Oxidative stress of platelets and thrombocytopenia in patients with vivax malaria

Erel, Özcan; Vural, Hüseyín; Aksoy, Nurten; Aslan, Gönül; Ulukanlıgil, Mustafa

doi:10.1016/s0009-9120(01)00221-1

Cited by 75 publications

(44 citation statements)

References 10 publications

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“…Because (i) macrophages during malaria produce high levels of NO and superoxide (11,18,19,26,28), which react to form peroxynitrite (4), and (ii) superoxide and peroxynitrite reportedly kill the P. falciparum parasite in vitro (16), SIN-1 treatment was used to determine whether superoxide, nitric oxide, and peroxynitrite collectively have an effect on parasite viability. Parasitized RBCs were treated with 1 mM SIN-1 for 1 h in room air and at room temperature and then injected into mice.…”

Section: Resultsmentioning

confidence: 99%

Plasmodium bergheiResists Killing by Reactive Oxygen Species

et al. 2005

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Reactive oxygen species (ROS) are widely believed to kill malarial parasites. C57BL/6 mice injected with P. berghei inocula incubated with supraphysiological doses of NO (<150 M) or with peroxynitrite (220 M), however, exhibited parasitemia similar to that seen with those given control inocula, and there was no difference in disease development. Only treatment of inocula with NO doses nearing saturation (>1.2 mM) resulted in no detectable parasitemia in the recipients; flow cytometric analysis with a vital dye (hydroethidine) indicated that 1.5 mM NO lysed the erythrocytes rather than killing the parasites. The hemoglobin level in the inocula was about 8 M; the hemoglobin was mainly oxyhemoglobin (oxyHb) (96%), which was converted to methemoglobin (>95%) after treatment with 150 M NO. The concentrations of 150 M of NO and 220 M of peroxynitrite were far in excess of the hemoglobin concentration (ϳ8 M), and yet no parasite killing was detected. We therefore conclude that hemoglobin protects Plasmodium parasites from ROS, but the parasite likely possesses intrinsic defense mechanisms against ROS.Malaria, a reemerging disease (20) caused by the parasite of the genus Plasmodium, remains refractory to the development of a vaccine in part due to incomplete understanding of the mechanism(s) underlying parasite killing by the immune system. It is generally accepted that reactive oxygen species (ROS), including nitric oxide (NO), superoxide, and peroxynitrite, kill intraerythrocytic malarial parasites (5,8,29). The most cited mechanism for parasite killing is that acute Plasmodium infection induces gamma interferon-producing Th1 cells, which in turn activate macrophages to secrete parasiticidal NO and ROS (29,30).We propose, however, that the blood stage Plasmodium parasite is virtually immune to the cytotoxic effects of NO and ROS as a consequence of hemoglobin (Hb) NO scavenging and ROS suppression within red blood cells (RBCs). The Plasmodium parasite is surrounded by hemoglobin through most of its asexual blood cycle, because it resides within a parasitophorous vacuole inside erythrocytes. Plasmodium falciparum parasites rupture erythrocytes, releasing progeny merozoites, which invade new RBCs after completing their 48-hour blood stage cycle. This extracellular excursion constitutes a brief period in which the parasite is in principle vulnerable to higher ROS concentrations induced by the infection. However, the disruption of the RBC membrane inevitably releases molecular hemoglobin into the circulation, enhancing ROS scavenging; thus, both inside and outside the red cells the parasite is protected from ROS because ROS are scavenged by hemoglobin.Malaria, therefore, is fundamentally different from most infections, because the parasite is surrounded by hemoglobin and can evade the ROS-based protective mechanism as a consequence of ROS quenching by Hb (2), an antioxidant mechanism that has been overlooked. Although Hb's heme group can undergo redox transitions to higher oxidation states and it can auto-oxidize natural...

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Section: Resultsmentioning

confidence: 99%

Plasmodium bergheiResists Killing by Reactive Oxygen Species

et al. 2005

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“…Elevated M-CSF levels in malaria, by increasing macrophage activity may mediate platelet destruction in such cases [9]. Oxidative stress damage of thrombocytes has also been implicated in the etiopathogenesis based on the finding of low levels of platelet superoxide-dismutase and glutathioneperoxidase activity and high platelet lipid peroxidation levels in malaria patients, when compared to those of healthy subjects [10].…”

Section: Discussionmentioning

confidence: 99%

Plasmodium vivax malaria presenting with severe thrombocytopenia

et al. 2002

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Plasmodium falciparum and Plasmodium vivax malaria are endemic infections in India and are commonly associated with mild hematological abnormalities. Severe thrombocytopenia is common in isolated falciparum and mixed falciparum/vivax malaria, but is very rare in isolated P.vivax infection. We hereby report a case of severe thrombocytopenia (platelet count of 8x10 9 /L) in a case of vivax malaria. This is only the second case ever reported in the literature of such profound thrombocytopenia in a case of isolated P.vivax malaria. Key Words: Plasmodium vivax, malaria, severe thrombocytopenia. Malaria is common in most parts of India and is usually caused by P. falciparum and P. vivax. Though mild thrombocytopenia is common in both falciparum and vivax malaria, severe thrombocytopenia is reported especially in P. falciparum malaria and is very rare in isolated P. vivax infection. Both non-immunological as well as immunological destruction of platelets have been implicated in causing thrombocytopenia in such cases but the mechanisms involved are still not completely clear. Case ReportA 43-year-old male, resident of eastern India, arrived at the hospital emergency room with complaints of high grade, intermittent fever associated with chills and rigors during seven days. He also had a two-day history of mild spontaneous bleeding from the gums. There was no history of bleeding from any other site and no past or family history suggestive of bleeding diathesis. There was no history of any drug ingestion. On examination, the patient was febrile with a temperature of 40 o C. He had slight pallor and the liver and spleen were palpable 2 cm and 3 cm below the costal margin, respectively. There were no purpuric spots and the tourniquet test was negative.Routine blood investigations revealed 7.5 g/dL hemoglobin and a WBC count of 6.3x10 9 /L, with 54% neutrophils, 39% lymphocytes, 4% eosinophils and 3% monocytes. The platelet count was 8x10 9 /L. The peripheral blood smear showed numerous gametocytes of P. vivax in a background of marked thrombocytopenia. The 'OptiMAL® Rapid Malaria Dipstick Test' (DiaMed AG,Switzerland) for P. falciparum was negative but was positive for P. vivax. The bleeding time was prolonged to 9 minutes while the clotting time was 3 minutes, with a prothrombin time of 14 seconds (control 13 seconds) and activated partial thromboplastin time of 40 seconds (control 36 seconds). Glucose-6-phosphate dehydrogenase levels were normal and disseminated intravascular coagulation (DIC) was ruled out by normal levels of fibrinogen degradation products (FDP). Total serum bilirubin was 1.4 mg/dL with normal serum transaminase levels. Dengue serology (IgG and IgM) and Elisa for HIV were nonreactive. The patient was treated with antimalarials (quinine sulphate 10 mg/kg thrice daily) for 7 days and was given 6 units of platelet transfusions

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“…ROS species may have important functions in the structural and functional alterations of platelets and in the mechanism of trombocytopenia in malaria (Erel et al 2001). To characterize the role of OS in thrombocytopenia mediated by P. vivax infection, markers of OS and antioxidant status were analyzed in blood plasma and platelets of patients with vivax malaria.…”

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confidence: 99%