scholarly journals Peroxide Antimalarial Drugs Target Redox Homeostasis in Plasmodium falciparum Infected Red Blood Cells

2022 ◽  
Author(s):  
Ghizal Siddiqui ◽  
Carlo Giannangelo ◽  
Amanda De Paoli ◽  
Anna Katharina Schuh ◽  
Kim C. Heimsch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Redox Homeostasis ◽  
Antimalarial Drugs

scholarly journals In Vitro Assessment of Antiplasmodial Activity and Cytotoxicity of Polyalthia longifolia Leaf Extracts on Plasmodium falciparum Strain NF54

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Bethel Kwansa-Bentum ◽  
Kojo Agyeman ◽  
Jeffrey Larbi-Akor ◽  
Claudia Anyigba ◽  
Regina Appiah-Opong
Keyword(s):  
Plasmodium Falciparum ◽  
Ethyl Acetate ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Radical Scavenging ◽  
Antimalarial Drugs ◽  
Antiplasmodial Activity ◽  
Leaf Extracts ◽  
Polyalthia Longifolia

Background. Malaria is one of the most important life-threatening infectious diseases in the tropics. In spite of the effectiveness of artemisinin-based combination therapy, reports on reduced sensitivity of the parasite to artemisinin in Cambodia and Thailand warrants screening for new potential antimalarial drugs for future use. Ghanaian herbalists claim that Polyalthia longifolia has antimalarial activity. Therefore, antiplasmodial activity, cytotoxic effects, and antioxidant and phytochemical properties of P. longifolia leaf extract were investigated in this study. Methodology/Principal Findings. Aqueous, 70% hydroethanolic and ethyl acetate leaf extracts were prepared using standard procedures. Antiplasmodial activity was assessed in vitro by using chloroquine-sensitive malaria parasite strain NF54. The SYBR® Green and tetrazolium-based calorimetric assays were used to measure parasite growth inhibition and cytotoxicity, respectively, after extract treatment. Total antioxidant activity was evaluated using a free radical scavenging assay. Results obtained showed that extracts protected red blood cells against Plasmodium falciparum mediated damage. Fifty percent inhibitory concentration (IC50) values were 24.0±1.08 μg/ml, 22.5±0.12 μg/ml, and 9.5±0.69 μg/ml for aqueous, hydroethanolic, and ethyl acetate extracts, respectively. Flavonoids, tannins, and saponins were present in the hydroethanolic extract, whereas only the latter was observed in the aqueous extract. Aqueous and hydroethanolic extracts showed stronger antioxidant activities compared to the ethyl acetate extract. Conclusions/Significance. The extracts of P. longifolia have antiplasmodial properties and low toxicities to human red blood cells. The extracts could be developed as useful alternatives to antimalarial drugs. These results support claims of the herbalists that decoctions of P. longifolia are useful antimalarial agents.

scholarly journals Mode of action of quinoline antimalarial drugs in red blood cells infected by Plasmodium falciparum revealed in vivo

2019 ◽  
Vol 116 (46) ◽  
pp. 22946-22952 ◽  
Author(s):  
Sergey Kapishnikov ◽  
Trine Staalsø ◽  
Yang Yang ◽  
Jiwoong Lee ◽  
Ana J. Pérez-Berná ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Mode Of Action ◽  
Culture Medium ◽  
Crystal Surface ◽  
Membrane Surface ◽  
Antimalarial Drugs ◽  
Digestive Vacuole

The most widely used antimalarial drugs belong to the quinoline family. Their mode of action has not been characterized at the molecular level in vivo. We report the in vivo mode of action of a bromo analog of the drug chloroquine in rapidly frozen Plasmodium falciparum-infected red blood cells. The Plasmodium parasite digests hemoglobin, liberating the heme as a byproduct, toxic to the parasite. It is detoxified by crystallization into inert hemozoin within the parasitic digestive vacuole. By mapping such infected red blood cells with nondestructive X-ray microscopy, we observe that bromoquine caps hemozoin crystals. The measured crystal surface coverage is sufficient to inhibit further hemozoin crystal growth, thereby sabotaging heme detoxification. Moreover, we find that bromoquine accumulates in the digestive vacuole, reaching submillimolar concentration, 1,000-fold more than that of the drug in the culture medium. Such a dramatic increase in bromoquine concentration enhances the drug’s efficiency in depriving heme from docking onto the hemozoin crystal surface. Based on direct observation of bromoquine distribution in the digestive vacuole and at its membrane surface, we deduce that the excess bromoquine forms a complex with the remaining heme deprived from crystallization. This complex is driven toward the digestive vacuole membrane, increasing the chances of membrane puncture and spillage of heme into the interior of the parasite.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

Endothelin-1 production by a microvascular endothelial cell line treated with Plasmodium falciparum parasitized red blood cells

2002 ◽  
Vol 103 (s2002) ◽  
pp. 464S-466S ◽  
Author(s):  
Nicoletta BASILICO ◽  
Livianna SPECIALE ◽  
Silvia PARAPINI ◽  
Pasquale FERRANTE ◽  
Donatella TARAMELLI
Keyword(s):  
Plasmodium Falciparum ◽  
Endothelial Cell ◽  
Red Blood Cells ◽  
Cell Line ◽  
Blood Cells ◽  
Microvascular Endothelial Cell ◽  
Microvascular Endothelium ◽  
Endothelial Cell Line ◽  
Endothelin 1 ◽  
Microvascular Endothelial

In this study, we investigated the production of endothelin 1 (ET-1) by a human microvascular endothelial cell line, HMEC-1, co-cultured with Plasmodium falciparum-parasitized red blood cells (pRBCs). The results indicate that hypoxia increased the basal level of ET-1 production by HMEC-1 cells after 24 or 48h of treatment. However, the co-incubation of HMEC-1 cells with pRBCs, but not with uninfected RBCs, induced a dose-dependent decrease of both constitutive and hypoxia-induced ET-1 production. The inhibition was not due to a decrease in cell viability, as lactate dehydrogenase release remained constant. These results indicate that pRBCs are able to interfere with both the constitutive and stimulated ET-1 release from the microvascular endothelium, thus inducing local modifications of the vascular tone and of the inflammatory response. This could be of relevance in the pathogenesis of the most severe forms of P. falciparum infections, such as cerebral malaria or malaria during pregnancy.

scholarly journals Dielectric characterization of Plasmodium falciparum -infected red blood cells using microfluidic impedance cytometry

2018 ◽  
Vol 15 (147) ◽  
pp. 20180416 ◽  
Author(s):  
C. Honrado ◽  
L. Ciuffreda ◽  
D. Spencer ◽  
L. Ranford-Cartwright ◽  
H. Morgan
Keyword(s):  
Plasmodium Falciparum ◽  
Dielectric Properties ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Time Course ◽  
Fluorescent Protein ◽  
Clear Understanding ◽  
Infection Cycle ◽  
Dielectric Characterization ◽  
Impedance Cytometry

Although malaria is the world's most life-threatening parasitic disease, there is no clear understanding of how certain biophysical properties of infected cells change during the malaria infection cycle. In this article, we use microfluidic impedance cytometry to measure the dielectric properties of Plasmodium falciparum -infected red blood cells ( i- RBCs) at specific time points during the infection cycle. Individual parasites were identified within i- RBCs using green fluorescent protein (GFP) emission. The dielectric properties of cell sub-populations were determined using the multi-shell model. Analysis showed that the membrane capacitance and cytoplasmic conductivity of i- RBCs increased along the infection time course, due to membrane alterations caused by parasite infection. The volume ratio occupied by the parasite was estimated to vary from less than 10% at earlier stages, to approximately 90% at later stages. This knowledge could be used to develop new label-free cell sorting techniques for sample pre-enrichment, improving diagnosis.

scholarly journals Red blood cells release microparticles containing human argonaute 2 and miRNAs to target genes of Plasmodium falciparum

2017 ◽  
Vol 6 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Zhensheng Wang ◽  
Juemin Xi ◽  
Xiao Hao ◽  
Weiwei Deng ◽  
Juan Liu ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Target Genes ◽  
Argonaute 2

scholarly journals Comparative assessment of Chemosuppressive activity of three Chinese teas on Plasmodium berghei infected mice

2018 ◽  
Vol 7 (4) ◽  
pp. 376-383
Author(s):  
Bankole Olukayode Olusola ◽  
◽  
Oderinde Abdulganiyu Olumuyiwa ◽  
Keyword(s):  
Body Weight ◽  
Red Blood Cells ◽  
Plasmodium Berghei ◽  
Blood Cells ◽  
Haemoglobin Concentration ◽  
Treated Group ◽  
Antimalarial Drugs ◽  
Comparative Assessment ◽  
Haematological Parameters ◽  
Weight Changes

Malaria, a hazardous infirmity caused by a parasitic malady of the red blood cells, is without question harming to the wellbeing. In the present investigation, the chemosuppresive and haematopoietic activities of 200 mg/kg and 400 mg/kg body weight of unrefined ethanolic concentrates of three Chinese green teas (BIA 849, TD 570 and GB/T19598) were assessed using the 4-day suppressive anti-plasmodial assay in mice Plasmodium berghei (NK65 strain) pre-infected mice. The effect of the extracts on weight of the animals was evaluated. It was observed that 200 mg/kg bw (body weight) of BIA 849 and GB/T19598 were as potent as 5 mg/kg bw of chloroquine, with percentage suppressions of 58.97 ± 5.04, 57.63 ± 5.62 and 57.50 ± 4.5, respectively. TD570 at 200 mg/kg bw was more effective in suppressing plasmodium. 400 mg/kg body weight of TD570 and GB/T19598 extracts were more potent than 5 mg/kg bw of chloroquine having 100 % chemosuppression. The chemosuppression of BIA 849 did not change altogether at 400 mg/kg bw. The haematological parameters, WBC, RBC and MCV did not significantly change in the groups treated with the tea extracts utilizing suppressive model of malaria treatment contrasted with the uninfected group and were comparable to those treated with chloroquine. Haemoglobin concentration nonetheless, varied significantly with respect to the uninfected group. Weight changes were most significant with 200 mg/kg bw of TD 570 treated group (32 % increase) on suppression. All in all, the green teas displayed high chemosuppressive and haematopoietic possibilities and are thusly prescribed as contender for additionally screening as elective antimalarial drugs

scholarly journals A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Andrea Hernández-Castañeda ◽  
Marilyne Lavergne ◽  
Pierina Casanova ◽  
Bryan Nydegger ◽  
Carla Merten ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Molecular Mechanisms ◽  
Γδ T Cells ◽  
Parasite Growth ◽  
Complex Life Cycle ◽  
Cholesterol Depletion ◽  
Host Cell Membrane ◽  
Pore Forming Proteins

Malaria remains one of the most serious health problems in developing countries. The causative agent of malaria, Plasmodium spp., have a complex life cycle involving multiple developmental stages as well as different morphological, biochemical and metabolic requirements. We recently found that γδ T cells control parasite growth using pore-forming proteins to deliver their cytotoxic proteases, the granzymes, into blood residing parasites. Here, we follow up on the molecular mechanisms of parasite growth inhibition by human pore-forming proteins. We confirm that Plasmodium falciparum infection efficiently depletes the red blood cells of cholesterol, which renders the parasite surrounding membranes susceptible to lysis by prokaryotic membrane disrupting proteins, such as lymphocytic granulysin or the human cathelicidin LL-37. Interestingly, not the cholesterol depletion but rather the simultaneous exposure of phosphatidylserine, a negatively charged phospholipid, triggers resistance of late stage parasitized red blood cells towards the eukaryotic pore forming protein perforin. Overall, by revealing the molecular events we establish here a pathogen-host interaction that involves host cell membrane remodeling that defines the susceptibility towards cytolytic molecules.

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