ArticlePloS one2015
Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Host Reticulocyte Redox Attenuation Creates a Protective Niche for Artemisinin Tolerance in Plasmodium falciparum.The Journal of infectious diseases · 2026Article
- Oral nanoliposomes functionalized with cRGD and polydopamine for enhanced antimalarial efficacy of disulfide bond-modified dihydroartemisinin prodrug.Drug delivery · 2025Article
- Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy.International journal of pharmaceutics: X · 2025Article
- Effect of walnut leaves on oxidative stress caused by murine cerebral malaria.Frontiers in cellular and infection microbiology · 2025Article
- Oxidative stress in malaria and typhoid fever: A scoping review of the pathogenic mechanisms and therapeutic implications.PLOS global public health · 2025Article
- Article
- Marine-DerivedMicroorganisms · 2023Article
- Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy.International journal of molecular sciences · 2022Review
- Differential Effect of Antioxidants Glutathione and Vitamin C on the Hepatic Injuries Induced byBioMed research international · 2021Article
- Plasmodium berghei K13 Mutations MediatemBio · 2020Article
- Experimentally Engineered Mutations in a Ubiquitin Hydrolase, UBP-1, ModulateAntimicrobial agents and chemotherapy · 2020Article
- Artemisinin-Based Antimalarial Drug Therapy: Molecular Pharmacology and Evolving Resistance.Tropical medicine and infectious disease · 2019Review
- A cryptic cycle in haematopoietic niches promotes initiation of malaria transmission and evasion of chemotherapy.Nature communications · 2018Article
- Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.BMC genomics · 2017Article
- Quantitative characterization of hemozoin in Plasmodium berghei and vivax.International journal for parasitology. Drugs and drug resistance · 2017Article
- ThePeerJ · 2017Article
- Article
- Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage.Free radical biology & medicine · 2016Article
- Superparamagnetic Properties of Hemozoin.Scientific reports · 2016Article
- Inhibition of Glutathione Biosynthesis Sensitizes Plasmodium berghei to Antifolates.Antimicrobial agents and chemotherapy · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Malaria is one of the most devastating parasitic diseases worldwide. Plasmodium drug resistance remains a major challenge to malaria control and has led to the re-emergence of the disease. Chloroquine (CQ) and artemisinin (ART) are thought to exert their anti-malarial activity inducing cytotoxicity in the parasite by blocking heme degradation (for CQ) and increasing oxidative stress. Besides the contribution of the CQ resistance transporter (PfCRT) and the multidrug resistant gene (pfmdr), CQ resistance has also been associated with increased parasite glutathione (GSH) levels. ART resistance was recently shown to be associated with mutations in the K13-propeller protein. To analyze the role of GSH levels in CQ and ART resistance, we generated transgenic Plasmodium berghei parasites either deficient in or overexpressing the gamma-glutamylcysteine synthetase gene (pbggcs) encoding the rate-limiting enzyme in GSH biosynthesis. These lines produce either lower (pbggcs-ko) or higher (pbggcs-oe) levels of GSH than wild type parasites. In addition, GSH levels were determined in P. berghei parasites resistant to CQ and mefloquine (MQ). Increased GSH levels were detected in both, CQ and MQ resistant parasites, when compared to the parental sensitive clone. Sensitivity to CQ and ART remained unaltered in both pgggcs-ko and pbggcs-oe parasites when tested in a 4 days drug suppressive assay. However, recrudescence assays after the parasites have been exposed to a sub-lethal dose of ART showed that parasites with low levels of GSH are more sensitive to ART treatment. These results suggest that GSH levels influence Plasmodium berghei response to ART treatment.
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