Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study is to examine whether polysaccharide krestin, a protein-bound polysaccharide, can prevent the progression of atherosclerosis and lipoperoxidative injury caused by oxidatively modified low density lipoprotein (Ox-LDL) to macrophages. The alterations of GSHPx (glutathione peroxidase), SOD (superoxide dismutase) activity and NO (nitric oxide) release in PSK-treated mouse peritoneal macrophages, and the effect of LPS on them were investigated. With peritoneal injection of PSK, the following were observed in the mouse peritoneal macrophages: 1) an increase in SeGSHPx activity, 2) elevation in non-SeGSHPx and SOD activity; 3) the enzyme activities were further improved by addition of lipopolysaccharide (LPS); and 4) much NO was found to be released by PSK-treated mouse peritoneal macrophages stimulated by LPS.
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PMID:A protein-bound polysaccharide synergistic with lipopolysaccharide induces nitric oxide release and antioxidant enzyme activities in mouse peritoneal macrophages. 979 65

Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. In terms of its scavenging activity, melatonin has been shown to quench the hydroxyl radical, superoxide anion radical, singlet oxygen, peroxyl radical, and the peroxynitrite anion. Additionally, melatonin's antioxidant actions probably derive from its stimulatory effect on superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase and its inhibitory action on nitric oxide synthase. Finally, melatonin acts to stabilize cell membranes, thereby making them more resistant to oxidative attack. Melatonin is devoid of prooxidant actions. In models of oxidative stress, melatonin has been shown to resist lipid peroxidation induced by paraquat, lipopolysaccharide, ischemia-reperfusion, L-cysteine, potassium cyanide, cadmium chloride, glutathione depletion, alloxan, and alcohol ingestion. Likewise, free radical damage to DNA induced by ionizing radiation, the chemical carcinogen safrole, lipopolysaccharide, and kainic acid are inhibited by melatonin. These findings illustrate that melatonin, due to its high lipid solubility and modest aqueous solubility, is able to protect macromolecules in all parts of the cell from oxidative damage. Melatonin also prevents the inhibitory action of ruthenium red at the level of the mitochondria, thereby promoting ATP production. In humans, the total antioxidative capacity of serum is related to melatonin levels. Thus, the reduction in melatonin with age may be a factor in increased oxidative damage in the elderly.
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PMID:Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin. 992 48

Resveratrol (trans-3,4',5-trihydroxystibene) is a phytopolyphenol isolated from the seeds and skins of grapes. Recent studies indicate that resveratrol can block the process of multistep carcinogenesis, namely, tumor initiation, promotion and progression. Resveratrol can also reduce the risk of cardiovascular disease in man. The molecular mechanisms of resveratrol in chemoprevention of cancer and cardiovascular disease are interesting and under intensive investigation. Resveratrol was found to strongly inhibit nitric oxide (NO) generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic inducible nitric oxide synthase (iNOS) protein. The activation of nuclear factor kappa B (NF kappa B) induced by lipopolysaccharide (LPS) was inhibited by resveratrol. The phosphorylation and degradation of nuclear factor inhibitor kappa B alpha (I kappa B alpha) were inhibited by resveratrol simultaneously. Reactive oxygen species (ROS) are regarded as having carcinogenic potential and have been associated with tumor promotion. Resveratrol may act as a reactive oxygen species scavenger to suppress tumor development. In addition, resveratrol may block multistep carcinogenesis through mitotic signal transduction blockade. Reactive oxygen species are pivotal factors in the genesis of heart disease. Meanwhile, efficient endogenous antioxidants, including superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase, are present in tissues. A fine balance between reactive oxygen species and endogenous antioxidants is believed to exist. Any disturbance of this balance in favor of reactive oxygen species causes an increase in oxidative stress and initiates subcellular changes, leading to cardiomyopathy and heart failure. The experimental results indicate that exogenous antioxidant resveratrol is of value in chemopreventing the development of heart disease. It is urgent that more efforts be made to investigate newer therapies employing antioxidants for the chemoprevention of cardiovascular disease and cancer.
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PMID:Chemoprevention of cancer and cardiovascular disease by resveratrol. 1049 90

The objective of this study was to compare the prophylactic effects of the natural antioxidant from spinach (NAO) and apocynin, on the hepatic oxidative stress and liver damage induced by lipopolysaccharide (LPS). Male New Zealand rabbits were challenged with LPS with or without 8 days of antioxidant pretreatment. Pretreatment with NAO, but not apocynin, significantly (p < 0.05) decreased the levels of hydroperoxides and malondialdehyde (MDA) in the liver cytosolic fraction and the activity of NADPH oxidase-generated superoxide in the microsomal fraction, compared to LPS alone. The activity of glutathione peroxidase (G-POX) was significantly (p < 0.05) increased in the LPS-treated group, whereas treatment with NAO, but not apocynin, significantly (p < 0.05) decreased G-POX activity. Pretreatment with the same antioxidants had no significant effects on superoxide dismutase (SOD) activity, whereas an increased level of catalase (CAT) was obtained in all LPS-treated groups. TUNEL immunohistochemical staining in the LPS-treated animals indicated that there was no increase in apoptosis outside of necrotic foci. However, apoptotic hepatocytes were observed within areas of focal necrosis in animals exposed to LPS alone or LPS plus apocynin. Hepatocyte cell proliferation was tested by the proliferating-cell nuclear antigen (PCNA) tool, which indicated a proliferative effect in the LPS group, whereas the effect disappeared in the antioxidant-treated groups. The prophylactic effect of NAO on liver pathology and the significant decreases in lipid peroxidation products and NADPH oxidase activity suggest the use of NAO as an efficient strategy for treatment of endotoxemia.
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PMID:Effect of natural antioxidants and apocynin on LPS-induced endotoxemia in rabbit. 1121 Dec 38

Activation of polymorphonuclear cells (PMNs) leads to the formation of superoxide, which is in turn dismutated to H2O2 by superoxide dismutase (SOD) and is partly responsible for oxygen-dependent microbicidal activity. However, no comparative information is available on the effect of SOD inhibition before PMN activation to allow simulation of the SOD defects that are known to occur in some ruminants. This paper attempts to examine the degranulative and phagocytic responses in buffalo, cattle and goat PMNs exposed to diethyldithiocarbamate, a known SOD inhibitor. The activity of glutathione peroxidase and reductase was increased in the presence of SOD inhibitor. On activation, H2O2 production increased significantly (p < 0.01), while SOD inhibition before the activation of PMNs caused a significant decline in the production of H2O2 (p < 0.05) in all the species studied. There was a significant increase (p < 0.05) in the phagocytosis of Candida albicans spores by buffalo PMNs activated with opsonized zymosan. Activation of bovine PMNs after exposure to the SOD inhibitor resulted in a significant decline (p < 0.05) in phagocytic activity; in the other species, the two values only approached significance. Among the activators, opsonized zymosan caused a significant increase in phagocytic activity as compared to lipopolysaccharide, particularly in the PMNs of buffaloes (p < 0.05). Increased fungicidal activity (p < 0.05) occurred with opsonized zymosan-activated PMNs of all the species studied. The fungicidal activity was found to decline in PMNs exposed to SOD inhibitor before activation (p < 0.05). Interestingly, the phagocytic activity of caprine PMNs was found to be lower than that of PMNs from cattle (p < 0.05).
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PMID:Evaluation of oxygen-dependent immunodefences of the polymorphonuclear cells of some tropical ruminants. 1130 42

The present study was designed to evaluate the possible protective effect of quercetin, coenzyme Q10 (CoQ10), or L-canavanine treatments against endotoxin-induced shock in rat brain. Shock was induced by i.p. injection of 10 mg x kg(-1)of lipopolysaccharide (LPS) and was biochemically manifested 2 h after injection as an increase in brain malondialdehyde (MDA), total nitrite/nitrate (NO(x)), glutathione peroxidase (GSHPx), and blood lactate level/activity. On the other hand, endotoxemia resulted in reduced brain glutathione (GSH) and phospholipids' content as well as the serum sulfhydryl groups' (SH-group) value. Pretreatment with quercetin (200 mg x kg(-1)per os) 2 h before LPS injection diminished the shock-induced increases in brain MDA, and NO(x)levels while elevating the reduced brain phospholipids' and serum SH groups' content. CoQ10 administered at a dose of 200 mg x kg(-1)per os for 7 days prior to shock induction, reduced the elevated levels of brain MDA, NO(x), and GSHPx level/activity due to redundancy. The same treatment caused a 3-fold increase in the reduced brain GSH level and normalized the depressed phospholipids' content. Treatment of animals with L-canavanine (50 mg x kg(-1)i.p.) simultaneously with LPS injection, reduced the elevated level of blood lactate. Brain superoxide dismutase (SOD) level was neither affected by endotoxin nor by different treatments. In conclusion, this study indicates that SOD may not reflect the level of peroxidation and points to the value of quercetin, CoQ10, and L-canavanine in ameliorating the oxidative status of brain during the early phase of endotoxic shock.
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PMID:Quercetin, coenzyme Q10, and L-canavanine as protective agents against lipid peroxidation and nitric oxide generation in endotoxin-induced shock in rat brain. 1140 18

This study investigated the role of glutathione peroxidase-1 (GPX1) in protein oxidation in peritoneal macrophages. Macrophages isolated from both wild-type (WT) and GPX1 knockout (KO) mice were activated by lipopolysaccharide (LPS, 1 microg/ml) and interferon-gamma (IFN, 10 U/ml for 24 or 48 h in the presence or absence of 1 microM diquat (DQ), 250 microM aminoguanidine (AG, an inhibitor of inducible nitric oxide synthase), and (or) 100 microM diethyldithiocarbamate (DETC, an inhibitor of Cu,Zn-SOD). In the KO macrophages, there was no protein band detected by Western blot with anti-GPX1 antibody and 98% reduction in total GPX activity compared with WT cells. Nitric oxide (NO) synthesis was greatly enhanced after 24 h by GPX1 knockout and DQ, but inhibited by AG or DETC. Protein carbonyl formation in total cell extract was clearly associated with NO synthesis as higher levels of protein carbonyl were detected in activated KO than WT macrophages, and DQ enhanced slightly while AG or DETC virtually blocked its formation. A similarly marginal effect of GPX1 KO was observed on protein nitration. The LPS/IFN/DQ-induced DNA fragmentation was blocked by AG, but not by DETC. Cell viability at 48 h was decreased by the LPS/IFN activation and further reduced by the addition of DQ, but restored by AG. In conclusion, GPX1 affects the NO production in activated peritoneal macrophages and protects these cells against NO-associated protein oxidation.
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PMID:Lipopolysaccharide and interferon-gamma-induced nitric oxide production and protein oxidation in mouse peritoneal macrophages are affected by glutathione peroxidase-1 gene knockout. 1149 78

Oxidative damage plays a key role in septic shock induced by lipopolysaccharide (LPS) which is known to enhance the formation of reactive oxygen species (ROS). In this study, biochemical parameters indicative of oxidative stress were tested in the rat heart following LPS challenge, with and without pretreatment with the antioxidants NAO (natural antioxidant) and apocynin. NAO is a natural antioxidant isolated and purified from spinach and its main components are flavonoids and coumaric acid derivatives. Treatment with LPS alone significantly (P<0.05) increased the malondialdehyde (MDA) level in heart, both in cytosolic and mitochondrial fractions by 1.5- and 2.4-fold, respectively, and in plasma (2.66 fold). In the heart homogenate, the level of hydroperoxides also increased significantly (P<0.05). In addition, LPS treatment significantly (P<0.05) increased NADPH oxidase activity in the heart microsomal fraction by approximately 10-fold compared to control. Pretreatment for 7 days with either apocynin or NAO prior to the LPS challenge significantly (P<0.05) improved rat survival, decreased MDA levels in both fractions and decreased microsomal NADPH-oxidase activity, compared to LPS alone. Catalase (CAT) activity slightly increased at 24 h post-LPS injection in LPS group and returned to the control level in the apocynin treated group. No meaningful changes were indicated for glutathione peroxidase activity among all the treatment groups. The activities of cytosolic and mitochondrial superoxide dismutase (SOD) enzymes significantly (P<0.05) increased approximately 20% in the LPS-treated group, compared to control. Apocynin significantly (P<0.05) decreased SOD level in the mitochondrial fraction with no effect on the cytosolic fraction; whereas, NAO had no important effect on SOD level in both fractions. The beneficial pretreatment effects of the antioxidants against oxidative stress in the rat heart presented in this study may suggest a potential chemopreventive effect of this compound in sepsis prevention.
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PMID:The effect of natural antioxidants, NAO and apocynin, on oxidative stress in the rat heart following LPS challenge. 1151

To investigate the relevance of *NO and oxyradicals in the blood-brain barrier (BBB), differentiated and well-proliferating brain capillary endothelial cells (BCEC) are required. Therefore, rat BCEC (rBCEC) were transfected with immortalizing genes. The resulting lines exhibited endothelial characteristics (factor VIII, angiotensin-converting enzyme, high prostacyclin/thromboxane release rates) and BBB markers (gamma-glutamyl transpeptidase, alkaline phosphatase). The control line rBCEC2 (mock transfected) revealed fibroblastoid morphology, less factor VIII, reduced gamma-glutamyl transpeptidase, weak radical defence, low prostanoid metabolism, and limited proliferation. Lines transfected with immortalizing genes (especially rBCEC4, polyoma virus large T antigen) conserved primary properties: epitheloid morphology, subcultivation with high proliferation rate under pure culture conditions, and powerful defence against reactive oxygen species (Mn-, Cu/Zn-superoxide dismutase, catalase, glutathione peroxidase, glutathione) effectively controlling radical metabolism. Only 100 microM H2O2 overcame this defence and stimulated the formation of eicosanoids similarly as in primary cells. Some BBB markers were expressed to a lower degree; however, cocultivation with astrocytes intensified these markers (e.g., alkaline phosphatase) and paraendothelial tightness, indicating induction of BBB properties. Inducible NO synthase was induced by a cytokine plus lipopolysaccharide mixture in all lines and primary cells, resulting in *NO release. Comparing the cell lines obtained, rBCEC4 are stable immortalized and reveal the best conservation of properties from primary cells, including enzymes producing or decomposing reactive species. These cells can be subcultivated in large amounts and, hence, they are suitable to study the role of radical metabolism in the BBB and in the cerebral microvasculature.
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PMID:*NO and oxyradical metabolism in new cell lines of rat brain capillary endothelial cells forming the blood-brain barrier. 1151 40

Ebselen, a seleno-organic compound showing glutathione peroxidase-like activity, is one of the promising synthetic antioxidants. In the present study, we investigated the antioxidant activities of ebselen using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated mouse skin model. Double pretreatments of mouse skin with ebselen significantly inhibited TPA-induced formation of thiobarbituric acid-reacting substance, known as an overall oxidative damage biomarker, in mouse epidermis, suggesting that ebselen indeed acts as an antioxidant in mouse skin. The antioxidative effect of ebselen is attributed to its selective blockade of leukocyte infiltration and activation leading to attenuation of the H(2)O(2) level. In in vitro studies, ebselen inhibited TPA-induced superoxide generation in differentiated HL-60 cells and lipopolysaccharide-induced cyclooxygenase-2 protein expression in RAW 264.7 cells. In addition, we demonstrated for the first time that ebselen potentiated phase II enzyme activities, including NAD(P)H:(quinone-acceptor) oxidoreductase1 and glutathione S-transferase in cultured hepatocytes and in mouse skin. These results strongly suggest that ebselen, a multifunctional antioxidant, is a potential chemopreventive agent in inflammation-associated carcinogenesis.
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PMID:Ebselen, a glutathione peroxidase mimetic seleno-organic compound, as a multifunctional antioxidant. Implication for inflammation-associated carcinogenesis. 1171 17


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