Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine<i>Trypanosoma cruzi</i>infection

Tatakihara, Vera Lúcia Hideko; Cecchini, Rúbens; Borges, Celso Luiz; Malvezi, Aparecida Donizette; Souza, Viviane Krominski Graça-de; Yamada‐Ogatta, Sueli Fumie; Rizzo, Luiz Vicente; Pinge‐Filho, Phileno

doi:10.1111/j.1574-695x.2007.00340.x

Cited by 57 publications

(67 citation statements)

References 50 publications

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“…Previous studies have shown that the release of eicosanoids during infection with T. cruzi regulates host responses and controls disease progression (10,(27)(28)(29)(30)(31). PGs, together with NO and TNF-␣, participate in a complex circuit that controls lymphoproliferative and cytokine responses in T. cruzi infection (28).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Cyclooxygenase-1 and Cyclooxygenase-2 Impairs Trypanosoma cruzi Entry into Cardiac Cells and Promotes Differential Modulation of the Inflammatory Response

Malvezi

Silva

Freitas

et al. 2014

Antimicrob Agents Chemother

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fThe intracellular protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite's life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host's cyclooxygenase (COX) enzymes during T. cruzi invasion. Pharmacological antagonists for COX-1 (aspirin) and COX-2 (celecoxib) caused marked inhibition of T. cruzi infection when rat cardiac cells were pretreated with these nonsteroidal anti-inflammatory drugs (NSAIDs) for 60 min at 37°C before inoculation. This inhibition was associated with an increase in the production of NO and interleukin-1␤ and decreased production of transforming growth factor ␤ (TGF-␤) by cells. Taken together, these results indicate that COX-1 more than COX-2 is involved in the regulation of anti-T. cruzi activity in cardiac cells, and they provide a better understanding of the influence of TGF-␤-interfering therapies on the innate inflammatory response to T. cruzi infection and may represent a very pertinent target for new therapeutic treatments of Chagas disease.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Cyclooxygenase-1 and Cyclooxygenase-2 Impairs Trypanosoma cruzi Entry into Cardiac Cells and Promotes Differential Modulation of the Inflammatory Response

Malvezi

Silva

Freitas

et al. 2014

Antimicrob Agents Chemother

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“…Trypanosoma cruzi 118 , as well as for human rhinoviruses 119 infections in mice. In some cases, however, this does not appear to be the case, as illustrated for the therapeutic effect exerted by the cyclooxygenase inhibitor ibuprofen against Mycobacterium tuberculosis infection in mice 116 .…”

Section: Pharmacological Modulation Of Disease Tolerancementioning

confidence: 99%

Disease tolerance and immunity in host protection against infection

2017

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The immune system has most likely evolved to limit the negative impact exerted by pathogens on host homeostasis. This defense strategy relies on the concerted action of innate and adaptive components of the immune system, which sense and target pathogens for containment, destruction or expulsion. Resistance to infection refers to these immune functions, which reduce the pathogen load of an infected host as the means to preserve homeostasis. Immune-driven resistance to infection is coupled to an additional, and arguably as important, defense strategy that limits the extent of dysfunction imposed to host parenchyma tissues during infection, without exerting a direct negative impact on pathogens.This defense strategy, called disease tolerance, relies on tissue damage control mechanisms that prevent the deleterious effects of pathogens, while uncoupling immunedriven resistance mechanisms from immunopathology and disease. Here we provide a unifying view of resistance and disease tolerance within the framework of immunity to infection.

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“…Prostaglandin synthesis during T. cruzi infection is related to nitric oxide production (Durand et al, 2009;Ganzinelli et al, 2009). At least two mechanisms of oxidative stress exists, dependent or independent, with regard to the nitric oxide and cyclooxygenase pathway, where one or the other is more evident depending on the cell type or mouse strain (Freirede-Lima et al, 2006;Ganzinelli et al, 2009;Hideko Tatakihara et al, 2008;Silva et al, 2003). Phagocytosis of apoptotic bodies from T-lymphocytes or neutrophils, produced by the action of TNF-α , generated in macrophages infected with T. cruzi, induces the production of TGF-β and prostaglandin.…”

Section: Role Of Prostaglandins In the Pathogenesis Of Chagas Diseasementioning

confidence: 99%

“…Accordingly, the content of NO in the macrophage decreases, and the parasite proliferates (DosReis and Lopes, 2009a;Freire-deLima et al, 2000;Lopes and DosReis, 2000). On the other hand, high levels of PGE2 are produced by macrophages (Abdalla et al, 2008) and spleen cells from T. cruziinfected mice and the inhibition of cyclooxygenase by indomethacin resulted in marked reduction of PGE2 (Hideko Tatakihara et al, 2008;Pinge-Filho et al, 1999). During early infection, treatment with aspirin or indomethacin increased parasitemia dramatically and reduced the survival rate of T. cruzi-infected C57BL/6 or C3H/HeN mice, which are characteristically resistant to acute infection (Celentano et al, 1995).…”

Section: Role Of Prostaglandins In the Pathogenesis Of Chagas Diseasementioning

confidence: 99%

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

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There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

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Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murineTrypanosoma cruziinfection

Cited by 57 publications

References 50 publications

Inhibition of Cyclooxygenase-1 and Cyclooxygenase-2 Impairs Trypanosoma cruzi Entry into Cardiac Cells and Promotes Differential Modulation of the Inflammatory Response

Inhibition of Cyclooxygenase-1 and Cyclooxygenase-2 Impairs Trypanosoma cruzi Entry into Cardiac Cells and Promotes Differential Modulation of the Inflammatory Response

Disease tolerance and immunity in host protection against infection

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

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