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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study has been made of counteracting the stress organ injury in Plasmodium infection by means of antioxidants on the premise that free radicals are responsible for causing the injury to stress organs. This was evidenced by drastically altered biochemical parameters in liver and spleen of the host in terms of elevated levels of lipid peroxides and xanthine oxidase (XO) activity, and a fall in superoxide dismutase activity coupled with other drastic biochemical changes. The cardinal factor responsible for the above was considered to be XO which engenders free radicals purportedly responsible for the stress organ (biochemical) injury. Results demonstrate a lowering of lipid peroxide levels, xanthine oxidase activity, liver weight and modulation of protein level in liver of the host (mouse) in Plasmodium infection when treated with catechin, glutathione and propylgallate.
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PMID:The antioxidants as protectors of host stress organ injury in mice infected with Plasmodium berghei. 269 64

To test the hypothesis that the resistance of sickle trait (AS Hgb) erythrocytes (rbcs) to malaria may be mediated by increased production of activated oxygen species, the production of superoxide anion (O2-) and hydrogen peroxide (H2O2) by AS rbcs and normal (AA Hgb) rbcs was measured under defined conditions. Formation of O2- and H2O2 was time, temperature and oxygen saturation dependent. Reproducible measurement of O2- formation required the presence of 0.2 mmol l-1 KCN to inhibit a cytochrome oxidase activity found in the cytochrome C preparation used. There was an inverse relationship between cell concentration and O2- and H2O2 formation. Use of the inhibitor of superoxide dismutase (SOD), diethyldithiocarbamic acid, increased the amount of O2- measured. When rbcs from blacks with AS Hgb and with AA Hgb were incubated under standardized conditions, significantly (P less than 0.05) more O2- was formed by AS than AA cells (24.3 v. 14.5 mmol per mol Hgb). These findings show that AS rbcs can generate more O2- than AA rbcs. The increased formation of O2- by rbcs containing AS Hgb may contribute to the resistance of AS rbcs to malarial parasitism.
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PMID:Generation of superoxide anion and hydrogen peroxide by erythrocytes from individuals with sickle trait or normal haemoglobin. 301 34

Cultured Plasmodium falciparum was retarded in intraerythrocytic development by serum from malaria-immune adults, by human TB serum, and by rabbit tumor necrosis serum. Neither the potency nor efficacy of any of these sera was altered by a variety of antioxidants or oxygen-free radial scavengers, including ascorbate, alpha-tocopherol, BHT, cystine or cysteine, glutathione, histidine, phenylalanine, tryptophan, tyrosine, superoxide dismutase, catalase (or combination of the two enzymes), or by reducing the ambient O2 tension to 1%. It is thus unlikely that the antiparasitic activity of these inhibitory sera can be attributed to oxidative mechanisms.
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PMID:Antioxidants do not prevent the in vitro induction of Plasmodium falciparum crisis forms by human malaria-immune, TB or rabbit TNF serum. 352 84

Plasmodium berghei, a murine malaria, lacks endogenous superoxide dismutase (SOD). Instead it appears to take up and concentrate SOD from its host cell, the erythrocyte. We now demonstrate that the adopted host enzyme is localized in granules which are probably lysosomes. In addition, isolated P. berghei parasites contain only low levels of catalase, probably as a result of contamination of the preparation with host cell material. Thus, the cytosol of this organism appears to be deficient in enzymes which protect against damage by activated oxygen.
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PMID:Superoxide dismutase and catalase in the murine malaria, Plasmodium berghei: content and subcellular distribution. 353 81

Aerobic organisms depend on superoxide dismutase to suppress the formation of dangerous species of activated oxygen. Intraerythrocytic stages of the malaria parasite exist within a highly aerobic environment and cause the generation of increased amounts of activated oxygen. Plasmodium berghei in mice was found to derive a substantial amount of superoxide dismutase activity from the host cell cytoplasm. Plasmodia isolated from mouse red cells contained mouse superoxide dismutase, whereas rat-derived parasites contained the rat enzyme. This is believed to be the first example of the acquisition of a host cell enzyme by an intracellular parasite.
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PMID:Malaria parasites adopt host cell superoxide dismutase. 634 44

The murine malaria parasite Plasmodium yoelii was killed in vitro when incubated with glucose and glucose oxidase, a system generating hydrogen peroxide, or with xanthine and xanthine oxidase, a system which produces the superoxide anion and subsequently other products of the oxidative burst. Catalase blocked the killing in both cases; superoxide dismutase and scavengers of hydroxyl radicals or singlet oxygen were ineffective in the xanthine oxidase system. Thus, hydrogen peroxide appears to be the main reactive oxygen species killing P. yoelii.
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PMID:Killing of Plasmodium yoelii by enzyme-induced products of the oxidative burst. 654 75

The capacity of macrophages activated in vivo and in vitro to kill Plasmodium yoelii was investigated. Macrophages activated by BCG-, Con A-, or malaria-induced lymphokines (LK) were cultured with P. yoelii-parasitized erythrocytes (PE). In some experiments, effector and target cells were separated by a 0.45-micron filter. Parasite viability was assessed a) in vivo by injection of mice and quantitative detection of parasites by RIA or b) in vitro by the incorporation of 3H amino acids into parasite proteins. Activated macrophages killed target PE in a dose-dependent manner by elaborating a membrane-permeable soluble factor(s). The addition of small amounts of immune serum augmented the killing of the parasites. LK-activated macrophages underwent an oxidative burst upon the phagocytosis of PE as evidenced by the accumulation of reduced formazan in the NBT assay. The magnitude of the oxidative response corresponded to the number of parasites that were ingested. The phagocytosis-induced oxidative burst was necessary for subsequent killing of Plasmodium. Parasites incubated in microchambers separated from macrophages by a 0.45-micron filter were susceptible to H2O2 released by LK-activated macrophages incubated with PMA, opsonized zymosan, or P. yoelii antigen. Inhibition of protein synthesis by parasites exposed to products of activated macrophages was abrogated by preincubating macrophages with catalase but not with SOD, mannitol, or histidine. These results suggest that phagocytosis-associated oxidative mechanisms mediate the destruction of the malaria parasite. Hence, cell-mediated as well as antibody-dependent mechanisms cooperate in the immune response against malaria.
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PMID:Oxidative killing of the intraerythrocytic malaria parasite Plasmodium yoelii by activated macrophages. 669 Jun 6

Cell-cell interactions are important in intravascular inflammation. Neutrophils and monocytes adhere to the vascular endothelium and release mediators, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and reactive oxygen species. Red blood cells (RBC) from patients with malaria, sickle cell anemia, and diabetes also adhere to endothelial cells. The objectives of this investigation were to develop a bovine system of RBC adhesion to endothelial cells and to begin to investigate the mechanisms involved in the RBC adhesion. We show that 51Cr-RBC adhere to bovine pulmonary artery endothelial cells (BPAEC) after stimulation of both cell types with endotoxin (ETX; 50 micrograms/ml). RBC adhesion to BPAEC depended on the ETX concentration and the presence of divalent cations. TNF-alpha, IL-1 beta, and antioxidants (superoxide dismutase; catalase; and dimethyl sulfoxide) all induced RBC adhesion to BPAEC. Phosphatidylserine, which has been implicated in adhesion of sickle cells and aged RBC to endothelium, reduced RBC adhesion to BPAEC, whether ETX-treated or not. In conclusion, ETX, proinflammatory cytokines and, surprisingly, antioxidants increase RBC adherence to BPAEC monolayers. RBC adhesion to endothelium is decreased by phosphatidylserine.
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PMID:Endotoxin-induced adhesion of red blood cells to pulmonary artery endothelial cells. 877 24

The various mechanisms involved in the redox defence of normal erythrocytes are adequately known. They are herein briefly reviewed, outlining the principal enzymes and metabolic pathways, such as superoxide dismutase, catalase, glutathione peroxidase and reductase, the hexose monophosphate shunt (HMS) and glutathione synthesis and turnover. The intraerythrocytic malaria parasite is imposing an oxidative stress on its host cell. Malaria infected cells produce O2-, H2O2, enhance lipide peroxidation and activate host cell HMS. This stress is produced during the digestion of host cell hemoglobin by the parasite. Hence, both parasite and host cell must be able to confront this stress. The antioxidant defence systems of the parasite and the response of those systems in the infected host cell are reviewed, underscoring unresolved problems. Nothing is virtually known on the parasite's glutathione metabolism, and on possible interactions between host cell and parasite antioxidant defence systems. The postulate that 1. host cell activated HMS in conjunction with purine salvage can provide purine nucleotides to the parasite, and 2. that glutathione transferase can participate in parasite resistance to antimalarial drugs, are also discussed.
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PMID:The redox status of malaria-infected erythrocytes: an overview with an emphasis on unresolved problems. 914 Apr 69

Riboflavin deficiency interferes with the growth and multiplication of malaria parasites as well as the host response to malaria. The objective of the present work was to determine the effects of riboflavin deficiency on erythrocyte glutathione peroxidase (EC 1.11.1.9; GPx) and superoxide dismutase (EC 1.15.1.1; SOD) in rats infected with Plasmodium berghei malaria. Riboflavin in its co-enzyme form, FAD, is required by glutathione reductase (EC 1.6.4.1) to regenerate GSH and GSH is an important cellular antioxidant both in its own right and also as a substrate for the enzyme GPx. Weanling rats were deprived of riboflavin for 8 weeks before intraperitoneal injection of 1 x 10(6) P. berghei parasites. Control animals were weight-matched to the respective riboflavin-deficient group. At 10 d post-infection, parasite counts were higher in the weight-matched control group than the riboflavin-deficient group (P = 0.004). GPx activity was higher in erythrocytes of rats parasitized with P. berghei than comparable non-infected rats regardless of riboflavin status (P < 0.05). As mature erythrocytes do not synthesize new protein, the higher GPx activities were probably due to the presence of the parasite protein. In erythrocytes from riboflavin-deficient rats, GPx activity tended to be lower than in those rats fed on diets adequate in riboflavin (weight-matched controls) whether parasitized or not, but the difference was not significant. Neither riboflavin deficiency nor malaria had any effect on erythrocyte SOD activity. It was concluded that riboflavin deficiency has no marked effect on erythrocyte GPx or SOD activity in the rat.
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PMID:Glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities in riboflavin-deficient rats infected with Plasmodium berghei malaria. 957 9


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