Effects of Highly Diluted Drugs on Experimental Infection with Trypanosoma cruzi In Vivo: Systematic Review

2020 ◽  
Vol 26 (10) ◽  
pp. 866-883
Author(s):  
Daniela Cristina Grégio d'Arce Mota ◽  
Érika Cristina Ferreira ◽  
Fabiana Nabarro Ferraz ◽  
Maria Vitória Felipe de Souza ◽  
Bruna Lauton Simões ◽  
...  
Author(s):  
Nadjania Saraiva de Lira Silva ◽  
Cristina Mary Orikaza ◽  
Fabiana Rodrigues de Santana ◽  
Luana Aguiar dos Santos ◽  
Bruno Ramos Salu ◽  
...  

Chagas’ disease is a parasitosis caused by Trypanosoma cruzi, which affects approximately 8 million people worldwide. The balance between pro- and anti-inflammatory cytokines produced during immunological responses contributes to disease prognosis and progression. Parasite tissue persistence can induce chronic inflammatory stimuli, which can cause long-term tissue injury and fibrosis. Chronic Chagas’ patients exhibit increased levels of interleukin (IL)-9, an important cytokine in the regulation of inflammatory and fibrogenic processes. Data on the role of IL-9 in other pathologies are sometimes contradictory, and few studies have explored this cytokine’s influence in Chagas’ disease pathology. Hence, the aim of this study was to evaluate the role of IL-9 in the progression of T. cruzi infection in vivo and in vitro. In vitro infection demonstrated that IL-9 reduced the number of infected cells and decreased the multiplication of intracellular amastigotes in both C2C12 myoblasts and bone marrow-derived macrophages. In myoblasts, the increased production of nitric oxide (NO) was essential for reduced parasite multiplication, whereas macrophage responses resulted in increased IL-6 and reduced TGF-β levels, indicating that parasite growth restriction mechanisms induced by IL-9 were cell-type specific. Experimental infection of BALB/c mice with T. cruzi trypomastigotes of the Y strain implicated a major role of IL-9 during the chronic phase, as increased Th9 and Tc9 cells were detected among splenocytes; higher levels of IL-9 in these cell populations and increased cardiac IL-9 levels were detected compared to those of uninfected mice. Moreover, rIL9 treatment decreased serum IL-12, IL-6, and IL-10 levels and cardiac TNF-α levels, possibly attempting to control the inflammatory response. IL-9 neutralization increased cardiac fibrosis, synthesis of collagens I and III, and mastocyte recruitment in BALB/c heart tissue during the chronic phase. In conclusion, our data showed that IL-9 reduced the invasion and multiplication of T. cruzi in vitro, in both myoblasts and macrophages, favoring disease control through cell-specific mechanisms. In vivo, IL-9 was elevated during experimental chronic infection in BALB/c mice, and this cytokine played a protective role in the immunopathological response during this phase by controlling cardiac fibrosis and proinflammatory cytokine production.


2021 ◽  
Vol 13 (47) ◽  
pp. 108-110
Author(s):  
Angela Rigo Portocarrero ◽  
Patrícia Flora Sandri ◽  
Franciele Karina Da Veiga ◽  
Larissa Ciupa ◽  
Fabiana Nabarro Ferraz ◽  
...  

Background: In experiments with homeopathic medicines is important to test the inert vehicle from succussed preparations for the treatment control. Aim: To evaluate the effect of hydro-alcoholic solutions 1cH, 6cH and 30cH in mice’s experimental infection with Trypanosoma cruzi. Methodology: In a blind, randomized, controlled test, two independent experiments with 34 and 51 swiss male mice, 8 weeks old, kept in cages micro acclimated, infected with 1400 blood trypomastigotes of the Y strain of T. cruzi (via IP), were divided: IC-untreated control; G1cH-received hydro-alcoholic solution dynamized 1cH; G6cH-received hydro-alcoholic solution dynamized 6cH and G30cH-received hydro-alcoholic solution dynamized 30cH. The solutions were prepared according to Brazilian Homeophatic Pharmacopoeia1 with alcohol 70 ° GL. Final preparations (1cH, 6cH and 30cH) were manipulated with water (Sigma-SP-Brazil). The treatment was offered diluted with water (1/100mL) ad libitum 48 hours before infection, available for 16h. After infection, the animals were treated 56h/56h for 16h until the 9th day of infection. The parasitological parameters were analyzed: Curve of Parasitemia, Total Parasitemia (TP), Peak Maximum of Parasites (PMP), Pre-Patent Period (PPP), Patent Period (PP) and Survival. The experiment was approved by the UEM’s Ethical Committee. Results: G1cH showed a higher survival (p=0.044) with a life expectancy of 2.58 times larger than the control group (Figure 1.A), as well as lower TP (p=0.002) and PMP (p = 0.018). PPP and PP showed no statistical difference, although in G1cH1 it was observed an increasing trend of PPP (p=0.065). These results are related to host’s benefit. The G6cH group presented a longer survival (p=0,045), with a life expectancy 1.94 times larger than the control group (Figure 1.B). Although no difference to TP, PMP, PP and PPP has been observed, the alcohol 6cH performed protecting animals against infection. The G30cH displayed an increasing trend of PMP (p=0.066) compared to the control group. Effects of inert vehicle succussed have been reported in studies in vitro2. However, no effects had been reported in vivo studies yet2,3. The hydro-alcoholic solution 7% 13CH, tested under the same conditions and animal model, did not change the natural evolution of the infection2. Conclusion: The hydro-alcoholic solutions 1cH and 6cH altered the course of experimental infection by T. cruzi, reducing the parasitemia and/or increasing the survival time, and can not be considered as inert vehicle in the high diluted compounds preparation.


2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Andréa Aparecida Santos Mendonça ◽  
Camila Morais Coelho ◽  
Marcia Paranho Veloso ◽  
Ivo Santana Caldas ◽  
Reggiani Vilela Gonçalves ◽  
...  

Due to the rudimentary antioxidant defenses in Trypanosoma cruzi, disruptors of redox balance are promising candidates for new antitrypanosomal drugs. We developed an integrated model based on systematic review, meta-analyses, and molecular modeling to evaluate the effect of trypanothione reductase (TR) inhibitors in T. cruzi infections. Our findings indicated that the TR inhibitors analyzed were effective in reducing parasitemia and mortality due to Trypanosoma cruzi infection in animal models. The most investigated drugs (clomipramine and thioridazine) showed no beneficial effects on the occurrence of infection-related electrocardiographic abnormalities or the affinity and density of cardiac β-adrenergic receptors. The affinity between the tested ligands and the active site of TR was confirmed by molecular docking. However, the molecular affinity score was unable to explain TR inhibition and T. cruzi death in vitro or the antiparasitic potential of these drugs when tested in preclinical models of T. cruzi infection. The divergence of in silico, in vitro, and in vivo findings indicated that the anti-T. cruzi effects of the analyzed drugs were not restricted to TR inhibition. As in vivo studies on TR inhibitors are still scarce and exhibit methodological limitations, mechanistic and highly controlled studies are required to improve the quality of evidence.


Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
C Quitino-da-Rocha ◽  
E Ferreira-Queiroz ◽  
C Santana-Meira ◽  
DR Magalhães-Moreira ◽  
M Botelho-Pereira-Soares ◽  
...  
Keyword(s):  

2019 ◽  
Vol 14 (6) ◽  
pp. 504-518 ◽  
Author(s):  
Dilcele Silva Moreira Dziedzic ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira ◽  
Ana Carolina Irioda ◽  
Katherine Athayde Teixeira de Carvalho

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.


2018 ◽  
Vol 18 (7) ◽  
pp. 985-992 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Ertan Kucuksayan ◽  
Rana Cagla Akduman ◽  
Tomris Ozben

This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.


2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.


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