دورية أكاديمية
أعرض في EDS

The effect of memantine, an antagonist of the NMDA glutamate receptor, in in vitro and in vivo infections by Trypanosoma cruzi.

التفاصيل البيبلوغرافية
العنوان: The effect of memantine, an antagonist of the NMDA glutamate receptor, in in vitro and in vivo infections by Trypanosoma cruzi.
المؤلفون: Santos Souza HF; Laboratory of Biochemistry of Tryps-LaBTryps, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Rocha SC; Laboratory of Biochemistry of Tryps-LaBTryps, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Damasceno FS; Laboratory of Biochemistry of Tryps-LaBTryps, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Rapado LN; Laboratory of Biochemistry of Tryps-LaBTryps, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Pral EMF; Laboratory of Biochemistry of Tryps-LaBTryps, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Marinho CRF; Laboratory of Experimental Immunoparasitology, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Silber AM; Laboratory of Biochemistry of Tryps-LaBTryps, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
المصدر: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2019 Sep 19; Vol. 13 (9), pp. e0007226. Date of Electronic Publication: 2019 Sep 19 (Print Publication: 2019).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Chagas Disease/*drug therapy , Memantine/*pharmacology , Trypanocidal Agents/*pharmacology , Trypanosoma cruzi/*drug effects, Animals ; Calcium/metabolism ; Chagas Disease/parasitology ; Female ; Heart/parasitology ; Lipopolysaccharides/pharmacology ; Macrophages/parasitology ; Memantine/administration & dosage ; Mice ; Mice, Inbred BALB C ; Nitrogen Oxides/metabolism ; Parasite Load ; Parasitemia ; RAW 264.7 Cells ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Trypanocidal Agents/administration & dosage
مستخلص: Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease that affects 5-6 million people in endemic areas of the Americas. Presently, chemotherapy relies on two compounds that were proposed as trypanocidal drugs four decades ago: nifurtimox and benznidazole. Both drugs are able to eliminate parasitemia and to avoid seroconversion in infected people when used in the acute phase; however, their use in the chronic phase (the time when the majority of cases are diagnosed) is limited due to their serious side effects. Memantine is a glutamate receptor antagonist in the central nervous system of mammals that has been used for the treatment of Alzheimer's disease. Our group previously reported memantine as a trypanocidal drug that is able to induce apoptosis-like death in T. cruzi. In the present work, we further investigated the effects of memantine on the infection of RAW 264.7 macrophages and in vivo (in BALB/c mice). Here, we showed that memantine is able to diminish NO and Ca2+ entry in both LPS-activated and non-activated cells. These results, together with the fact that memantine was also able to reduce the infection of macrophages, led us to propose that this drug is able to activate a pro-oxidant non-NO-dependent cell defense mechanism. Finally, infected mice that were treated with memantine had diminished parasitemia, cardiac parasitic load, and inflammatory infiltrates. In addition, the treated mice had an increased survival rate. Taken together, these results indicate memantine to be a candidate drug for the treatment of Chagas disease.
Competing Interests: The authors have declared that no competing interests exist.
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معلومات مُعتمدة: MR/P027989/1 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (Lipopolysaccharides)
0 (Nitrogen Oxides)
0 (Receptors, N-Methyl-D-Aspartate)
0 (Trypanocidal Agents)
SY7Q814VUP (Calcium)
W8O17SJF3T (Memantine)
تواريخ الأحداث: Date Created: 20190920 Date Completed: 20200110 Latest Revision: 20210110
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC6752752
DOI: 10.1371/journal.pntd.0007226
PMID: 31536489
قاعدة البيانات: MEDLINE
الوصف
تدمد:1935-2735
DOI:10.1371/journal.pntd.0007226