Vitamin E and selenium administration as a modulator of antioxidant defense system: biochemical assessment and modification

Exposure of cells to ionizing radiation leads to the formation of reactive oxygen species (ROS) that are associated with radiation-induced cytotoxicity. Because of the serious damaging potential of ROS, cells depend on the elaboration of the antioxidant defense system (AODS), both enzymatic and nonenzymatic oxidant defense mechanisms. The deficiency in important components of the endogenous AODS leads to the accumulation of oxidative stress inducing oxidative damage. The antioxidant enzymes superoxide dismutase and glutathione peroxidase are key intracellular antioxidants in the metabolism of ROS. In the current study, we investigated the potential role of these antioxidant enzymes in radioresistance during the evaluation of the compensatory role of some exogenous micronutrients against oxidative stress Animals were categorized into eight groups, receiving vitamin E (α-tocopherol) and/or selenium (Se) with or without whole-body γ-irradiation (6.5 Gy). The results indicate that antioxidant pretreatments before irradiation may have some beneficial effects against irradiation-induced injury. The results also indicate that selenium and vitamin E act alone and in an additive fashion as radioprotecting agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown, whereas vitamin E appears to confer its protection by an alternate complementary mechanism.     

Autoimmunity as a special case of immunity: removing threats from within

The function of the adaptive immune response against exogenous (non-self) agents is to help the innate arm of the immune system (represented by phagocytic cells) to fight and eliminate these agents. We suggest that the body also protects itself against potentially harmful self components using mechanisms similar to those used for fighting and eliminating non-self agents, and that the protective immune activity against self-components competes with the activity of self-destructive compounds. Tolerance to self is thus not a lack of response to self, but the ability to tolerate an active defense response to self without developing an autoimmune disease.     

C60 carboxyfullerene exerts a protective activity against oxidative stress-induced apoptosis in human peripheral blood mononuclear cells

C60 carboxyfullerene is a novel buckminsterfullerene-derived compound that behaves as a free-radical scavenger. In the present report, we investigated whether this drug exerts a protective activity against oxidative stress-induced apoptosis. Human peripheral blood mononuclear cells (PBMCs) were challenged by 2-deoxy-d-ribose (dRib) or TNF-alpha plus cycloheximide as agents that trigger apoptosis by interfering with the redox status of cell and mitochondrial membrane potential. We found that carboxyfullerene was able to protect quiescent PBMCs from apoptosis caused either by 2-deoxy-d-ribose or TNF-alpha plus cycloheximide by a mechanism partially involving the mitochondrial membrane potential integrity, known to be associated with early stages of apoptosis. These results represent the first indication for a target activity of buckminsterfullerenes on cells of the immune system and their mitochondria.     

Aldehyde dehydrogenase, aldose reductase, and free radical scavengers in cataract

Human lens was found to contain aldehyde dehydrogenase at a level of activity similar to that of bovine lens, namely 1.76 +/- 0.51 IU/g. The enzyme, which appears to be a tetramer of 229 kD, was less susceptible to inhibition by cataractogenic agents than the bovine enzyme. The lipid peroxidation product malondialdehyde was a good substrate of the human lens enzyme. The in vitro aldose reductase reaction, which we have shown is caused by glyceraldehyde-stimulated free-radical NADPH oxidation, is inhibited by the potential anti-cataract agents, bendazac acid and bendazac lysine; these compounds also inhibit ferricytochrome c reduction in the presence of DL-glyceraldehyde and scavenge superoxide radicals. These results are consistent with the hypotheses that aldehyde dehydrogenase is a protective enzyme in the human lens, and that the peroxy radical scavenging effects of bendazac acid and bendazac lysine contribute to their anti-cataract activity.     

Antioxidant activity and protective effect on DNA cleavage of extracts from Cistus incanus L. and Cistus monspeliensis L.

The genus Cistus includes many typical species of Mediterranean flora; Cistus species are used as antidiarrheics, as general remedies for treatment of various skin diseases in folk medicine and as anti-inflammatory agents. These species contain flavonoids that are considered to be chain-breaking antioxidants. In this work, we have investigated the effects of crude aqueous extracts from Cistus incanus and Cistus monspeliensis on DNA cleavage and their free-radical scavenging capacity. In addition, their effect on lipid peroxidation in rat liver microsomes was evaluated. These extracts showed a protective effect on DNA cleavage and a dose-dependent free-radical scavenging capacity; Cistus monspeliensis was more active than Cistus incanus; these results were confirmed by a significant inhibition of lipid peroxidation in rat liver microsomes. The experimental evidence, therefore, suggests that because of their antioxidant activity these extracts may offer excellent photoprotection for skin and may be useful in the treatment of human diseases where oxidative stress plays a key role. This revised version was published online in July 2006 with corrections to the Cover Date.     

The role of free radical processes and redox-signalization in adaptation of the organism to changes in oxygen level

Data are presented on participation of free-radical oxygenation in development of the organism adaptation. The redox-signalization concept is discussed in the aspect of its responsibility for the initial stage of external signal transmission to the cell genetic apparatus. The pro- and antioxidant system ratio is noted as important for assessment of formation of the cell structure and the tissue resistance. A protective effect of periodic hyperoxia was shown as well as regularities of its development similar formation of adaptation to the periodic hyperoxia.     

植物组织培养外植体褐变的研究进展

外植体的褐变是组织培养过程中的主要障碍。目前一般认为影响褐变的因素主要有外植体材料、培养基和培养条件。为了防止褐变的发生,主要可以从外植体和培养条件、进行细胞筛选和材料的预处理、抑制剂或吸附剂的加入等方面入手。酚、酚酶的区域性分布假说、自由基伤害假说、保护酶系统假说是褐变机理方面较为成熟的3种假说。     

Chemesthesis and the chemical senses as components of a "chemofensor complex"

An important function of the chemical senses is to warn against dangerous biological and chemical agents in the environment. The discovery in recent years of "taste" receptor cells outside the oral cavity that appear to have protective functions has raised new questions about the nature and scope of the chemical senses in general and of chemesthesis in particular. The present paper briefly reviews these findings within the context of what is currently known about the body's chemically sensitive protective mechanisms, including nonsensory processes that help to expel or neutralize threatening agents once they have been encountered. It is proposed that this array of defense mechanisms constitutes a "chemofensor complex" in which chemesthesis is the most ubiquitous, functionally diverse, and interactive chemosensory component.     

Synergistic effect of Nicorandil and Amlodipine on tissue defense system during experimental myocardial infarction in rats

The synergistic protective effect of Nicorandil (K_ATP channel opener) and Amlodipine (calcium channel blocker) on heart tissue antioxidant defense system and lipid profile were examined on isoproterenol induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg^–1 daily, i.p.) for 2 days showed significant changes in antioxidant defense system and lipid profile levels. Pretreatment with Nicorandil (2.5 mg kg^–1 daily, p.o.) and Amlodipine (5.0 mg kg^–1 daily, p.o.) for 3 days significantly prevented these alterations and restored the enzyme activities to near normal. These findings indicate the synergistic protective effect of Nicorandil and Amlodipine on tissue defense system and lipid metabolism during isoproterenol induced cardiac damage.     

Assay of free-radical toxicity and antioxidant effect on the Hep 3B cell line: a test survey using lindane

The content of reduced glutathione and of glutathione disulfide as well as the activities of glutathione reductase, glutathione peroxidase, glutathione S-transferases, catalase and superoxide dismutases were determined in human hepatoma Hep 3B cells in relation to free-radical toxicity in order to appreciate the defense capacities of these cells compared to data on normal hepatocytes. When Hep 3B cells were exposed to lindane, a known inducer of free-radical production, superoxide dismutase activity appeared as the best-adapted cellular parameter for early detection of the resulting free-radical toxicity.Abbreviations AAS atomic absorption spectrometry - CDNB 1-chloro-2,4-dinitrobenzene - DMEM Dulbecco's modified Eagle medium - GPx glutathione peroxidase - G.Red glutathione reductase - GSH reduced glutathione - GSSG glutathione disulfide - GST glutathione S-transferases - Prot proteins - SOD superoxide dismutase     

Immunoprophylaxis in fish by injection of mouse antibody genes

Antibodies are a crucial part of the body's specific defense against infectious diseases and have considerable potential as therapeutic and prophylactic agents in humans and animals. The development of recombinant single-chain antibodies allows a genetic application strategy for prevention of infectious diseases. To test this in a fish model, a gene construct encoding a neutralizing single-chain antibody to the fish-pathogenic rhabdovirus VHSV (viral hemorrhagic septicemia virus) was administered to rainbow trout by intramuscular injection of plasmid DNA. Circulating recombinant antibodies could later be detected in the fish, and protective immunity to the viral disease was established.     

Bioflavonoids as antiradicals,antioxidants and DNA cleavage protectors

Flavonoids have recently aroused considerable interest because of their broad pharmacological activity. In fact, flavonoids have been reported to have antiviral, antiallergic, antiplatelet, anti-inflammatory and antitumoral activities. The pharmacological properties of bioflavonoids have been ascribed both to the concomitant inhibition of enzymes involved in the production of free radicals and to their free-radical scavenging and iron chelating capacity. However the antioxidant capacity of bioflavonoids due to free-radical scavenging and/or to iron chelating is still controversial. In this study, we have investigated the free-radical scavenging capacity of bioflavonoids (rutin, catechin, and naringin). In addition, the effects of these polyphenols on xanthine oxidase activity, spontaneous lipid peroxidation, and DNA cleavage were investigated. The bioflavonoids under examination showed a dose-dependent free-radical scavenging effect, a significant inhibition of xanthine oxidase activity, and an antilipoperoxidative capacity. In addition, they showed a protective effect on DNA cleavage. This revised version was published online in July 2006 with corrections to the Cover Date.     

Protective influence of vitamin E on antioxidant defense system in the blood of rats treated with cadmium

The effects of acute exposure to cadmium (Cd) on the blood antioxidant defense system, lipid peroxide concentration and hematological parameters, as well as the possible protective role of vitamin E were studied. Male Wistar albino rats (3 months old) were treated with cadmium (0.4 mg Cd/kg b.m., i.p., 24 h before the experiment) or with vitamin E + Cd (20 IU Vit E/kg b.m., i.m., 48 h + 0.4 mg Cd/kg b.m., i.p., 24 h before the experiment). The hematological parameters were assessed: red blood cell counts, hematocrit value and hemoglobin concentration were significantly decreased in the blood of Cd-treated rats. Intoxication with cadmium was also followed by significantly increased lipid peroxide concentrations. We also observed increased activity of antioxidant defense enzymes: copper zinc containing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase as well as concentrations of non-enzymatic components of antioxidant defense system: reduced glutathione, vitamin C and vitamin E. Pretreatment with vitamin E exhibited a protective role on the toxic effects of cadmium on the hematological values, lipid peroxide concentration as well as on enzymatic and non-enzymatic components of antioxidant defense system.     

Transduced human PEP-1–catalase fusion protein attenuates ischemic neuronal damage

Antioxidant enzymes are considered to have beneficial effects against various diseases mediated by reactive oxygen species (ROS). Ischemia is characterized by both oxidative stress and changes in the antioxidant defense system. Catalase (CAT) and superoxide dismutase (SOD) are major antioxidant enzymes by which cells counteract the deleterious effects of ROS. To investigate the protective effects of CAT, we constructed PEP-1–CAT cell-permeative expression vectors. When PEP-1–CAT fusion proteins were added to the culture medium of neuronal cells, they rapidly entered the cells and protected them against oxidative stress-induced neuronal cell death. Immunohistochemical analysis revealed that PEP-1–CAT prevented neuronal cell death in the hippocampus induced by transient forebrain ischemia. Moreover, we showed that the protective effect of PEP-1–CAT was observed in neuronal cells treated with PEP-1–SOD. Therefore, we suggest that transduced PEP-1–CAT and PEP-1–SOD fusion proteins could be useful as therapeutic agents for various human diseases related to oxidative stress, including stroke.     

Countermeasures against space radiation induced oxidative stress in mice

Of particular concern for the health of astronauts during space travel is radiation from protons and high atomic number (Z), high energy particles (HZE particles). Space radiation is known to induce oxidative stress in astronauts after extended space flight. In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by proton and HZE particle radiation in the plasma of CBA mice and the protective effect of dietary supplement agents. The results indicate that exposure to proton and HZE particle radiation significantly decreased the plasma level of total antioxidants in the irradiated CBA mice. Dietary supplementation with l-selenomethionine (SeM) or a combination of selected antioxidant agents (which included SeM) could partially or completely prevent the decrease in the total antioxidant status in the plasma of animals exposed to proton or HZE particle radiation. These findings suggest that exposure to space radiation may compromise the capacity of the host antioxidant defense system; this adverse biological effect can be prevented at least partially by dietary supplementation with agents expected to have effects on antioxidant activities.     

Nutrition- and virus-induced stress represses the expression of manganese superoxide dismutase in vitro

The relationship between oxidative stress and neuronal cell death has been suggested for many years. To understand the influence of oxidative stress on neuronal cell death, we investigated the influence of oxidative stress on DEV cells, a human glial cell line. Using enterovirus infection and/or malnutrition to induce oxidative stress, our results demonstrate that those stressors severely influence the antioxidant defense system in DEV cells. Although the expression of mitochondrial manganese superoxide dismutase (MnSOD) in DEV cells was significantly increased in acute infection with viral and nutritional stress, in persistent infection and nutritional stress, the expression of the MnSOD was drastically downregulated. We believe that this downregulation of MnSOD expression in the chronic stress model is due to repression of antioxidant defense. The downregulation of the MnSOD expression may lead to an increase of free-radical production and thus explain why the cells in the chronic stress model were more vulnerable to other oxidative stress influences. The vulnerability of DEV cells to additional stress factors resulted in progressive cell death, which may be analogous to the cell death in neurodegenerative diseases.     

植物蛋白酶抑制素抗虫作用的研究进展

植物自身为抵抗昆虫等的为害,在长期进化过程中形成了复杂的化学防御体系,其中起主导作用的是一些植物化学物质。这些化合物能影响昆虫（或其它有机体）的生长、行为和群体生物学,因而又称为它感素（allelochemics）[1～3]。大多数它感素为植物的利己素,可以单一或协同对害虫起作用,构成植物的抗虫性。根据植物对昆虫取食的反应,可将植物的化学防御概括为两类：一类是组成型防御[4],即抗虫物质不依赖于昆虫的取食而存在于植物组织中;另一类是诱导型防御[5～9],即植物仅当昆虫取食时才大量合成抗虫物质。诱导型抗虫物质当然亦可以组…     

Analysis of cytotoxic effects of chlorhexidine gluconate as antiseptic agent on human blood lymphocytes

The aim of this study was to assess the cytotoxicity of chlorhexidine gluconate (CHG) on human blood lymphocytes as a useful ex vivo model for accelerated human toxicity studies. Using biochemical and flow cytometry assessments, we demonstrated that addition of CHG at 1 μM concentration to human blood lymphocytes induced cytotoxicity following 6 h. The CHG‐induced cytotoxicity on human blood lymphocytes was associated with intracellular reactive oxygen species generation, mitochondrial membrane potential collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione. According to our results, CHG triggers oxidative stress and organelles damages in lymphocytes which are important cells in defense against foreign agents. Finally our findings suggest that using of antioxidants and mitochondrial/lysosomal protective agents could be of benefit for the people in the exposure with CHG.     

Status of the antioxidant protective system of rat liver exposed to carbon tetrachloride]

The dynamics of enzyme activity of antioxidative protective system of the liver and the content of restored glutathione have been studied in rats poisoned by CCl4 injection. During the first hours followed the injection against the background of maximum accumulation of dienic conjugates and decrease of the restored glutathione level no significant changes in the enzyme activity of the antioxidative protective liver system were observed. At the same time 48 hours later the superoxide dismutase and catalase activity decreased by 38% and 36%, respectively, with relative stability of glutathione-dependent enzymes and a two-fold increase of the restored glutathione level. It is shown that a fall of activity of the cytoplasmic antioxidative liver enzymes is not a result of the immediate inactivating effect of free-radical reactions initiated by CCl4, but is, evidently, caused by the covalent binding of its radical metabolites with corresponding macromolecules.