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

Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2.- into H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of CuZnSOD to determine whether overexpression of CuZnSOD affected the susceptibility of these mice to plasmodium infection. Acute malaria is associated with oxidative stress, mediated by redox-active iron released from the infected RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD mice were more vulnerable than control mice, the levels of parasitemia were comparable in both strains. Moreover, treatment of infected red blood cells (RBC) with oxidative stress inducers, such as ascorbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC. This further confirms that increased CuZnSOD does not support plasmodia development. The data are consistent with the possibility that the combination of increased redox-active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to an enhanced Fenton's reaction-mediated HO. production, and the resulting oxidative injury renders the transgenic mice more vulnerable to parasite infection.
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PMID:Transgenic mice with elevated level of CuZnSOD are highly susceptible to malaria infection. 964 Dec 69

Reactive oxygen species are important mediators of tissue injury during malaria infection. The status of hepatic oxidative stress and antioxidant defence indices were studied during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and chloroquine/ polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly ICLC) treatment of infected mice. P. y. nigeriensis infection resulted in a significant increase in oxidative stress indices viz., xanthine oxidase and rate of lipid peroxidation (LPO). This was accompanied by a highly significant increase in antioxidant defence indices viz., reduced glutathione (GSH) and glutathione reductase while superoxide dismutase (SOD) and catalase showed a highly significant decrease with respect to normal mice. Chloroquine treatment of infected mice caused a decrease in parasitaemia which was associated with restoration of indices altered during infection towards normalization. Poly ICLC treatment of infected mice caused no change in blood parasitaemia but resulted in a significant increase in GSH, glutathione reductase, SOD and catalase with respect to infected mice. Combination therapy of chloroquine and poly ICLC resulted in clearance of parasitaemia and restoration of all oxidative stress and antioxidant defence indices to normal levels.
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PMID:Studies on hepatic oxidative stress and antioxidant defence system during chloroquine/poly ICLC treatment of Plasmodium yoelii nigeriensis infected mice. 1039 Nov 38

Oxidant stress is associated with the generation of reactive oxygen species that are responsible for the damage of a variety of cellular components. The prevention of such biological damage can be achieved by dismutation of superoxide to H2O2 which in turn is removed by catalase and GSH peroxidase. However, redox-active iron released during the development of plasmodia in the erythrocyte can mediate the conversion of H2O2 to hydroxyl radical which is more reactive. The roles of SOD and the nitroxide SOD mimic 4-OH,2,2,6,6,tetramethyl piperidine-N-oxyl (Tempol) were examined in P. falciparum grown in vitro. Both compounds did not prevent the interference with growth inflicted by various inducers of oxidant stress. Moreover, Tempol inhibited parasite growth, in agreement with previous experiments depicting accelerated mortality in SOD overexpressing mouse model of malaria. Probably, effective defense against ROS requires balanced increments in antioxidant enzymes and is not necessarily improved by an increase in the activity of one enzyme.
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PMID:The role of superoxide dismutation in malaria parasites. 1044 98

Reactive Oxygen species play an important role in pathology during malaria infection. The status of hepatic oxidative stress and antioxidant defence indices was studied during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection in mice and arteether treatment of P. y. nigeriensis infected mice. P. y. nigeriensis infection caused a significant increase in hepatic xanthine oxidase, rate of lipid peroxidation, reduced glutathione (GSH) and glutathione reductase with progressive rise in parasitemia. This was accompanied by a significant decrease in hepatic superoxide dismutase (SOD) and catalase with increase in parasitemia. Arteether treatment (10 mg/kg body weight of mice) of infected mice from day 2 of post infection resulted in complete clearance of parasitemia on day 4 of post infection which was accompanied by restoration of all the oxidative stress and antioxidant defence indices to normal levels.
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PMID:Studies on hepatic oxidative stress and antioxidant defence systems during arteether treatment of Plasmodium yoelii nigeriensis infected mice. 1044 17

Desferal, N-acetyl penicillamine (metal chelators) and propylgallate, catechin, and reduced glutathione (antioxidants) suppressed the erythrocytic oxidative damage generated during Plasmodium berghei infection in Mastomys coucha. Superoxide anion and lipid peroxide levels were increased and on the contrary, superoxide dismutase activity was noticeably decreased in the infected erythrocytes. Metal chelators/antioxidant treatment to infected animals resulted in restoration of O(2)(-), LPO and SOD to near normal levels. Furthermore, treatment of the above mentioned agents displayed a controlled mortality/survival time and parasitaemia. In conclusion, metal chelators/antioxidants were found to be effective against oxidative stress injury and parasite growth resulting in prolonged survival time of the host during experimental malaria.
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PMID:Metal chelators/antioxidants: approaches to protect erythrocytic oxidative stress injury during Plasmodium berghei infection in Mastomys coucha. 1047 67

To assess the extent of oxidative stress in erythrocytes of patients with acute Plasmodium falciparum malaria, erythrocyte thiobarbituric acid-reactive substance (ETBAR), and intracellular, membrane and extracellular antioxidants were estimated in 102 cases of P. falciparum malaria and 50 control subjects. The mean concentration of ETBAR was significantly higher (P < 0.001) and many of the antioxidants were significantly lower in patients than controls. Among the erythrocyte antioxidants, catalase, reduced glutathione (GSH) and tocopherol were significantly lower in the patients (P < 0.05, 0.001, 0.001, respectively). Erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were not reduced to a statistically significant level. Similarly, the plasma antioxidants ascorbate and albumin were significantly lower (P < 0.001) but not urate. ETBAR correlated inversely with erythrocyte GSH and tocopherol (P < 0.001), and plasma ascorbate and albumin (P < 0.001) but not with the erythrocyte enzymic antioxidants. However, on multiple regression analysis only tocopherol correlated strongly with ETBAR, followed by GSH and plasma ascorbate. ETBAR also correlated well with haemolytic indices such as haemoglobin, plasma unconjugated bilirubin and haptoglobin concentrations (P < 0.001, for all). On follow-up after 2 weeks, ETBAR and different antioxidants reached near control levels. These observations indicate an enhanced oxidative stress on erythrocytes in acute falciparum malaria that may contribute substantially to haemolysis and anaemia.
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PMID:Evidence for erythrocyte lipid peroxidation in acute falciparum malaria. 1049 92

The iron-containing superoxide dismutase (FeSOD) gene from three human malaria species, namely Plasmodium ovale, P. malariae and P. vivax, was amplified by polymerase chain reaction, cloned and then sequenced. Comparisons of their deduced amino acid sequences with that of the FeSOD from P. falciparum revealed a very low polymorphism at the FeSOD locus in human malaria species. One P. ovale and the P. vivax FeSOD genes presented the same nucleotide sequence as that of the P. falciparum strain HB3 whereas the second P. ovale and the P. malariae genes exhibited two punctual mutations. These mutations did not affect the function and structure of the enzyme. The FeSOD polymorphism was so low that no phylogenetic relationship among human malaria species could be proposed, but this conservative structure strengthened the potentiality of this enzyme as a possible target for antimalarial drugs.
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PMID:Cloning and characterization of iron-containing superoxide dismutase from the human malaria species Plasmodium ovale, P. malariae and P. vivax. 1059 26

Oxidative stress and antioxidative capacity of platelets and the relationship with thrombocytopenia were determined in patients with vivax malaria and compared with those of healthy subjects. Whole blood thrombocyte count, platelet superoxide dismutase and glutathione peroxidase activities of patients with vivax malaria were lower and platelet lipid peroxidation levels were higher in patients than those of healthy subjects. There was an important negative correlation between whole blood thrombocyte count and platelet lipid peroxidation level. The antioxidative mechanisms of thrombocytes were insufficient in malaria patients and caused oxidative stress. The oxidative damage of thrombocytes might be important in the ethiopathogenesis of thrombocytopenia occurring in malaria.
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PMID:Oxidative stress of platelets and thrombocytopenia in patients with vivax malaria. 1144 Jul 37

Malaria parasite homogenate, the lipid extracts, and an unsaturated fatty acid, linoleic acid, which have been shown to promote beta-hematin formation in vitro, were used to investigate the mechanism of hemozoin biosynthesis, a distinct metabolic function of the malaria parasite. In vitro beta-hematin formation promoted by Plasmodium yoelii homogenate, the lipid extracts, and linoleic acid were blocked by ascorbic acid, reduced glutathione, sodium dithionite, beta-mercaptoethanol, dithiothreitol, and superoxide dismutase. Oxidized glutathione did not show any effect. Preoxidized preparations of the lipids extracts or the P. yoelii homogenate failed to catalyze beta-hematin formation. Depletion of oxygen in the reaction mixtures also inhibited the lipid-catalyzed beta-hematin formation. Under the reaction conditions similar to those used for the in vitro beta-hematin formation assay, the antioxidants and reducing agents mentioned above, except the DTT and beta-mercaptoethanol, did not cause degradation of heme. beta-Hematin formation was also inhibited by p-aminophenol, a free radical chain reaction breaker. Hemozoin biosynthesis within the digestive vacuoles of the malaria parasite may be a lipid-catalyzed physiochemical reaction. An oxidative mechanism may be proposed for lipid-mediated beta-hematin formation, which may be mediated by generation of some free radical intermediates of heme.
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PMID:A physiochemical mechanism of hemozoin (beta-hematin) synthesis by malaria parasite. 1177 14

Phylogenetic studies of the genus Plasmodium have been performed using sequences of the nuclear, mitochondrial and plastid genes. Here we have analyzed the adenylosuccinate lyase (ASL) gene, which encodes an enzyme involved in the salvage of host purines needed by malaria parasites for DNA synthesis. The ASL gene is present in several eukaryotic as well as prokaryotic organisms and does not have repeat regions, which facilitates the accuracy of the alignment. Furthermore, it has been shown that ASL is not subject to positive natural selection. We have sequenced the ASL gene of several different Plasmodium species infecting humans, rodents, monkeys and birds and used the obtained sequences along with the previously known P. falciparum ASL sequence, for structural and phylogenetic analysis of the genus Plasmodium. The genetic divergence of ASL is comparable with that observed in other nuclear genes such as cysteine proteinase, although ASL cannot be considered conserved when compared to aldolase or superoxide dismutase, which exhibit a slower rate of evolution. Nevertheless, a protein like ASL has a rate of evolution that provides enough information for elucidating evolutionary relationships. We modeled 3D structures of the ASL protein based on sequences used in the phylogenetic analysis and obtained a consistent structure for four different species despite the divergence observed. Such models would facilitate alignment in further studies with a greater number of plasmodial species or other Apicomplexa.
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PMID:Phylogenetic analysis of the genus Plasmodium based on the gene encoding adenylosuccinate lyase. 1279 8


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