ANGELICA BUENO BARBEZAN

ANGELICA BUENO BARBEZAN

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Evaluations of the possible mutagenic and genotoxic effects of 2-ACBs
2024 - BARBEZAN, A.B.; BISPO, A.C.A.; MENDES, B.M.; VIEIRA, D.P.; CARVALHO, L.R.; MACHADO-SANTELLI, G.M.; VILLAVICENCIO, A.L.C.H.
Radioactive gold nanoparticles coated with BSA
2024 - BARBEZAN, ANGELICA B.; ROSERO, WILMMER A.A.; VIEIRA, DANIEL P.; RIGO, MARIA E.Z.; SILVA, GIOVANA D. da; RODRIGUES, ALEX A.; ALMEIDA, LUIS F. de; SILVA, FABIO F.A. da; RIVERA, ANDY G.; SILVA, NATANAEL G. da; BERNARDES, EMERSON S.; ZEITUNI, CARLOS A.; ROSTELATO, MARIA E.C.M.
Background: Nanotechnology has revolutionized medicine, especially in oncological treatments. Gold nanoparticles (AuNPs) stand out as an innovative alternative due to their biocompatibility, potential for surface modification, and effectiveness in radiotherapeutic techniques. Given that prostate cancer ranks as one of the leading malignancies among men, there's a pressing need to investigate new therapeutic approaches. Methods: AuNPs coated with bovine serum albumin (BSA) were synthesized and their cytotoxicity was assessed against prostate tumor cell lines (LNCaP and PC-3), healthy prostate cells (RWPE-1), and endothelial control cells (HUVEC) using the MTS/PMS assay. For in vivo studies, BALB/C Nude mice were employed to gauge the therapeutic efficacy, biodistribution, and hematological implications post-treatment with BSA-coated AuNPs. Results: The BSA-coated AuNPs exhibited cytotoxic potential against PC-3 and LNCaP lines, while interactions with RWPE-1 and HUVEC remain subjects for further scrutiny. Within animal models, a diverse therapeutic response was observed, with certain instances indicating complete tumor regression. Biodistribution data emphasized the nanoparticles' affinity towards particular organs, and the majority of hematological indicators aligned with normative standards. Conclusions: BSA-coated AuNPs manifest substantial promise as therapeutic tools in treating prostate cancer. The present research not only accentuates the nanoparticles' efficacy but also stresses the imperative of optimization to ascertain both selectivity and safety. Such findings illuminate a promising trajectory for avant-garde therapeutic modalities, holding substantial implications for public health advancements.
Evaluation of cytotoxicity through MTS test of 2-ACBs (2-dDCB AND tDCB) after exposure to hepatic cells
2019 - BARBEZAN, A.B.; CARVALHO, L.R.; VIEIRA, D.P.; MACHADO-SANTELLI, G.M.; MARTINS, R.; VILLAVICENCIO, A.L.C.H.
Food irradiation has been approved in more than 60 countries for many applications in a wide variety of foods. 2-Alkylcyclobutanones (2-ACBs) are the only known radiolytic products formed when foods containing fatty acids are irradiated. Despite the importance of food irradiation, the toxicological potential of 2-ACBs in irradiated food is still no fully understood. In this study we investigated the cytotoxic effects of irradiated palmitic and stearic fatty acids byproducts, 2-dDCB and 2-tDCB, in hepatic cell lines (HepG2, BRL3A and HTC). The cytotoxic effects of 2-dDCB and 2-tDCB were evaluated at 100, 300 and 500 μM for 24 and 48 hours and the cell viability was measured using the MTS assay. While no toxicity was observed for 2-tDCB in all cells for all tested conditions, 2-dDCB was found to be toxic to BRL3A cells (at 100 μM after 48 hours) and HTC cells (at 24 hours in all tested concentrations). HepG2 cells on the other hand, were found to be resistant to 2-dDCB-induced toxicity. Overall our data shows that the byproduct 2-tDCB is not toxic for hepatic cells while 2-dDCB can be used has a potential marker for food irradiation-induced toxicity.
Synthesis, in vitro testing, and biodistribution of surfactant-free radioactive nanoparticles for cancer treatment
2022 - SOUZA, CARLA D. de; BARBEZAN, ANGELICA B.; ROSERO, WILMMER A.A.; SANTOS, SOFIA N. dos; CARVALHO, DIEGO V. de S.; ZEITUNI, CARLOS A.; BERNARDES, EMERSON S.; VIEIRA, DANIEL P.; SPENCER, PATRICK J.; RIBEIRO, MARTHA S.; ROSTELATO, MARIA E.C.M.
New forms of cancer treatment, which are effective, have simple manufacturing processes, and easily transportable, are of the utmost necessity. In this work, a methodology for the synthesis of radioactive Gold-198 nanoparticles without the use of surfactants was described. The nuclear activated Gold-198 foils were transformed into H198AuCl4 by dissolution using aqua regia, following a set of steps in a specially designed leak-tight setup. Gold-198 nanoparticles were synthesized using a citrate reduction stabilized with PEG. In addition, TEM results for the non-radioactive product presented an average size of 11.0 nm. The DLS and results for the radioactive 198AuNPs presented an average size of 8.7 nm. Moreover, the DLS results for the PEG-198AuNPs presented a 32.6 nm average size. Cell line tests showed no cytotoxic effect in any period and the concentrations were evaluated. Furthermore, in vivo testing showed a high biological uptake in the tumor and a cancer growth arrest.
In vivo genotoxicity of 2-alkylcyclobutanones in liver cells from rats fed with irradiated cocoa butter using flow cytometry
2021 - MARTINS, R.; VIEIRA, D.P.; CARVALHO, L.R.; BARBEZAN, A.B.; VILLAVICENCIO, A.L.C.H.
Food irradiation proves to be an effective technique of eliminating some pathogens from food and this has gained significant attention to its potential for food safety. Since 1990, studies on the toxicological safety of 2-Alkylcyclobutanones have been conducted extensively. 2-Alkylcyclobutanones are unique radiolytic products generated by the radiation-induced breakage of triglycerides in food, 2-dodecylcyclobutanone (2-dDCB) and 2-tetradecylcyclobutanone (2-tDCB) are the predominant compounds detected . Despite studies showing non-genotoxicity of 2-ACBs (2-Alkylcyclobutanones), the results are conflicting and therefore we continue the studies in order to confirm the compounds are safety for human health. In vivo micronucleus test were performed to verify the 2-ACBs genotoxic effects in hepatic cells using flow cytometry. We used cocoa butter irradiated with 20 kGy. A group with animals was treated with daily intake of irradiated cocoa butter, synthesized 2-dDCB and 2-tDCB for one month. Hepatic cells were selected for genotoxicity analysis due to the liver importance in the compounds metabolization. The improvement of the analytical techniques is important for the research future since the irradiation process is already consolidated. The results confirmed the safety of the food irradiation process, as they did not indicate the genotoxic potential of the samples.
In vivo genotoxicity of 2-Alkylcyclobutanones in liver cells from rats fed with irradiated cocoa butter using flow citometry
2019 - MARTINS, REGIANE; VIEIRA, DANIEL P.; CARVALHO, LUMA R. de; BARBEZAN, ANGELICA B.; VILLAVICENCIO, ANNA L.C.H.
Food irradiation proves to be an effective technique of eliminating some pathogens from food and this has gained significant attention to its potential for food safety. Since 1990, studies on the toxicological safety of 2-Alkylcyclobutanones have been conducted extensively. 2- Alkylcyclobutanones are unique radiolytic products generated by the radiation-induced breakage of triglycerides in food, are exclusively found in irradiated lipid containing foods. 2-dodecylcyclobutanone (2-dDCB) and 2-tetradecylcyclobutanone (2-tDCB) are the predominant compounds detected in irradiated food. Despite studies showing non- genotoxicity of 2-ACBs (2-Alkylcyclobutanones), the results are conflicting and therefore we continue the studies in order to confirm the compounds safety for human health. In vivo micronucleus test were performed to verify the 2-ACBs genotoxic effects in hepatic cells using flow citometry. We used cocoa butter irradiated with 20 kGy at IPEN GAMACELL. A group with animals (IPEN Ethical Animal Experimentation Committee, process number 148/14) was treated with daily intake of irradiated cocoa butter, synthesized 2- Dodecylcyclobutanone and 2-Tetradecylcyclobutanone for two months. Hepatic cells were selected for genotoxicity analysis due to the liver importance in the compounds metabolization. Analyzes were made by micronucleus test with specific cells extracted from hepatic tissue using flow cytometry, which is an alternative to conventional techniques, allowing faster analysis and reduction in the animals number that is a subject much approached in research today. The improvement of the analytical techniques is important for the research future since the irradiation process is already consolidated. The results confirmed the safety of the food irradiation process, as they did not indicate the genotoxic potential of the samples.
Flow cytometry based micronucleus assay for evaluation of genotoxic potential of 2-ACBs in hepatic cells HepG2
2019 - BARBEZAN, ANGELICA B.; SANTOS, CARLA J.B.; CARVALHO, LUMA R.; VIEIRA, DANIEL P.; SANTELLI, GLAUCIA M.M.; VILLAVICENCIO, ANNA L.C.H.
Food irradiation is approved for use in more than 60 countries for applications and purposes in a wide variety of foods, being an effective and safe method for preservation and long-term storage. 2- Alkylcyclobutanones (2-ACBs) are the only known radiolytic products generated from foods that contain fatty acids (Triglycerides) when irradiated. The acids analyzed in this study are palmitic and stearic, which when irradiated form 2-Dodecylcyclobutanones (2-dDCB) and 2-Tetradecylcyclobutanone (2-tDCB). Part of the 2-ACBs ingested is excreted through feces and part is deposited in adipose tissues. In vitro studies so far have been only in colon cells. The work used a human hepatoma cell line (HepG2) since the accumulation of fat in this organ is quite common. Micronucleus test was selected to evaluate possible genotoxic effects of 2-dDCB and 2-tDCB compounds when exposed to high concentrations (447, 1422 and 2235 μM) for 4 and 24 hours. Tests were performed in quadriplicates using flow cytometric analysis. None detectable genotoxic damage was observed after 4 hours of exposure to the compounds, and cytotoxic effects were only significant at the highest concentration (2235 μM) of 2-dDCB. After 24 hours of exposure, slight genotoxic damage was observed at all concentrations evaluated, and cytotoxic effects were only present when exposed to compound 2-tDCB. Although there is a genotoxic and cytotoxic effect in some of the situations tested, the two compounds predominantly induced proliferation reduction effects of this hepatic tumor cell line.
In vivo evaluation of genotoxic potential of liver cells from rats fed with irradiated diet using flow cytometry
2017 - MARTINS, R.; CARVALHO, L.R. de; VIEIRA, D.P.; BARBEZAN, A.B.; VILLAVICENCIO, A.L.C.H.
Radiation sources became widely available since 1960’s, and between its main uses are the applications in food irradiation and research of effects of ionizing radiation on food products. Despite some public concern, the process is safe, free from chemical residues and presents advantages for preservation and storage. Nevertheless, safety dose parameters must be adopted in irradiation procedures to inhibit formation of undesirable and/or toxic products, for example, 2-ACB’s (2-alkylcyclobutanones) that are cyclic compounds containing four carbon rings that can be formed in food when its fat content is irradiated through breakdown of fatty acids. 2-ACBs are considered a unique class of compounds due to divergences between results of its mutagenicity potential collected from different studies. In this study, a cell population collected from rat livers were chosen for in vivo genotoxicity analysis because the importance of the liver in the metabolization of compounds. Analysis was performed using the micronuclei test using flow cytometry, allowing faster analysis, use of few materials and reduction in the number of animals, what is a subject much addressed currently in research. Irradiated rat diet did not show any genotoxic effect on liver cell populations. The improvement of the techniques is important for the future of the research since the irradiation process is already consolidated.
Flow cytometry based micronucleus assay for evaluation of genotoxic potential of 2-ACBs in hepatic cells HepG2
2017 - BARBEZAN, ANGELICA B.; SANTOS, CARLA J.B.; CARVALHO, LUMA R.; VIEIRA, DANIEL P.; SANTELLI, GLAUCIA M.M.; VILLAVICENCIO, ANNA L.C.H.
Food irradiation is approved for use in more than 60 countries for applications and purposes in a wide variety of foods, being an effective and safe method for preservation and long-term storage. 2-Alkylcyclobutanones (2-ACBs) are the only known radiolytic products generated from foods that contain fatty acids (Triglycerides) when irradiated. The acids analyzed in this study are palmitic and stearic, which when irradiated form 2-Dodecylcyclobutanones (2-dDCB) and 2-Tetradecylcyclobutanone (2-tDCB). Part of the 2-ACBs ingested is excreted through feces and part is deposited in adipose tissues. In vitro studies so far have been only in colon cells. The work used a human hepatoma cell line (HepG2) since the accumulation of fat in this organ is quite common. Micronucleus test was selected to evaluate possible genotoxic effects of 2-dDCB and 2-tDCB compounds when exposed to high concentrations (447, 1422 and 2235 μM) for 4 and 24 hours. Tests were performed in quadriplicates using flow cytometric analysis. None detectable genotoxic damage was observed after 4 hours of exposure to the compounds, and cytotoxic effects were only significant at the highest concentration (2235 μM) of 2-dDCB. After 24 hours of exposure, slight genotoxic damage was observed at all concentrations evaluated, and cytotoxic effects were only present when exposed to compound 2-tDCB. Although there is a genotoxic and cytotoxic effect in some of the situations tested, the two compounds predominantly induced proliferation reduction effects of this hepatic tumor cell line.