LUIZ FELIPE DOMINGUES PASSERO
Projetos de Pesquisa
Unidades Organizacionais
LIM/50 - Laboratório de Patologia das Moléstias Infecciosas, Hospital das Clínicas, Faculdade de Medicina
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article 24 Citação(ões) na Scopus Chemical Composition and in vitro Cytotoxic and Antileishmanial Activities of Extract and Essential Oil from Leaves of Piper cernuum(2015) CAPELLO, Tabata M.; MARTINS, Euder G. A.; FARIAS, Camyla F. de; FIGUEIREDO, Carlos R.; MATSUO, Alisson L.; PASSERO, Luiz Felipe D.; OLIVEIRA-SILVA, Diogo; SARTORELLI, Patricia; LAGO, Joao Henrique G.Fractionation of the MeOH extract from leaves of Piper cernuum Veil. (Piperaceae) afforded six phenylpropanoid derivatives: 3',4'-dimethoxydihydrocinnamic acid (1), piplaroxide (2), methyl 4'-hydroxy-3',5'-dimethoxy cinnamate (3), 3',4',5'-trimethoxydihydrocinnamic acid (3), dihydropiplartine (5), and piplartine (6). The structures of isolated metabolites were characterized by NMR and MS spectral data analysis. The chemical composition of essential oil from the leaves was determined using GC/LREIMS followed by the determination of Kovats indexes. This procedure allowed the identification of nineteen terpenoids, with beta-elemene (7), bicyclogermacrene (8), germacrene D (9), and (E)-caryophyllene (10) as the main compounds. Compounds 1 and 3-6 displayed no in vitro cytotoxicity against cancer cell lineages B16F10-Nex2, U87, HeLa, HL-60, HCT, and A2058 while 2 showed moderate activity against B16F10-Nex2 and HL-60 lines. Otherwise, compounds 7-10 displayed high cytotoxic activity. Evaluation against non-tumorigenic HFF cells indicated a reduced selectivity of compounds 7-10 to tumoral cells. No antileishmanial activity on macrophages infected with L. (L.) amazonensis was found for the crude MeOH extract and compounds 1-6. The crude essential oil and compounds 7-10 reduced parasitism and eliminated the majority of infected and non-infected cells at 50 mu g/mL.- Antimicrobial Activity of Oleanolic and Ursolic Acids: An Update(2015) JESUS, Jessica A.; LAGO, Joao Henrique G.; LAURENTI, Marcia D.; YAMAMOTO, Eduardo S.; PASSERO, Luiz Felipe D.Triterpenoids are the most representative group of phytochemicals, as they comprise more than 20,000 recognized molecules. These compounds are biosynthesized in plants via squalene cyclization, a C-30 hydrocarbon that is considered to be the precursor of all steroids. Due to their low hydrophilicity, triterpenes were considered to be inactive for a long period of time; however, evidence regarding their wide range of pharmacological activities is emerging, and elegant studies have highlighted these activities. Several triterpenic skeletons have been described, including some that have presented with pentacyclic features, such as oleanolic and ursolic acids. These compounds have displayed incontestable biological activity, such as antibacterial, antiviral, and antiprotozoal effects, which were not included in a single review until now. Thus, the present review investigates the potential use of these triterpenes against human pathogens, including their mechanisms of action, via in vivo studies, and the future perspectives about the use of compounds for human or even animal health are also discussed.
- The Effect of Ursolic Acid on Leishmania (Leishmania) amazonensis Is Related to Programed Cell Death and Presents Therapeutic Potential in Experimental Cutaneous Leishmaniasis(2015) YAMAMOTO, Eduardo S.; CAMPOS, Bruno L. S.; JESUS, Jessica A.; LAURENTI, Marcia D.; RIBEIRO, Susan P.; KALLAS, Esper G.; RAFAEL-FERNANDES, Mariana; SANTOS-GOMES, Gabriela; SILVA, Marcelo S.; SESSA, Deborah P.; LAGO, Joao H. G.; LEVY, Debora; PASSERO, Luiz F. D.Among neglected tropical diseases, leishmaniasis is one of the most important ones, affecting more than 12 million people worldwide. The available treatments are not well tolerated, and present diverse side effects, justifying the search for new therapeutic compounds. In the present study, the activity of ursolic acid (UA) and oleanolic acid (OA) were assayed in experimental cutaneous leishmaniasis (in vitro and in vivo). Promastigote forms of L. amazonensis were incubated with OA and UA for 24h, and effective concentration 50% (EC50) was estimated. Ultraestructural alterations in Leishmania amazonensis promastigotes after UA treatment were evaluated by transmission electron microscopy, and the possible mode of action was assayed through Annexin V and propidium iodide staining, caspase 3/7 activity, DNA fragmentation and transmembrane mitochondrial potential. The UA potential was evaluated in intracellular amastigotes, and its therapeutic potential was evaluated in L. amazonensis infected BALB/c mice. UA eliminated L. amazonensis promastigotes with an EC50 of 6.4 mu g/mL, comparable with miltefosine, while OA presented only a marginal effect on promastigote forms at 100 mu g/mL. The possible mechanism by which promastigotes were eliminated by UA was programmed cell death, independent of caspase 3/7, but it was highly dependent on mitochondria activity. UA was not toxic for peritoneal macrophages from BALB/c mice, and it was able to eliminate intracellular amastigotes, associated with nitric oxide (NO) production. OA did not eliminate amastigotes nor trigger NO. L. amazonensis infected BALB/c mice submitted to UA treatment presented lesser lesion size and parasitism compared to control. This study showed, for the first time, that UA eliminate promastigote forms through a mechanism associated with programed cell death, and importantly, was effective in vivo. Therefore, UA can be considered an interesting candidate for future tests as a prototype drug for the treatment of cutaneous leishmaniasis.
- Analysis of iron superoxide dismutase-encoding DNA vaccine on the evolution of the Leishmania amazonensis experimental infection(2015) CAMPOS, B. L. S.; SILVA, T. N.; RIBEIRO, S. P.; CARVALHO, K. I. L.; KALLAS, E. G.; LAURENTI, M. D.; PASSERO, L. F. D.The present work aimed to evaluate the immunogenicity of Leishmania amazonensis iron superoxide dismutase (SOD) -encoding DNA experimental vaccine and the protective properties of this DNA vaccine during infection. The SOD gene was subcloned into the pVAX1 plasmid, and it was used to immunize BALB/c mice. Twenty-one days after the last immunization, mice were sacrificed (immunogenicity studies) or subcutaneously challenged with L. amazonensis (studies of protection), and alterations in cellular and humoral immune responses were evaluated, as well as the course of infection. Mice only immunized with pVAX1-SOD presented increased frequencies of CD4(+) IFN-gamma(+), CD8(+) IFN- gamma(+) and CD8(+) IL-4(+) lymphocytes; moreover, high levels of IgG2a were detected. After challenge, mice that were immunized with pVAX1-SOD had increased frequencies of the CD4(+) IL- 4(+), CD8(+) IFN-gamma(+) and CD8(+) IL-4(+) T lymphocytes. In addition, the lymph node cells produced high amounts of IFN-gamma and IL-4 cytokines. Increased IgG2a was also detected. The pattern of immunity induced by pVAX1-SOD partially protected the BALB/c mice from a challenge with L. amazonensis, as the animals presented reduced parasitism and lesion size when compared to controls. Taken together, these results indicate that leishmanial SOD modulates the lymphocyte response, and that the elevation in IFN-gamma possibly accounted for the decreased skin parasitism observed in immunized animals.
- New insights into neutrophil and Leishmania infantum in vitro immune interactions(2015) MARQUES, Claudia S.; PASSERO, Luiz Felipe D.; VALE-GATO, Ines; RODRIGUES, Armanda; RODRIGUES, Olivia Roos; MARTINS, Catarina; CORREIA, Ivone; TOMAS, Ana M.; ALEXANDRE-PIRES, Graca; FERRONHA, M. Helena; SANTOS-GOMES, Gabriela M.The interaction between polymorphonuclear leukocytes (PMN) or neutrophils and Leishmania became an interesting focus of research, since PMN turn out to be essential cells in transiently hosting the parasites. This study aims to evaluate whether L. infantum, the etiological agent of zoonotic visceral leishmaniasis, influences the in vitro functional activity of murine neutrophils. Phagocytosis, chemotaxis, oxidative burst, degranulation and apoptosis assays were performed. Cytokines, chemokines and toll-like receptors gene expression were evaluated by Real-time PCR. Results indicate that some of the innate features of PMN immunity were activated when in contact with L. infantum. However, parasites might negatively interfere with PMN defense mechanisms compromising the link between innate and acquired immunity. This work provides additional insights on the inflammatory immune interactions between neutrophils and L. infantum highlighting the role of PMN in Leishmania infection.
- Differential modulation of macrophage response elicited by glycoinositolphospholipids and lipophosphoglycan from Leishmania (Viannia) shawi(2015) PASSERO, Luiz F. D.; ASSIS, Rafael R.; SILVA, Thays N. F. da; NOGUEIRA, Paula M.; MACEDO, Diego H.; PESSOA, Natalia L.; CAMPOS, Marco A.; LAURENTI, Marcia D.; SOARES, Rodrigo P.In this work, some aspects of the glycobiology of Leishmattia shawl were examined, as it is a causative agent of cutaneous leishmaniasis in the New World. Additionally, the interaction of L. shawl's main glycoconjugates [lipophosphoglycan (LPG) and glycoinositolphospholipids (GIPLs)] with macrophages was evaluated in vitro. L. shawl LPG was devoid of side-chains in its repeat units, whereas monosaccharide analysis showed that GIPLs were suggestive of mannose-rich (type I or hybrid). In order to evaluate the biological roles of those molecules, BALB/c resident peritoneal macrophages were incubated with these glycoconjugates for 24 h, and the levels of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-12p70 and IL-10, were determined. In general, the GIPLs exhibited a greater proinflammatory role than the LPGs did. However, for the first time, the GIPLs from this species were able to trigger the production of IL-10, an anti-inflammatory cytokine. In conclusion, L shawl glycoconjugates were able to interact with the innate immune compartment. These data reinforce the role of parasite glycoconjugates during parasite and host cell interactions.