Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi mathvariant="bold">κ</mml:mi></mml:mrow></mml:math>B Translocation in a Mechanism Independent of Plasmodium Killing

Souza, Mariana C.; Paixao, F.; Ferraris, F; Ribeiro, Isabela; Henriques, Maria das Graças

doi:10.1155/2012/679090

Cited by 16 publications

(20 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Histologically, brains from mice with ECM exhibit cortical edema, congested capillaries, increased numbers of microglial cells, and glial cell swelling [ 26 – 28 ]. In addition, Nacer et al [ 29 ] proposed recently that intracranial hypertension plays a crucial role in ECM development.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria

et al. 2015

View full text Add to dashboard Cite

IntroductionMalaria is the most relevant parasitic disease worldwide, and still accounts for 1 million deaths each year. Since current antimalarial drugs are unable to prevent death in severe cases, new therapeutic strategies have been developed. Mesenchymal stromal cells (MSC) confer host resistance against malaria; however, thus far, no study has evaluated the therapeutic effects of MSC therapy on brain and distal organ damage in experimental cerebral malaria.MethodsForty C57BL/6 mice were injected intraperitoneally with 5 × 106Plasmodium berghei-infected erythrocytes or saline. After 24 h, mice received saline or bone marrow (BM)-derived MSC (1x105) intravenously and were housed individually in metabolic cages. After 4 days, lung and kidney morphofunction; cerebrum, spleen, and liver histology; and markers associated with inflammation, fibrogenesis, and epithelial and endothelial cell damage in lung tissue were analyzed.ResultsIn P. berghei-infected mice, BM-MSCs: 1) reduced parasitemia and mortality; 2) increased phagocytic neutrophil content in brain, even though BM-MSCs did not affect the inflammatory process; 3) decreased malaria pigment detection in spleen, liver, and kidney; 4) reduced hepatocyte derangement, with an increased number of Kupffer cells; 5) decreased kidney damage, without effecting significant changes in serum creatinine levels or urinary flow; and 6) reduced neutrophil infiltration, interstitial edema, number of myofibroblasts within interstitial tissue, and collagen deposition in lungs, resulting in decreased lung static elastance. These morphological and functional changes were not associated with changes in levels of tumor necrosis factor-α, keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8), or interferon-γ, which remained increased and similar to those of P. berghei animals treated with saline. BM-MSCs increased hepatocyte growth factor but decreased VEGF in the P. berghei group.ConclusionsBM-MSC treatment increased survival and reduced parasitemia and malaria pigment accumulation in spleen, liver, kidney, and lung, but not in brain. The two main organs associated with worse prognosis in malaria, lung and kidney, sustained less histological damage after BM-MSC therapy, with a more pronounced improvement in lung function.

show abstract

Section: Discussionmentioning

confidence: 99%

Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Monoclonal antibodies against ICAM-1 could attenuate cerebral vasospasm by 22% after SAH in rabbits [39]. As anti-ICAM-1 antibody, artesunate could inhibit the expression of ICAM-1 in order to resist the P. berghei -induced inflammatory response [40]. It implied that artesunate probably also had the effect of inhibiting the expression of ICAM-1 after SAH.…”

Section: Effect Of Artesunate On Central Nervous System Diseasesmentioning

confidence: 99%

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Zuo

Liu

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

Artesunate is an important agent for cerebral malaria and all kinds of other severe malaria because it is highly efficient, lowly toxic, and well-tolerated. Loads of research pointed out that it had widespread pharmacological activities such as antiparasites, antitumor, anti-inflammation, antimicrobes activities. As we know, the occurrence and development of neurological disorders usually refer to intricate pathophysiologic mechanisms and multiple etiopathogenesis. Recent progress has also demonstrated that drugs with single mechanism and serious side-effects are not likely the candidates for treatment of the neurological disorders. Therefore, the pluripotent action of artesunate may result in it playing an important role in the prevention and treatment of these neurological disorders. This review provides an overview of primary pharmacological mechanism of artesunate and its potential therapeutic effects on neurological disorders. Meanwhile, we also briefly summarize the primary mechanisms of artemisinin and its derivatives. We hope that, with the evidence presented in this review, the effect of artesunate in prevention and curing for neurological disorders can be further explored and studied in the foreseeable future.

show abstract

“…It is worth noting that the most important class of antimalarial drug to treat severe malaria is artemisinin and its derivatives [ 78 ], which also have immunomodulatory activities in pathologies such as microbial infections, tumor growth, and inflammatory diseases [ 79 – 82 ]. Our group demonstrated that, in addition to its antimalarial properties, artesunate exerted a protective effect against severe malaria via its immunomodulatory properties by inhibiting endothelial cell activation, NF- κ B nuclear translocation, and the subsequent expression of ICAM-1 [ 83 ].…”

Section: Leukocyte/endothelium Interaction During Malaria As a Tarmentioning

confidence: 99%

Endothelial‐Leukocyte Interaction in Severe Malaria: Beyond the Brain

Souza

Pádua

Henriques

2015

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

Malaria is the most important parasitic disease worldwide, accounting for 1 million deaths each year. Severe malaria is a systemic illness characterized by dysfunction of brain tissue and of one or more peripheral organs as lungs and kidney. The most severe and most studied form of malaria is associated with cerebral complications due to capillary congestion and the adhesion of infected erythrocytes, platelets, and leukocytes to brain vasculature. Thus, leukocyte rolling and adhesion in the brain vascular bed during severe malaria is singular and distinct from other models of inflammation. The leukocyte/endothelium interaction and neutrophil accumulation are also observed in the lungs. However, lung interactions differ from brain interactions, likely due to differences in the blood-brain barrier and blood-air barrier tight junction composition of the brain and lung endothelium. Here, we review the importance of endothelial dysfunction and the mechanism of leukocyte/endothelium interaction during severe malaria. Furthermore, we hypothesize a possible use of adjunctive therapies to antimalarial drugs that target the interaction between the leukocytes and the endothelium.

show abstract

Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF-κB Translocation in a Mechanism Independent of Plasmodium Killing

Cited by 16 publications

References 42 publications

Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria

Mesenchymal stromal cell therapy attenuated lung and kidney injury but not brain damage in experimental cerebral malaria

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Endothelial‐Leukocyte Interaction in Severe Malaria: Beyond the Brain

Contact Info

Product

Resources

About