Oxidative stress in malaria parasite-infected erythrocytes

Host-parasite interactions

Katja Becker, Leann Tilley, Jonathan L Vennerstrom, David Roberts, Stephen Rogerson, Hagai Ginsburg

Research output: Contribution to journalArticle

371 Citations (Scopus)

Abstract

Experimenta naturae, like the glucose-6-phosphate dehydrogenase deficiency, indicate that malaria parasites are highly susceptible to alterations in the redox equilibrium. This offers a great potential for the development of urgently required novel chemotherapeutic strategies. However, the relationship between the redox status of malarial parasites and that of their host is complex. In this review article we summarise the presently available knowledge on sources and detoxification pathways of reactive oxygen species in malaria parasite-infected red cells, on clinical aspects of redox metabolism and redox-related mechanisms of drug action as well as future prospects for drug development. As delineated below, alterations in redox status contribute to disease manifestation including sequestration, cerebral pathology, anaemia, respiratory distress, and placental malaria. Studying haemoglobinopathies, like thalassemias and sickle cell disease, and other red cell defects that provide protection against malaria allows insights into this fine balance of redox interactions. The host immune response to malaria involves phagocytosis as well as the production of nitric oxide and oxygen radicals that form part of the host defence system and also contribute to the pathology of the disease. Haemoglobin degradation by the malarial parasite produces the redox active by-products, free haem and H2O2, conferring oxidative insult on the host cell. However, the parasite also supplies antioxidant moieties to the host and possesses an efficient enzymatic antioxidant defence system including glutathione- and thioredoxin-dependent proteins. Mechanistic and structural work on these enzymes might provide a basis for targeting the parasite. Indeed, a number of currently used drugs, especially the endoperoxide antimalarials, appear to act by increasing oxidant stress, and novel drugs such as peroxidic compounds and anthroquinones are being developed.

Original languageEnglish (US)
Pages (from-to)163-189
Number of pages27
JournalInternational Journal for Parasitology
Volume34
Issue number2
DOIs
StatePublished - Jan 1 2004

Fingerprint

Host-Parasite Interactions
Malaria
Oxidation-Reduction
Parasites
Oxidative Stress
Erythrocytes
Pharmaceutical Preparations
Reactive Oxygen Species
Antioxidants
Pathology
Glucosephosphate Dehydrogenase Deficiency
Hemoglobinopathies
Thioredoxins
Thalassemia
Antimalarials
Sickle Cell Anemia
Heme
Phagocytosis
Oxidants
Glutathione

Keywords

  • Antimalarial drugs
  • Antioxidant enzymes
  • Glutathione
  • Oxidative stress
  • Plasmodium
  • Redox metabolism

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Oxidative stress in malaria parasite-infected erythrocytes : Host-parasite interactions. / Becker, Katja; Tilley, Leann; Vennerstrom, Jonathan L; Roberts, David; Rogerson, Stephen; Ginsburg, Hagai.

In: International Journal for Parasitology, Vol. 34, No. 2, 01.01.2004, p. 163-189.

Research output: Contribution to journalArticle

Becker, Katja ; Tilley, Leann ; Vennerstrom, Jonathan L ; Roberts, David ; Rogerson, Stephen ; Ginsburg, Hagai. / Oxidative stress in malaria parasite-infected erythrocytes : Host-parasite interactions. In: International Journal for Parasitology. 2004 ; Vol. 34, No. 2. pp. 163-189.
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