Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão / G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.

Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

ANRIL, H19 and TUG1: a review about critical long non-coding RNAs in cardiovascular diseases.

Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.

Discovery of a new dihydroeugenol-chalcone hybrid with cytotoxic and anti-migratory potential: A dual-action hit for cancer therapeutics.

Cancer still represents a serious public health problem and one of the main problems related to the worsening of this disease is the ability of some tumors to develop metastasis. In this work, we synthesized a new series of chalcones and isoxazoles derived from eugenol and analogues as molecular hybrids and these compounds were evaluated against different tumor cell lines. This structural pattern was designed considering the cytotoxic potential already known for eugenol, chalcones and isoxazoles. Notably, chalcones 7, 9, 10, and 11 displayed significant activity (4.2-14.5 µM) against two cancer cell lines, surpassing the potency of the control drug doxorubicin. The reaction of chalcones with hydroxylamine hydrochloride provided the corresponding isoxazoles that were inactive against these cancer cells. The dihydroeugenol chalcone 7 showed the most promising results, demonstrating higher potency against HepG2 (CC50: 4.2 µM) and TOV-21G (CC50: 7.2 µM). Chalcone 7 was also three times less toxic than doxorubicin considering HepG2 cells, with a selectivity index greater than 11. Further investigations including clonogenic survival, cell cycle progression and cell migration assays confirmed the compelling antitumoral potential of chalcone 7, as it reduced long-term survival due to DNA fragmentation, inducing cell death and inhibiting HepG2 cells migration. Moreover, in silico studies involving docking and molecular dynamics revealed a consistent binding mode of chalcone 7 with metalloproteinases, particularly MMP-9, shedding light on its potential mechanism of action related to anti-migratory effects. These significant findings suggest the inclusion of compound 7 as a promising candidate for future studies in the field of cancer therapeutics.

Cytotoxic effect of crotoxin on cancer cells and its antitumoral effects correlated to tumor microenvironment: A review.

Cancer is the second leading cause of death worldwide, and despite the effort of standard treatments, the search for new tools against this disease is necessary. Importantly, it is known that the tumor microenvironment plays a crucial role in tumor initiation, progression, and response to therapies. Therefore, studies of potential drugs that act on these components are as critical as studies regarding antiproliferative substances. Through the years, studies of several natural products, including animal toxins, have been conducted to guide the development of medical compounds. In this review, we present the remarkable antitumor activities of crotoxin, a toxin from the rattlesnake Crotalus durissus terrificus, highlighting its effects on cancer cells and in the modulation of relevant elements in the tumor microenvironment as well as the clinical trials conducted with this compound. In summary, crotoxin acts through several mechanisms of action, such as activation of apoptosis, induction of cell cycle arrest, inhibition of metastasis, and decrease of tumor growth, in different tumor types. Crotoxin also modulates tumor-associated fibroblasts, endothelial cells, and immune cells, which contribute to its antitumoral effects. In addition, preliminary clinical studies confirm the promising results of crotoxin and support its potential future use as an anticancer drug.

LncRNA JHDM1D-AS1 Is a Key Biomarker for Progression and Modulation of Gemcitabine Sensitivity in Bladder Cancer Cells.

Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.

Resveratrol induces the production of reactive oxygen species, interferes with the cell cycle, and inhibits the cell migration of bladder tumour cells with different TP53 status.

Resveratrol is a polyphenolic compound whose antitumor activity has been demonstrated in several types of cancer. However, there are few studies on its molecular mechanisms of action in bladder cancer. Therefore, we aimed to evaluate resveratrol activity in bladder tumour cells with different TP53 gene status. Cytotoxicity, cell proliferation, reactive oxygen species (ROS) production, cell migration, mutagenicity, and CDH1, CTNNBIP1, HAT1, HDAC1, MYC, and SMAD4 gene expression were evaluated. An increase in ROS after resveratrol treatment was accompanied by reduced cell viability and proliferation in all cell lines. In TP53 wild-type cells, the inhibition of cell migration was accompanied by CDH1 and SMAD4 modulation. In TP53 mutated cells, cell migration inhibition with CDH1 and CTNNB1P1 upregulation was observed. In conclusion, resveratrol has antiproliferative effect in bladder tumour cells and its mechanism of action occurred through ROS production, interference with cell cycle, and inhibition of cell migration, independent of TP53 status.

Modulation of non-coding RNAs by natural compounds as a potential therapeutical approach in oral cancer: A comprehensive review.

Oral cancer is a disease with high incidence and mortality worldwide, and its treatment still needs to be improved. The search for new therapies using natural products is strongly supported, given the wide chemical range of these compounds. In addition, phytochemicals can exert antitumor activities by several mechanisms of action, including the modulation of non-coding RNAs. Thus, in this review, we discussed the role of non-coding RNAs, including circular RNAs, microRNAs, and long non-coding RNAs, in oral cancer and presented their potential as treatment targets using natural products. Some natural products capable of being used to treat oral cancer have been suggested.

Sodium butyrate-loaded nanoparticles coated with chitosan for the treatment of neovascularization in age-related macular degeneration: Ocular biocompatibility and antiangiogenic activity.

Sodium butyrate-loaded nanoparticles coated chitosan (NaBu-loaded nanoparticles/CS) were developed to treat the choroidal neovascularization in wet age-related macular degeneration (AMD). The nanoparticles were produced by double emulsification and solvent evaporation technique, optimized by experimental statistical design, characterized by analytical methods, investigated in terms of in vitro and in vivo ocular biocompatibility, and evaluated as an antiangiogenic system in vivo. The NaBu-loaded nanoparticles/CS were 311.1 ± 3.1 nm in diameter with a 0.208 ± 0.007 polydispersity index; had a +56.3 ± 2.6 mV zeta potential; showed a 92.3 % NaBu encapsulation efficiency; and sustained the drug release over 35 days. The NaBu-loaded nanoparticles/CS showed no toxicity to human retinal pigment epithelium cells (ARPE-19 cells); was not irritant to the chorioallantoic membrane (CAM); did not interfere in the integrity of the retinal layers of rat's eyes, as detected by the Optical Coherence Tomography and histopathology; and inhibited the angiogenesis in CAM assay. The NaBu-loaded nanoparticles/CS could be a therapeutic alternative to limit the neovascularization in AMD.

Cytotoxic activity of butanolic extract from Sambucus nigra L. flowers in natura and vehiculated in micelles in bladder cancer cells and fibroblasts.

Bladder cancer has a high incidence and recurrence rate among patients worldwide. This study aimed to evaluate the cytotoxic activity of fractions of Sambucus nigra L. flower extracts on bladder carcinoma cells (T24 cells) and human fibroblast cells (MRC-5). The butanolic fraction (F-BuOH) was characterized by UPLC-DAD-MS/MS and nine flavonoids were identified. Rutin was the major compound. The cytotoxic activity of this fraction was observed in the T24 cells but not in MRC-5 cells, indicating selectivity. F-BuOH was incorporated in micellar solutions of Pluronic® F127 and cytotoxic effect for T24 cells was observed again. In vitro assay demonstrated a controlled release of the fraction from the micelles. The results obtained showed that flavonoids are the possible responsible for cytotoxic activity in bladder carcinoma cells. In addition, micellar solutions act together to increase the action of the butanolic fraction.

Modulation of Long Non-coding RNAs by Different Classes of Secondary Metabolites from Plants: A Mini-review on Antitumor Effects.

The broad pharmacological spectrum of plants is related to their secondary metabolism, which is responsible for the synthesis of different compounds that have multiple effects on cellular physiology. Among the biological effects presented by phytochemicals, their use for the prevention and treatment of cancer can be highlighted. This occurs due to several mechanisms of antitumor action demonstrated by these compounds, including regulation of the cell signaling pathways and inhibition of tumor growth. In this way, long non-coding RNAs (lncRNAs) appear to be promising targets for the treatment of cancer. Their deregulation has already been related to a variety of clinicalpathological parameters. However, the effects of secondary metabolites on lncRNAs are still restricted. For this reason, the present review aimed to gather data on phytochemicals with action on lncRNAs in order to confirm their possible antitumor potential. According to the literature, terpenoid and flavonoid are the main examples of secondary metabolites involved with lncRNAs activity. In addition, the lncRNAs H19, CASC2, HOTAIR, NKILA, CCAT1, MALAT1, AFAP1-AS1, MEG3, and CDKN2B-AS1 can be highlighted as important targets in the search for new anti-tumor agents since they act as modulating pathways related to cell proliferation, cell cycle, apoptosis, cell migration and invasion. Finally, challenges for the use of natural products as a commercial drug were also discussed. The low yield, selectivity index and undesirable pharmacokinetic parameters were emphasized as a difficulty for obtaining these compounds on a large scale and for improving the potency of its biological effect. However, the synthesis and/or development of formulations were suggested as a possible approach to solve these problems. All of these data together confirm the potential of secondary metabolites as a source of new anti-tumor agents acting on lncRNAs.

Additive effects of resveratrol and doxorubicin on bladder cancer cells.

The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2 µM) in combination with RES (150, 200 and 250 µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.

Resveratrol effects in oral cancer cells: a comprehensive review.

Oral cancer is a very common tumor worldwide with high incidence and mortality. The treatment of oral cancer involves surgery, radio- and chemotherapy; however, high failure rates and toxicity are noticed. Thus, the search of new drugs aiming a more effective treatment is welcomed. Natural products present chemopreventive and anti-cancer effects. Resveratrol is a naturally occurring antioxidant that contains several health benefits, including anti-inflammatory and antiproliferative activities. This review discusses the different action mechanisms of resveratrol related in the in vitro and in vivo studies using models of oral cancer.

Resveratrol effects in bladder cancer: A mini review.

Bladder cancer has a high incidence worldwide and is the most common genitourinary cancer. The treatment of bladder cancer involves surgery and chemotherapy; however high failure rates and toxicity are observed. In this context, the search of new drugs aiming a more effective treatment is extremely necessary. Natural products are an important source of compounds with antiproliferative effects. Resveratrol is a naturally occurring plant polyphenol whose anticancer activity has been demonstrated in different types of cancer. This review summarizes the in vitro and in vivo studies using models of bladder cancer treated with resveratrol and discusses its different mechanisms of action.

In silico pharmacological prediction and cytotoxicity of flavonoids glycosides identified by UPLC-DAD-ESI-MS/MS in extracts of Humulus lupulus leaves cultivated in Brazil.

Ethanolic (EB) extract and hexanic (SH) and hydromethanolic (SEM) sub-extracts of Humulus lupulus leaves were submitted to cytotoxicity evaluation and to phytochemical methods. The effect of EB and SEM on cellular cycle was evaluated by propidium iodide method and the phases were quantified through flow cytometry. The cytotoxicity assessment was done using T24 and MRC5 cells, with EB and SEM (25-1200 µg/mL). By means of UPLC-DAD-MS/MS data were identified the flavonoids astragaline, nicotiflorin, kaempferol-7-O-rutinoside, robinin, hyperin, rutin, quercetin-7-O-rutinoside and manghaslin. EB (800 µg/mL) and SEM (1200 µg/mL) reduces the T24 cell viability. These extracts at 25 µg/mL stimulate the growth of MRC5 cells, evidencing a selective cytotoxicity. After 24 h of the treatment with extracts was not observed cycle arrest of T24 cells. The bioactivity prediction of the flavonoids was evaluated in silico through in house Active-IT software and PASSonline which indicated potential activity as antitumoral, cytotoxic, anti-inflammatory, antiparasitic, antimicrobial, antiviral and others.

Antitumor effect of Cymbopogon densiflorus (Linneu) essential oil in bladder cancer cells.

The aim of this study was to analyse the antitumor effect of the Cymbopogon densiflorus essential oil in silico and in vitro on bladder cancer cells RT4 and T24, with different TP53 status. The oil was extracted by hydrodistillation and the gas chromatography coupled to the mass spectrometry was used for characterisation. In silico analysis was carried out by Pass online software. Cytotoxicity, cell proliferation, cell cycle progression, apoptosis and wound healing assays were performed. Five major compounds were identified. In silico analysis showed that major compounds present high potential for antitumor activities. The treatment with C. densiflorus essential oil reduced cell viability of bladder cancer cells. Only in wild-type cells, the increase of apoptosis rates and the decrease of cell migration were observed. In conclusion, the C. densiflorus essential oil presents antitumor effects on TP53 wild-type and mutated bladder cancer cells, however, the mechanism of action is TP53 status-dependent.[Figure: see text].

Toxicogenetic and antiproliferative effects of chrysin in urinary bladder cancer cells.

The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status.

Antibacterial substances from leaves of Protium spruceanum (Burseraceae): in vitro and in silico evaluation

Due to the increase of bacterial resistance, the search for new antibiotics is necessary and the medicinal plants represent its most important source. The aim of this study was to evaluate the antibacterial property of extract and fractions from Protium spruceanum leaves, against pathogenic bacteria. By means of diffusion and microdilution assays, the crude extract was active against the nine bacteria tested being the hydromethanolic fraction the most active. During phytochemical procedures, procyanidin (1) and catechin (2) were identified as the main antibacterial constituents of this fraction. In silico results obtained using PASSonline tool indicated 1 and 2 as having good potential to interact with different targets of currently used antibiotics. These results no indicated potential to none DNA effect and indicated the cell wall as mainly target. Electrophoresis result supported that had no DNA damage. Cell wall damage was confirmed by propidium iodide test that showed increased membrane permeability and by cell surface deformations observed in scanning electronic microscopy. The in vitro assays together with the in silico prediction results establish the potential of P. spruceanum as source of antibacterial compounds that acts on important bacterial targets. These results contribute to the development of natural substances against pathogenic bacteria and to discovery of new antibiotics.

Polymeric micelles containing resveratrol: development, characterization, cytotoxicity on tumor cells and antimicrobial activity

Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.

Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status.

The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 µM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740-751, 2019. © 2019 Wiley Periodicals, Inc.

Behavior of two Leishmania infantum strains-evaluation of susceptibility to antimonials and expression of microRNAs in experimentally infected J774 macrophages and in BALB/c mice.

Strains of the same Leishmania parasite species, isolated from different host organisms, may exhibit unique infection profiles and induce a change in the expression of microRNAs among host macrophages and in model host mice. MicroRNAs (MiR) are endogenous molecules of about 22 nucleotides that are involved in many regulatory processes, including the vertebrate host immune response. In this respect, the infectivity and susceptibility to antimonials of two L. infantum strains, BH46, isolated from human, and OP46, isolated from symptomatic dog, were characterized in J774 macrophages and BALB/c mice. Parasite burden was assessed in the liver, spleen, and bone marrow using the serial limiting dilution technique. A higher parasite burden was observed in the spleen and bone marrow of animals infected with OP46 compared to BH46 strain. Our results also showed that OP46 was less susceptible to the antimonials. In addition, miR-122 and miR-155 expression was evaluated in the liver and J774 macrophages, and in spleens from infected animals, respectively. An increase was observed in the expression of miR-155 in J774 macrophages infected with both strains compared to uninfected cells, with a higher expression in cells infected with OP46. However, no difference in the expression of miR-122 and miR-155 was observed in the infected animals. Thus, this study shows that OP46 was more infective for mice, it caused a higher increase in miR-155 expression in infected macrophages and was less susceptible to the antimonials evaluated. These data suggest that alteration in miR-155 level likely plays a role in regulating the response to L. infantum.