氧化剂应用于糖尿病是可行的.许多抗氧化剂已经用于糖尿病的研究与治疗,本文主要将作用于糖尿病的各种抗氧化剂做一综述.     

Role of antioxidants in protecting cellular DNA from damage by oxidative stress

We have previously derived 2 V79 clones resistant to menadione (Md1 cells) and cadmium (Cd1 cells), respectively. They both were shown to be cross-resistant to hydrogen peroxide. There was a modification in the antioxidant repertoire in these cells as compared to the parental cells. Md1 presented an increase in catalase and glutathione peroxidase activities whereas Cd1 cells exhibited an increase in metallothionein and glutathione contents. The susceptibility of the DNA of these cells to the damaging effect of H₂O₂ was tested using the DNA precipitation assay. Both Md1 and Cd1 DNAs were more resistant to the peroxide action. In the case of Md1 cells it seems clear that the extra resistance is provided by the increase in the two H₂O₂ scavenger enzymes, catalase and glutathione peroxidase. In the case of Cd1 cells the activities of these enzymes as well as of superoxide dismutases (Cu/Zn and Mn) are unaltered as compared to the parental cells. The facts that parental cells exposed to 100 μM Zn²⁺ in the medium exhibit an increase in metallothionein but not in glutathione and that these cells become more resistant to the DNA-damaging effect of H₂O₂ suggest that this protein might play a protective role in vivo against the OH radical attack on DNA.     

臭氧自血疗法及其在糖尿病治疗中的应用

目前,糖尿病及其并发症已经成为我国一个重大的公共卫生问题。大量研究证实,氧化应激与糖尿病大血管和微血管并发症的发生及发展密切相关。臭氧自血疗法的应用已有半个世纪,低强度、精确计算且可重复的臭氧自血治疗可诱发标准化的急性氧化应激,使机体的抗氧化防御系统得到锻炼和增强,而在此过程中产生的一定数量的信使,可以与血液和实质细胞产生相互作用,改善缺血组织的血液循环和氧供,使免疫系统轻度活化,增加生长因子的释放,激活神经保护系统,改善患者的健康状态。虽然有证据显示臭氧治疗在改善血糖和血脂控制方面的贡献,且安全性良好,但迄今为止,臭氧自血疗法的临床试验数据还相当欠缺,有必要开展设计良好的临床试验,进行长期观察,以获得其应用和推广所需的更为确凿的证据。本综述旨在探讨臭氧自血疗法的作用机制及应用前景。     

A comparison of mechanisms of desiccation tolerance among three angiosperm resurrection plant species

The mechanisms of protection against mechanical and oxidative stress were identified and compared in the angiosperm resurrection plants Craterostigma wilmsii, Myrothamnus flabellifolius and Xerophyta humilis. Drying-induced ultrastructural changes within mesophyll cells were followed to gain an understanding of the mechanisms of mechanical stabilisation. In all three species, water filled vacuoles present in hydrated cells were replaced by several smaller vacuoles filled with non-aqueous substances. In X. humilis, these occupied a large proportion of the cytoplasm, preventing plasmalemma withdrawal and cell wall collapse. In C. wilmsii, vacuoles were small but extensive cell wall folding occurred to prevent plasmalemma withdrawal. In M. flabellifolius, some degree of vacuolation and wall folding occurred, but neither were sufficient to prevent plasmalemma withdrawal. This membrane was not ruptured, possibly due to membrane repair at plasmodesmata junctions where tearing might have occurred. In addition, the extra-cytoplasmic compartment appeared to contain material (possibly similar to that in vacuoles) which could facilitate stabilisation of dry cells.Photosynthesis and respiration are particularly susceptible to oxidative stress during drying. Photosynthesis ceased at high water contents and it is proposed that a controlled shut down of this metabolism occurred in order to minimise the potential for photo-oxidation. The mechanisms whereby this was achieved varied among the species. In X. humilis, chlorophyll was degraded and thylakoid membranes dismantled during drying. In both C. wilmsii and M. flabellifolius, chlorophyll was retained, but photosynthesis was stopped due to chlorophyll shading from leaf folding and anthocyanin accumulation. Furthermore, in M. flabellifolius thylakoid membranes became unstacked during drying. All species continued respiration during drying to 10% relative water content, which is proposed to be necessary for energy to establish protection mechanisms. Activity of antioxidant enzymes increased during drying and remained high at low water contents in all species, ameliorating free radical damage from both photosynthesis and respiration. The nature and extent of antioxidant upregulation varied among the species. In C. wilmsii, only ascorbate peroxidise activity increased, but in M. flabellifolius and X. humilis ascorbate peroxidise, glutathione reductase and superoxide dismutase activity increased, to various extents, during drying. Anthocyanins accumulated in all species but this was more extensive in the homoiochlorophyllous types, possibly for protection against photo-oxidation.     

Effect of 900 MHz radiofrequency radiation on oxidative stress in rat brain and serum

The increasing use of mobile telephones raises the question of possible adverse effects of the electromagnetic fields (EMF) that these phones produce. In this study, we examined the oxidative stress in the brain tissue and serum of rats that resulted from exposure to a 900-MHz EMF at a whole body average specific absorption rate (SAR) of 1.08 W/kg for 1 h/day for 3 weeks. We also examined the antioxidant effect of garlic powder (500 mg/kg/day) given orally to EMF-exposed rats. We found that malondialdehyde (MDA) (p < 0.001) and advanced oxidation protein product (AOPP) (p < 0.05) increased in rat brain tissue exposed to the EMF and that garlic reduced these effects (p < 0.05). There was no significant difference in the nitric oxide (NO) levels in the brain. Paraoxonase (PON) was not detected in the brain. There was a significant increase in the levels of NO (p < 0.001) detected in the serum after EMF exposure, and garlic intake did not affect this increase in NO. Our results suggest that there is a significant increase in brain lipid and protein oxidation after electromagnetic radiation (EMR) exposure and that garlic has a protective effect against this oxidative stress.     

Oxidative Stress in Cerebrospinal Fluid of Patients with Aseptic and Bacterial Meningitis

This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS) and antioxidant defense systems such as superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and ascorbic acid. TBARS levels, SOD and GST activity increase in aseptic meningitis and in bacterial meningitis. The ascorbic acid concentration increased significantly in patients with both meningitis types. The reduced glutathione levels were reduced in CSF of patients with aseptic and bacterial meningitis. In present study we may conclude that oxidative stress contributes at least in part to the severe neurological dysfunction found in meningitis.     

Antioxidant Status in the Blood of Patients With Active Vitiligo

We have previously reported that patients with active vitiligo (AVP) have elevated urinary levels of catecholamine metabolites, such as homovanillic and vanilmandelic acids, irrespective of the form of the disease (acrofacial, segmental, generalized). We have suggested that abnormal release of catecholamines from autonomic nerve endings might play an etiological role in the onset and development of vitiligo through an overproduction of toxic (oxy)radicals in the microenvironment of melanocytes in the affected areas. In the present study we have investigated whether this suggested increase in radicals might be associated with an oxidative stress in the blood of AVP. We have analyzed by gas-chromatography mass-spectrometry, by high pressure liquid chromatography, by spectophotometry plasma levels of vitamin E (Vit E), lipoperoxides (LIP), and polyunsaturated fatty acids of phospholipids (PL-FA), erythrocyte reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in 62 patients affected with different forms of active vitiligo (acrofacial, segmental, generalized) and in 60 age-matched controls. Our results show that blood levels of Vit E, SOD, GSH, GSH-Px activity, LIP and PL-FA in AVP were not significantly different from those of healthy age matched controls, indicating that melanocyte damage in vitiligo is not linked with a generalized oxidative stress.     

Cloning of the ferrireductase that may be involved in iron transport in the small intestine: revisiting Crane's controversial oxidoreductase

Abstract

Objectives

Oxidative stress and inflammation have been reported to be higher in subjects with depression, but it is unclear whether this is due to inadequate dietary antioxidant intake or the pathophysiology of depression. The aim of this study was to assess the association between dietary and serum antioxidant status with depression scales in young male university students.

Methods

This research was a case–control study carried out on 60 male university students (30 students diagnosed with depression and 30 matched healthy controls). Beck Depression Inventory-II was used to assess the major depressive disorder (MDD) scales. A semi-quantitative food frequency questionnaire and 2-day 24-h recalls were used for dietary assessment. Dietary and serum total antioxidant capacity (TAC) and high-sensitive C-reactive protein (hs-CRP) concentrations were also measured.

Results

MDD subjects consumed less fruits (P < 0.05), legumes (P < 0.001), nuts and seeds (P = 0.003), vitamin C (P = 0.005), beta carotene (P < 0.001), lutein, and zeaxanthin (P = 0.006) than the controls. Moreover, the depressed group had lower serum TAC levels than their controls (P < 0.05). There were no significant differences in serum hs-CRP concentrations and dietary TAC levels between the study groups.

Discussion

Students with depression had significantly lower intake of dietary antioxidants. However, dietary TAC and serum hs-CRP levels were not significantly different between depressed and normal university male students. Intake of foods rich in antioxidants is encouraged in male students.     

Quantitative structure-activity relationships in prooxidant cytotoxicity of polyphenols: role of potential of phenoxyl radical/phenol redox couple

The aim of this work was to characterize the role of the potential of phenoxyl radical/phenol redox couple, E(7)(2), in the cytotoxicity of polyphenols. The cytotoxicity of polyphenols in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK), and human promyelocytic leukemia cells (line HL-60) was partly inhibited by catalase, by the antioxidant N,N'-diphenyl-p-phenylene diamine and desferrioxamine, and potentiated by 1,3-bis-(2-chloro-ethyl)-1-nitrosourea, thus showing its prooxidant character. Dapsone, an inhibitor of myeloperoxidase, did not affect the cytotoxicity of polyphenols in HL-60 cells, whereas dicumarol, an inhibitor of DT-diaphorase, showed controversial effects on their cytotoxicity in FLK cells. Inhibitors of cytochromes P-450, alpha-naphthoflavone and izoniazide, decreased the cytotoxicity of several polyphenols, whereas 3,5-dinitrocatechol, an inhibitor of catechol-o-methyltransferase (COMT), increased it. The cytotoxicity of 13 polyhydroxybenzenes was described by the equations: logcL50 (microM) = -0.67 + 5.46E(7)(2) (V) - 0.16 logD (FLK), and logcL50 (microM) = -1.39 + 6.90E(7)(2) (V) - 0.20logD (HL-60), where cL50 is compound concentration for 50% cell survival, and D is octanol/water distribution coefficient at pH 7.0. The flavonoids comprise a separate series of compounds with lower cytotoxicity. The correlations obtained quantitatively confirm the parallelism between the polyphenol cytotoxicity and the rates of their single-electron oxidation, and point to the leading role of formation of the reactive oxygen species in their cytotoxicity. Depending on the examined system, this parallelism may be distorted due to the cytochrome P-450 and COMT-catalyzed transformation of polyphenols.     

The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis

Abstract

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the most common underlying causes of chronic liver injury. They are associated with a wide spectrum of hepatic disorders including basic steatosis, steatohepatitis, and cirrhosis. The molecular and cellular mechanisms underlying hepatic injury in NAFLD and NASH are still unknown. This review describes the roles of oxidative stress and inflammatory responses in the pathogenesis of NAFLD and its progression to NASH.     

Effects of α lipoic acid on noise induced oxidative stress in rats

This study was conducted to identify how exposure to ambient noise that is over 75 dB affects the oxidant-antioxidant profile using hematological and biochemical indicators, and to investigate the effects of a strong and current antioxidant, $\alpha$ lipoic acid, on rats that were subjected to noise stress. For this purpose, five groups of eight rats were formed as follows: Control (K), Noise Exposure (GK), Lipoic Acid (LA), Noise Pollution + $\alpha$Lipoic Acid (GK + LA) and Oil (Y). The blood samples collected from rats were analyzed and MDA (malondialdehyde), GSH (glutathione), SOD (superoxide dismutase), CAT (catalase), NO (nitrit oxide), GPx (glutathione peroxidase), leukocytes, monocytes, lymphocytes, erythrocytes, hemoglobin, hematocrit, glucose, cholesterol, total protein, triglycerides, HDL (high density lipoprotein), LDL (low density lipoprotein), and urea-N levels were measured. The physical factory environment in a textile factory was preferred to simulate the noise exposure. Ambient noise was measured to be 75 dB. Exposure to physical ambient noise was sustained for 30 days. MDA level was measured at the lowest level in the LA and GKLA groups while it was statistically significantly higher in other groups than it was in the control group. It was observed that GSH reached its lowest level in the group that was exposed to noisy environment, the 100 mg/kg/day $\alpha$lipoic acid administered on the experimental model increased this level to that of the control group and this change was statistically significant (p < 0.05). Considering the urea levels, the increases in GK and GKLA groups and the decreases in LA and Y groups were observed to be statistically significant. When glucose levels were compared to the control group, they were found to be statistically significantly lower in all groups. As a result, it was observed that exposure to noise for 30 days was likely to lead to leukocyte-based immune deficiency and using $\alpha$ lipoic acid as an antioxidant might provide a significant protection against the noise stress.     

Effects of green tea and physical exercise on memory impairments associated with aging

We investigated the effects of physical exercise and green tea supplementation (associated or not) on biochemical and behavioral parameters in the time course of normal aging. Male Wistar rats aged 9 months were divided into groups: control, physical exercise (treadmill running), and supplemented with green tea while either performing physical exercise or not. A young control group was also studied. Physical exercise and green tea supplementation lasted 3 months. Afterwards, behavioral and biochemical tests were performed. Biochemical measurements revealed differences in antioxidant and oxidant responses in hippocampus, prefrontal cortex and striatum. Behavioral testing showed age-related memory impairments reversed by physical exercise. The association of green tea supplementation and physical exercise did not provide aged rats with additional improvements in memory or brain oxidative markers. Green tea per se significantly decreased reactive oxygen species levels and improved antioxidant defenses although it did not reverse memory deficits associated with normal aging.     

The influence of the duration of the expulsive stage of parturition on the occurrence of postpartum oxidative stress in sows with uncomplicated,spontaneous farrowings

The aim of the study was to determine the influence of the duration of the expulsive stage of parturition on the occurrence of postpartum oxidative stress in sows with uncomplicated, spontaneous farrowings. Twenty-five pregnant gilts were divided into three groups on the basis of duration of the expulsive stage of farrowing: (I) duration of the expulsive stage was below 3 hours; (II) duration of the expulsive stage ranged from 3 to 6 hours; (III) duration of the expulsive stage was longer than 6 hours. Blood samples were collected at 24 to 48 hours before and 24 hours after parturition. As indicators of alterations in the redox state, we quantified the enzymatic activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), as well as the blood levels of glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and sulfhydryl groups (SH groups). In group III, it was found that erythrocyte activity of CAT (63.89 ± 6.70 vs. 53.18 ± 2.32 U/g Hb), as well as plasma GSH concentration (0.088 ± 0.020 vs. 0.045 ± 0.024 mmol/g protein) and SH groups content (5.045 ± 1.256 vs. 3.383 ± 0.430 μmol/g protein) decreased significantly (P < 0.05) at 24 hours after parturition, compared with their values during the last 48 hours before parturition. The concentration of TBARS increased not significantly, although markedly at 24 hours postpartum in group III (0.124 ± 0.014 vs. 0.153 ± 0.031 μmol/g protein). The results indicate that uncomplicated, spontaneous parturition can lead to the occurrence of oxidative stress during the early postparturient period in sows, the intensity of which is related to the duration of the expulsive stage.     

Zinc deficiency differentially affects redox homeostasis of rice genotypes contrasting in ascorbate level

Zinc (Zn) deficiency is an important mineral disorder affecting rice production, and is associated with the formation of oxidative stress in plant tissue. In this study we investigated processes of oxidative stress formation as affected by ascorbate (AsA) in two pairs of contrasting rice genotypes: (i) two indica lines differing in field tolerance to Zn deficiency and AsA metabolism, i.e. RIL46 (tolerant) and IR74 (sensitive); (ii) the japonica wild-type Nipponbare (tolerant) and the AsA deficient TOS17 mutant line ND6172 (sensitive) having a 20–30% lower AsA level due to the knockout of an AsA biosynthetic gene (OsGME1). Plants were grown hydroponically under +Zn and −Zn conditions for 21 days and samples were investigated after 7, 14, and 21 days of treatment. Tissue Zn concentrations below 20 mg kg⁻¹ in the −Zn treatment induced the formation of visible symptoms of Zn deficiency from day 14 in all genotypes, but especially in the sensitive IR74. Significant increases in lipid peroxidation were observed in the leaves of the sensitive genotypes IR74 and ND6172, and in the roots of IR74, but not in the tolerant genotypes. At day 21, the tolerant genotypes RIL46 and Nipponbare had significantly higher AsA levels in both shoots and roots compared to the sensitive lines. Consistently, higher levels of hydrogen peroxide formation in leaves and roots of the sensitive genotypes were detected using staining methods. Differences in foliar hydrogen peroxide formation between IR74 and RIL46 became apparent on day 7 and between ND6172 and Nipponbare on day 14. Similarly, genotypic differences in hydrogen peroxide formation in the roots were seen on day 21. In conclusion, our data demonstrate that Zn deficiency leads to a redox imbalance in roots and shoots prior to the occurrence of visible symptoms, and that the antioxidant AsA plays an important role in maintaining the redox homeostasis under Zn deficiency.     

Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats

Nickel (Ni), a major environmental pollutant, is known for its wide toxic manifestations. In the present study caffeic acid (CA), one of the most commonly occurring phenolic acids in fruits, grains and dietary supplements, was evaluated for its protective effect against the Ni induced oxidative damage in liver. In this investigation, Ni (20 mg/kg body weight) was administered intraperitoneally for 20 days to induce toxicity. CA was administered orally (15, 30 and 60 mg/kg body weight) for 20 days with intraperitoneal administration of Ni. Ni induced liver damage was clearly shown by the increased activities of serum hepatic enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) along with increased elevation of lipid peroxidation indices (thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides). The toxic effect of Ni was also indicated by significantly decreased levels of enzymatic (superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (glutathione (GSH), vitamin C and vitamin E). CA administered at a dose of 60 mg/kg body weight significantly reversed the activities of hepatic marker enzymes to their near normal levels when compared with other two doses. In addition, CA significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. All these changes were supported by histological observations. The results indicate that CA may be beneficial in ameliorating the Ni induced oxidative damage in the liver of rats.