<i>Plasmodium falciparum</i>Malaria: Reduction of Endothelial Cell Apoptosis In Vitro

Hemmer, Christoph Josef; Lehr, Hans A.; Westphal, Kathi; Unverricht, Marcus; Kratzius, Manja; Reisinger, Emil C.

doi:10.1128/iai.73.3.1764-1770.2005

Cited by 61 publications

(57 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30 Furthermore, as a mechanistic hint, the sequential analysis of proapoptotic and antiapoptotic gene expression in LPS/D-GalN-exposed liver has indicated that there is an early block in the transcription of antiapoptotic Bcl-2 and Bcl-X L after the LPS/D-GalN exposure, before the proapoptotic gene Bax is transcriptionally activated. 31 On the other hand, UTI reportedly reduces lymphocyte apoptosis, 32 although its mechanistic pathway remains unclear. In this study, apoptotic lesions in the liver were profoundly larger and more severe in UTI (À/À) than in WT mice in the presence of LPS/D-GalN.…”

Section: Uti In Liver Injury With Coagulatory Disturbancementioning

confidence: 99%

Urinary trypsin inhibitor protects against liver injury and coagulation pathway dysregulation induced by lipopolysaccharide/D-galactosamine in mice

Takano

Inoue

Shimada

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used for patients with inflammatory disorders including disseminated intravascular coagulation, shock, and pancreatitis in Japan. Our recent studies using UTI-null (À/À) mice have shown that UTI protects against systemic inflammatory responses and acute lung injury. However, the role of UTI in liver injury has not been elucidated. This study determined the contribution of UTI to liver injury and coagulatory disturbance induced by lipopolysaccharide and D-galactosamine (LPS/D-GalN) using UTI (À/À) and wild-type (WT) mice. LPS/D-GalN treatment caused severe liver injury characterized by neutrophilic inflammation, hemorrhagic change, necrosis, and apoptosis, which was more prominent in UTI (À/À) than in WT mice. In both genotypes of mice, LPS/D-GalN challenge caused elevations of aspartate amino-transferase and alanine amino-transferase, prolongation of the prothrombin and activated partial thromboplastin time, and decreases in fibrinogen and platelet counts, as compared with vehicle challenge. These changes, however, were significantly greater in UTI (À/À) than in WT mice. Circulatory levels of tumor necrosis factor (TNF)-a (Po0.05) and interferon (IFN)-g were also greater in UTI (À/À) than in WT mice after LPS/D-GalN challenge. These results suggest that UTI protects against severe liver injury and subsequent coagulatory disturbance induced by LPS/D-GalN, which was mediated, at least partly, through the suppression of TNF-a production along with its antiprotease activity.

show abstract

Section: Uti In Liver Injury With Coagulatory Disturbancementioning

confidence: 99%

Urinary trypsin inhibitor protects against liver injury and coagulation pathway dysregulation induced by lipopolysaccharide/D-galactosamine in mice

Takano

Inoue

Shimada

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Likewise, bioavailability of vasodilator nitric oxide (NO), which may be impaired in human and in experimental malaria, could potentially aggravate inflammation-related events through enhanced expression of adhesion molecules and the exarcebation of cytoadherence and [13][14][15][16] . In support of a decompensated state in severe malaria are findings of EC apoptosis 42 , identification of circulating microparticles 21,46 , and accumulation of platelets and monocytes in the vessels of the brain 39 from CM cases but not from uncomplicated malaria. It is important to recognize that compensated states occur in baboons infected with escalating doses of Escherichia coli 27,40 , an experimental model for sepsis.…”

Section: The Tissue Factor Model For Malaria Pathogenesismentioning

confidence: 99%

“…The TFM also takes into account events potentially associated with sequestration such as hypoxia [1][2][3] , fibrin formation* 20 , apoptosis 42 , and cytokine production [1][2][3]11 which may contribute to the procoagulant/inflammatory tonus observed in the disease. Likewise, molecules from pRBC (e.g.…”

Section: The Tissue Factor Model For Malaria Pathogenesismentioning

confidence: 99%

Does activation of the blood coagulation cascade have a role in malaria pathogenesis?

Francischetti

2008

Trends in Parasitology

View full text Add to dashboard Cite

Plasmodium falciparum infection is often associated with a procoagulant state. Recent identification of tissue factor (TF) in the brain endothelium of patients who died from cerebral malaria casts new light in our understanding of the coagulation disorder found in P. falciparum infection. It has also been revealed that parasitized red blood cells (pRBC) support assembly of multimolecular coagulation complexes. In this article, the role of TF expression by the endothelium and amplification of the coagulation cascade by pRBC and/or activated platelets-particularly at sequestration sitesis discussed as crucial events in mounting and sustaining a coagulation-inflammation cycle that contributes to organ dysfunction and coma in P. falciparum malaria. Blood coagulation and malariaMalaria caused by P. falciparum remains a highly endemic disease; it has been estimated that at least one million deaths occur every year. Children are at high risk, and often severe malaria (severe anemia or cerebral malaria [CM]) is the cause of death in this population 1-4. P. falciparum infection is associated with sequestration 5 -8 , endothelial cell (EC) activation 8-10, increase in inflammatory cytokines 3 , 11, and activation of the coagulation cascade 12 -20. Despite several papers devoted to the coagulation disorder in malaria-many of them published during the 1970s and 1980s (reviewed in Ref. 20)-the mechanism that triggers and propagates the coagulation activation in P. falciparum infection has remained elusive. These studies, however, demonstrated that bleeding and/or hemorrhage are typically not present, although laboratory tests indicate a certain degree of in vivo blood coagulation activation 12 -20 . Accordingly, prothrombin time (PT) and partial thromboplastin time (PTT) are close to normal values or prolonged, whereas thrombin-antithrombin complex (TAT) (which indicates in vivo thrombin formation) and D-dimers (which are a marker of in vivo fibrinolysis) are often elevated, and thrombocytopenia is a usual finding 12 -21 . This laboratory profile is compatible with disseminated intravascular coagulation (DIC), which is diagnosed according to a score defined by the International Society of Thrombosis and Haemostasis (ISTH) 22 . The scoring system takes into account i) platelet count, ii) elevated fibrin related markers, iii) prolonged prothrombin time, and iv) fibrinogen level 22 23 . Depending on the score punctuation, levels < 5 are suggestive of non-overt (compensated) DIC while scores > or = 5 are compatible with overt (decompensated) DIC. Bleeding is more common in overt DIC, but it is not needed for the formal diagnosis 22 23. In other words, absence of bleeding in P. falciparum-infected patients does not exclude the presence of DIC in this same population; actually, most of these patients meet the criteria for DIC as defined above 22 . Unfortunately, absence of bleeding is often mistakenly regarded as the reason why DIC is supposedly not present in malaria. Further, some reports do not support the view that coa...

show abstract

“…37 It has also been observed that apoptosis of endothelial cells caused by severe malaria could be reduced by antioxidants. 38,39 Furthermore, the flavonoid quercetin is reported to be capable of preventing hepatotoxicity caused by oxidative damage. 27,28 Following from these, it is postulated that in the current study, components in ingested natural cocoa exerted anti-inflammatory and antioxidative properties that blunted the damage caused to hepatic sinusoids by ROS, oxidative stress, and immune-responsive proinflammatory factors engendered by P. berghei infection.…”

Section: Discussionmentioning

confidence: 99%

Natural cocoa ingestion reduced liver damage in mice infected with Plasmodium berghei (NK65)

Aidoo¹,

Addai²,

Ahenkorah³

et al. 2012

RRTM

View full text Add to dashboard Cite

Purpose: This study tested whether natural cocoa powder ingestion could mitigate hepatic injury coincident with murine malaria. Plasmodium berghei infection causes liver damage including hepatic sinusoidal distension, and elevated serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. According to literature, these pathologies largely result from activity of reactive oxygen species (ROS) and may be extenuated by antioxidants. Animals and methods: Thirty Balb/c mice were randomly assigned to three equal groups. One of two groups of mice inoculated with 0.2 mL of P. berghei-parasitized red blood cells (RBCs) was given unrestricted 24-hour access to a natural cocoa powder beverage (2% by weight) in place of water. The third group of mice were neither infected nor given cocoa. All mice were fed the same standard chow. After 6 days, mice were sacrificed and their livers processed for histomorphometric assessment of mean hepatic sinusoidal diameter as a quantitative measure of altered morphology. Serum ALT and AST were measured as a gauge of functional impairment. Results: Compared with uninfected mice, hepatic sinusoidal diameter in P. berghei-infected mice not given cocoa increased by 150%, whereas a smaller increase of 83% occurred in infected mice that ingested cocoa. Mean serum ALT increased by 127% in infected mice not given cocoa and 80% in infected mice that consumed cocoa, compared with the value for uninfected mice. Similarly, mean serum AST was raised by 141% in infected mice not given cocoa and 93% in infected mice that drank cocoa. Conclusion: Distension of hepatic sinusoidal diameter in P. berghei-infected mice was reduced by 67%, whereas respective elevations of serum ALT and AST concentrations were reduced by 47% and 48% via ingestion of cocoa. Anti-inflammatory and antioxidant components of cocoa probably mediated the demonstrated hepatoprotective benefit by blunting pernicious ROS activity in P. berghei-infected mice.

show abstract

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Cited by 61 publications

References 52 publications

Urinary trypsin inhibitor protects against liver injury and coagulation pathway dysregulation induced by lipopolysaccharide/D-galactosamine in mice

Urinary trypsin inhibitor protects against liver injury and coagulation pathway dysregulation induced by lipopolysaccharide/D-galactosamine in mice

Does activation of the blood coagulation cascade have a role in malaria pathogenesis?

Natural cocoa ingestion reduced liver damage in mice infected with Plasmodium berghei (NK65)

Contact Info

Product

Resources

About