Dual chemotherapy with benznidazole at suboptimal dose plus curcumin nanoparticles mitigates Trypanosoma cruzi-elicited chronic cardiomyopathy

Hernández, Matías; Wicz, Susana; Caballero, Eugenia Pérez; Santamaría, Miguel H.; Corral, Ricardo S.

doi:10.1016/j.parint.2020.102248

Cited by 13 publications

(28 citation statements)

References 47 publications

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“…The tissue collagen deposition was decreased in CUR, and was not changed with BZN, but it was more effective when used in combination with the latter drug. These results are very consistent in showing the cardiac benefits of CUR plus BZN [ 96 ].…”

Section: Discussionsupporting

confidence: 77%

“…Five reports were included involving CUR treatment and most of them carried out in vivo and in vitro experiments [ 92 , 93 , 94 , 95 , 96 ]. We collected only the in vivo results.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the poor solubility of CUR that hinders the bioavailability and the lack of drugs for the chronic phase of CD, Hernandez et al, in 2021 [ 96 ], conducted the experiment in the chronic phase with 200 mg/kg of CUR nanoparticules (nano-CUR) for 30 days, starting at 60 dpi, comparing with BZN in a suboptimal dose (25 mg/kg), at 130 dpi. The survival level was not reported and the parasitemia load was detected only in the myocardium, which was shown to be 4.39-fold higher in infected animals and nano-CUR, compared to those treated by BZN, suggesting that nano-CUR has no antiparasitic activity.…”

Section: Discussionmentioning

confidence: 99%

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Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Imperador¹,

Scarim

Bosquesi

et al. 2022

Pharmaceuticals

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Chagas disease (CD) is a neglected protozoan infection caused by Trypanosoma cruzi, which affects about 7 million people worldwide. There are two available drugs in therapeutics, however, they lack effectiveness for the chronic stage—characterized mainly by cardiac (i.e., cardiomyopathy) and digestive manifestations (i.e., megaesophagus, megacolon). Due to the involvement of the immuno-inflammatory pathways in the disease’s progress, compounds exhibiting antioxidant and anti-inflammatory activity seem to be effective for controlling some clinical manifestations, mainly in the chronic phase. Resveratrol (RVT) and curcumin (CUR) are natural compounds with potent antioxidant and anti-inflammatory properties and their cardioprotective effect have been proposed to have benefits to treat CD. Such effects could decrease or block the progression of the disease’s severity. The purpose of this systematic review is to analyze the effectiveness of RVT and CUR in animal and clinical research for the treatment of CD. The study was performed according to PRISMA guidelines and it was registered on PROSPERO (CDR42021293495). The results did not find any clinical study, and the animal research was analyzed according to the SYRCLES risk of bias tools and ARRIVE 2.0 guidelines. We found 9 eligible reports in this study. We also discuss the potential RVT and CUR derivatives for the treatment of CD as well.

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Section: Discussionsupporting

confidence: 77%

“…Five reports were included involving CUR treatment and most of them carried out in vivo and in vitro experiments [ 92 , 93 , 94 , 95 , 96 ]. We collected only the in vivo results.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Imperador¹,

Scarim

Bosquesi

et al. 2022

Pharmaceuticals

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“…By killing the parasite subsequently reducing parasite load, the availability of antigen to maintain the T. cruzi -specific effector T cells also diminishes, therefore, causing a rearrangement in Th1-driven immunological response contributing to a more regulatory milieu in humans ( Albareda and Laucella, 2015 ). Previous studies aimed to explore the suboptimal dose of Bz alone or in combination with other drugs ( Strauss et al., 2013 ; Khare et al., 2015 ; Francisco et al., 2016 ; Hernández et al., 2021 ; Martins and Sampaio, 2021 ), and it has been shown that it is effective in decreasing parasite load, attenuating inflammation in the cardiac tissue, and reducing pro-inflammatory cytokines in T. cruzi -infected mice and cultured cardiomyocytes ( Cevey et al., 2016 ). Apart from all the modulated immune genes following Bz treatment, another notable finding was the increase in the production of IL-10 by two-fold compared with the vehicle-treated group.…”

Section: Discussionmentioning

confidence: 99%

Treatment With Suboptimal Dose of Benznidazole Mitigates Immune Response Molecular Pathways in Mice With Chronic Chagas Cardiomyopathy

Farani

Begum

Vilar-Pereira

et al. 2021

Front. Cell. Infect. Microbiol.

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Chronic Chagas cardiomyopathy (CCC) is the most frequent and severe form of Chagas disease, a neglected tropical illness caused by the protozoan Trypanosoma cruzi, and the main cause of morbimortality from cardiovascular problems in endemic areas. Although efforts have been made to understand the signaling pathways and molecular mechanisms underlying CCC, the immunological signaling pathways regulated by the etiological treatment with benznidazole (Bz) has not been reported. In experimental CCC, Bz combined with the hemorheological and immunoregulatory agent pentoxifylline (PTX) has beneficial effects on CCC. To explore the molecular mechanisms of Bz or Bz+PTX therapeutic strategies, C57BL/6 mice chronically infected with the T. cruzi Colombian strain (discrete typing unit TcI) and showing electrocardiographic abnormalities were submitted to suboptimal dose of Bz or Bz+PTX from 120 to 150 days postinfection. Electrocardiographic alterations, such as prolonged corrected QT interval and heart parasite load, were beneficially impacted by Bz and Bz+PTX. RT-qPCR TaqMan array was used to evaluate the expression of 92 genes related to the immune response in RNA extracted from heart tissues. In comparison with non-infected mice, 30 genes were upregulated, and 31 were downregulated in infected mice. Particularly, infection upregulated the cytokines IFN-γ, IL-12b, and IL-2 (126-, 44-, and 18-fold change, respectively) and the T-cell chemoattractants CCL3 and CCL5 (23- and 16-fold change, respectively). Bz therapy restored the expression of genes related to inflammatory response, cellular development, growth, and proliferation, and tissue development pathways, most probably linked to the cardiac remodeling processes inherent to CCC, thus mitigating the Th1-driven response found in vehicle-treated infected mice. The combined Bz+PTX therapy revealed pathways related to the modulation of cell death and survival, and organismal survival, supporting that this strategy may mitigate the progression of CCC. Altogether, our results contribute to the better understanding of the molecular mechanisms of the immune response in the heart tissue in chronic Chagas disease and reinforce that parasite persistence and dysregulated immune response underpin CCC severity. Therefore, Bz and Bz+PTX chemotherapies emerge as tools to interfere in these pathways aiming to improve CCC prognosis.

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“…The co-administration of CUR-PLGA-NPs and free BNZ resulted in improved trypanocidal activity and a decrease in the pro-inflammatory response, reducing heart fibrosis and cardiac hypertrophy. These findings revealed that molecules that suppress the release of inflammatory mediators should be explored in combination with antiparasitic drugs to treat chagasic inflammation and chronic parasitosis simultaneously (Hernandez et al, 2021).…”

Section: American Trypanosomiasis: Chagas Diseasementioning

confidence: 99%

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

Scariot

Staneviciute

Zhu

et al. 2022

Front. Cell. Infect. Microbiol.

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Nanotechnology is revolutionizing many sectors of science, from food preservation to healthcare to energy applications. Since 1995, when the first nanomedicines started being commercialized, drug developers have relied on nanotechnology to improve the pharmacokinetic properties of bioactive molecules. The development of advanced nanomaterials has greatly enhanced drug discovery through improved pharmacotherapeutic effects and reduction of toxicity and side effects. Therefore, highly toxic treatments such as cancer chemotherapy, have benefited from nanotechnology. Considering the toxicity of the few therapeutic options to treat neglected tropical diseases, such as leishmaniasis and Chagas disease, nanotechnology has also been explored as a potential innovation to treat these diseases. However, despite the significant research progress over the years, the benefits of nanotechnology for both diseases are still limited to preliminary animal studies, raising the question about the clinical utility of nanomedicines in this field. From this perspective, this review aims to discuss recent nanotechnological developments, the advantages of nanoformulations over current leishmanicidal and trypanocidal drugs, limitations of nano-based drugs, and research gaps that still must be filled to make these novel drug delivery systems a reality for leishmaniasis and Chagas disease treatment.

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Dual chemotherapy with benznidazole at suboptimal dose plus curcumin nanoparticles mitigates Trypanosoma cruzi-elicited chronic cardiomyopathy

Cited by 13 publications

References 47 publications

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Resveratrol and Curcumin for Chagas Disease Treatment—A Systematic Review

Treatment With Suboptimal Dose of Benznidazole Mitigates Immune Response Molecular Pathways in Mice With Chronic Chagas Cardiomyopathy

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

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