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7. Effect of Oral Zinc Supplementation on Phase Angle and Bioelectrical Impedance Vector Analysis in Duchenne Muscular Dystrophy: A Non-Randomized Clinical Trial.

Author

Vermeulen-Serpa, Karina Marques, Lopes, Márcia Marilia Gomes Dantas, Alves, Camila Xavier, Grilo, Evellyn Camara, Cunha, Thais Alves, Miranda, Carolinne Thaisa de Oliveira Fernandes, Bezerra, Breno Gustavo Porfirio, Leite-Lais, Lucia, Brandão-Neto, José, and Vale, Sancha Helena de Lima

Abstract

Zinc plays a crucial role in cell structure and functionality. Neurodegenerative Duchenne muscular dystrophy (DMD) alters muscle membrane structure, leading to a loss of muscle mass and strength. The objective of this study was to evaluate the changes in phase angle (PA) and bioelectrical impedance vector analysis (BIVA) results in patients with DMD after oral zinc supplementation. This clinical trial included 33 boys aged 5.6 to 24.5 years diagnosed with DMD. They were divided into three groups according to age (G1, G2, and G3) and supplemented with oral zinc. The mean serum zinc concentration was 74 μg/dL, and 29% of patients had concentrations below the reference value. The baseline values (mean (standard deviation)) of the bioelectrical impedance parameters PA, resistance (R), and reactance (Xc) were 2.59° (0.84°), 924.36 (212.31) Ω, and 39.64 (8.41) Ω, respectively. An increase in R and a decrease in PA and lean mass proportional to age were observed, along with a negative correlation (r = −0.614; p < 0.001) between age and PA. The average cell mass in G1 was greater than that in G3 (p = 0.012). There were no significant differences in serum zinc levels or bioelectrical impedance parameters before and after zinc supplementation. We conclude that this population is at risk of zinc deficiency and the proposed dosage of zinc supplementation was not sufficient to alter serum zinc levels, PA and BIVA results. [ABSTRACT FROM AUTHOR]

Published
2024
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9. An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.

Author

Keedy, Daniel A, Hill, Zachary B, Biel, Justin T, Kang, Emily, Rettenmaier, T Justin, Brandão-Neto, José, Pearce, Nicholas M, von Delft, Frank, Wells, James A, and Fraser, James S

Abstract

Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here, we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function.

Published
2018

10. Effect of Zinc Supplementation on Body Composition of Duchenne Muscular Dystrophy Patients: A Quasi‐Experimental Study.

Author

Cunha, Thais A., Vermeulen-Serpa, Karina M., Grilo, Evellyn C., Dourado-Júnior, Mário E. T., Bezerra, Breno G. P., Torres, Núbia R. S. M., Lopes, Márcia M. G. D., Leite-Lais, Lucia, Brandão-Neto, José, Vale, Sancha H. L., and Gumpricht, Eric

Abstract

Background. The study hypothesized that zinc supplementation would increase or preserve lean body mass in Duchenne muscular dystrophy (DMD) patients. Therefore, we aimed to evaluate the body composition of DMD patients before and after zinc supplementation. Materials and Methods. The study is a clinical trial comprising 21 boys diagnosed with DMD. Dietary intake parameters were evaluated before zinc supplementation. Serum zinc levels, anthropometry, and body composition were measured in three moments, four months apart. The patients received 5, 10, or 15 mg of zinc bis‐glycine supplementation according to age as an oral solution daily for four months. The sample was distributed into two groups according to serum zinc status: zinc deficiency (G1) or adequate zinc (G2). Results. There was a significant difference in lean body mass between the groups: zinc deficiency (G1) or adequate zinc (G2), at three times (p = 0.041, 0.016, and 0.009, respectively). After oral zinc supplementation, serum zinc levels were not different between groups. We did not observe differences when associating the parameters between times and groups. Conclusion. Zinc supplementation was able to maintain lean body mass and fat mass in patients with DMD with previous deficiencies. Therefore, it is necessary to have a prior screening of serum zinc levels to observe changes after supplementation. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Zinc and thyroid cancer: A systematic review and meta-analysis protocol.

Author

Soares, Aline Alves, Nagashima, Yasmin Guerreiro, Alves, Camila Xavier, de Medeiros, Kleyton Santos, Lopes, Márcia Marília Gomes Dantas, and Brandão-Neto, José

Subjects
THYROID cancer, THYROID gland, CANCER patients, CARCINOGENESIS, TRACE elements
Abstract

Introduction: The thyroid cancer has the ninth larger incidence of cancer in the world. Investigations related to the exposure to metals have become important due to the sensibility of the thyroid gland to them. Studies reveal that carcinogenic progressions are associated to the deficiency of the essential trace elements. In this context, the zinc is highlighted, essential for the metabolism of the thyroidal hormone and has a potential relation with the pathogenesis of the thyroid cancer. The objective of this systematic review and meta-analysis is to evaluate the low serum zinc as a risk factor for thyroid cancer in adults. Methods and analysis: PubMed/MEDLINE, Scopus, Embase and LILACS databases will be searched for observational studies investigating the low serum zinc as a risk factor for thyroid cancer in adults. No language or publication period restrictions will be imposed. The primary outcome will be that the low serum zinc is a risk factor for thyroid cancer. Three independent reviewers will select the studies and extract data from the original publications. The risk-of-bias will be assessed by using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data synthesis will be performed using the R software (V.4.3.1) and to assess heterogeneity, we will compute the I2 statistic and the results will be based on either random-effects or fixed-effects models, depending on the heterogeneity. The Grading of Recommendations, Development, and Evaluation (GRADE) system will be used to evaluate the reliability and quality of evidence. Prospero registration number: International Prospective Register of Systematic Reviews (PROSPERO) CRD42023463747. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Fragment library screening by X-ray crystallography and hit optimization against thioredoxin glutathione reductase of Schistosoma mansoni

Author

Neto, Lauro Ribeiro Souza, primary, Montoya, Bogar Omar, additional, Moreira-Filho, José Teófilo, additional, Brandão-Neto, José, additional, Verma, Anil, additional, Bowyer, Sebastian, additional, Dantas, Rafael Ferreira, additional, Neves, Bruno Junior, additional, Delft, Frank, additional, Owens, Raymond J., additional, Furnham, Nicholas, additional, Andrade, Carolina Horta, additional, and Silva, Floriano Paes, additional

Published
2023
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17. Zinc supplementation reduces RANKL/OPG ratio and prevents bone architecture alterations in ovariectomized and type 1 diabetic rats

Author

Ferreira, Elaine C.S., Bortolin, Raul H., Freire-Neto, Francisco P., Souza, Karla S.C., Bezerra, João F., Ururahy, Marcela A.G., Ramos, Ana M.O., Himelfarb, Silvia T., Abreu, Bento J., Didone, Thiago V.N., Pedrosa, Lucia F.C., Medeiros, Aldo C., Doi, Sonia Q., Brandão-Neto, José, Hirata, Rosário D.C., Rezende, Luciana A., Almeida, Maria G., Hirata, Mario H., and Rezende, Adriana A.

Published
2017
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18. Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease

Author

Douangamath, Alice, Fearon, Daren, Gehrtz, Paul, Krojer, Tobias, Lukacik, Petra, Owen, C. David, Resnick, Efrat, Strain-Damerell, Claire, Aimon, Anthony, Ábrányi-Balogh, Péter, Brandão-Neto, José, Carbery, Anna, Davison, Gemma, Dias, Alexandre, Downes, Thomas D., Dunnett, Louise, Fairhead, Michael, Firth, James D., Jones, S. Paul, Keeley, Aaron, Keserü, György M., Klein, Hanna F., Martin, Mathew P., Noble, Martin E. M., O’Brien, Peter, Powell, Ailsa, Reddi, Rambabu N., Skyner, Rachael, Snee, Matthew, Waring, Michael J., Wild, Conor, London, Nir, von Delft, Frank, and Walsh, Martin A.

Published
2020
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20. Crystal structure of an antifungal osmotin-like protein from Calotropis procera and its effects on Fusarium solani spores, as revealed by atomic force microscopy: Insights into the mechanism of action

Author

Ramos, Marcio V., de Oliveira, Raquel S.B., Pereira, Humberto M., Moreno, Frederico B.M.B., Lobo, Marina D.P., Rebelo, Luciana M., Brandão-Neto, José, de Sousa, Jeanlex S., Monteiro-Moreira, Ana C.O., Freitas, Cléverson D.T., and Grangeiro, Thalles Barbosa

Published
2015
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24. Microbiota Intestinal e Esclerose Lateral Amiotrófica

Author

Vilar, Mariana Dantas de Carvalho, Vale, Sancha Helena de Lima, Rosado, Eliane Lopes, Dourado Júnior, Mário Emílio Teixeira, Brandão-Neto, José, Leite-Lais, Lúcia, Vilar, Mariana Dantas de Carvalho, Vale, Sancha Helena de Lima, Rosado, Eliane Lopes, Dourado Júnior, Mário Emílio Teixeira, Brandão-Neto, José, and Leite-Lais, Lúcia

Abstract

O trato gastrintestinal humano é povoado por uma grande quantidade de microrganismos. Essa microbiota intestinal (MI) tem uma relação de mutualismo com o organismo humano e desempenha papel fundamental na regulação de funções metabólicas, endócrinas e imunológicas. A disbiose intestinal está associada a fenótipos de várias doenças crônicas e inflamatórias. Essa associação é explicada pelas funções da MI e a existente comunicação bidirecional do eixo microbiota-intestino-cérebro.  Nos últimos anos, estudos têm mostrado novas evidências entre a MI e as doenças neurodegenerativas, incluindo a esclerose lateral amiotrófica (ELA). Diante disso, essa revisão narrativa discorre de forma didática sobre a MI, suas funções, sua relação com o sistema neuro-imuno-endócrino e sua associação com as doenças neurodegenerativas, com ênfase na ELA., The human gastrointestinal tract contains numerous microorganisms. This intestinal microbiota (IM) has a mutualistic relationship with the human organism, and it plays a fundamental role in regulating metabolic, endocrine, and immunological functions. Intestinal dysbiosis is associated with phenotypes of many chronic and inflammatory diseases. This association is explained by the functions of the IM and the existing bi-directional communication of the microbiota-intestine-brain axis. Studies have uncovered new evidence between the IM and neurodegenerative diseases recently, including amyotrophic lateral sclerosis (ALS). Given this, the present narrative review discusses didactically about IM, its functions, its relationship with the neuroimmune-endocrine system, and its association with neurodegenerative diseases, with emphasis on ALS.

Published
2022

25. Intestinal Microbiota and Sclerosis Lateral Amyotrophic

Author

Vilar, Mariana Dantas de Carvalho, Vale, Sancha Helena de Lima, Rosado, Eliane Lopes, Dourado Júnior, Mário Emílio Teixeira, Brandão-Neto, José, Leite-Lais, Lúcia, Vilar, Mariana Dantas de Carvalho, Vale, Sancha Helena de Lima, Rosado, Eliane Lopes, Dourado Júnior, Mário Emílio Teixeira, Brandão-Neto, José, and Leite-Lais, Lúcia

Abstract

The human gastrointestinal tract contains numerous microorganisms. This intestinal microbiota (IM) has a mutualistic relationship with the human organism, and it plays a fundamental role in regulating metabolic, endocrine, and immunological functions. Intestinal dysbiosis is associated with phenotypes of many chronic and inflammatory diseases. This association is explained by the functions of the IM and the existing bi-directional communication of the microbiota-intestine-brain axis. Studies have uncovered new evidence between the IM and neurodegenerative diseases recently, including amyotrophic lateral sclerosis (ALS). Given this, the present narrative review discusses didactically about IM, its functions, its relationship with the neuroimmune-endocrine system, and its association with neurodegenerative diseases, with emphasis on ALS., O trato gastrintestinal humano é povoado por uma grande quantidade de microrganismos. Essa microbiota intestinal (MI) tem uma relação de mutualismo com o organismo humano e desempenha papel fundamental na regulação de funções metabólicas, endócrinas e imunológicas. A disbiose intestinal está associada a fenótipos de várias doenças crônicas e inflamatórias. Essa associação é explicada pelas funções da MI e a existente comunicação bidirecional do eixo microbiota-intestino-cérebro.  Nos últimos anos, estudos têm mostrado novas evidências entre a MI e as doenças neurodegenerativas, incluindo a esclerose lateral amiotrófica (ELA). Diante disso, essa revisão narrativa discorre de forma didática sobre a MI, suas funções, sua relação com o sistema neuro-imuno-endócrino e sua associação com as doenças neurodegenerativas, com ênfase na ELA.

Published
2022

26. Kinetics of zinc status and zinc deficiency in Berardinelli-Seip syndrome

Author

Santos, Maria Goretti do Nascimento, Baracho, Maria de Fátima Paiva, Vale, Sancha Helena de Lima, Leite, Lúcia Dantas, Rocha, Érika Dantas de Medeiros, Brito, Naira Josele Neves de, França, Mardone Cavalcante, Almeida, Maria das Graças, Chiquetti, Samanta Cristina, Marchini, Júlio Sérgio, and Brandão-Neto, José

Published
2012
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29. Phenolic Composition, Toxicity Potential, and Antimicrobial Activity of Licania rigida Benth (Chrysobalanaceae) Leaf Extracts

Author

Morais, Leandro Vinícius Fernandes de, primary, Luz, Jefferson Romáryo Duarte da, additional, Nascimento, Thayse Evellyn Silva do, additional, Azevedo, Marcelo Arrison dos Santos, additional, Rocha, Walicyranison Plínio da Silva, additional, Araujo-Silva, Gabriel, additional, Ururahy, Marcela Abbott Galvão, additional, Chaves, Guilherme Maranhão, additional, Brandão-Neto, José, additional, López, Jorge A., additional, dos Santos, Elizabeth Cristina Gomes, additional, and Almeida, Maria das Graças, additional

Published
2022
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30. Identification of NID1 as a novel candidate susceptibility gene for familial non-medullary thyroid carcinoma using whole-exome sequencing

Author

de Mello, Luis Eduardo Barbalho, primary, Carneiro, Thaise Nayane Ribeiro, additional, Araujo, Aline Neves, additional, Alves, Camila Xavier, additional, Galante, Pedro Alexandre Favoretto, additional, Buzatto, Vanessa Candiotti, additional, das Graças de Almeida, Maria, additional, Vermeulen-Serpa, Karina Marques, additional, de Lima Vale, Sancha Helena, additional, José de Pinto Paiva, Fernando, additional, Brandão-Neto, José, additional, and Cerutti, Janete Maria, additional

Published
2022
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33. Licania rigida leaf extract: Protective effect on oxidative stress, associated with cytotoxic, mutagenic and preclinical aspects

Author

Batista, Débora, primary, Romáryo Duarte da Luz, Jefferson, additional, Evellyn Silva Do Nascimento, Thayse, additional, Felipe de Senes-Lopes, Tiago, additional, Araújo Galdino, Ony, additional, Victor E Silva, Saulo, additional, Pinheiro Ferreira, Macelia, additional, Arrison dos Santos Azevedo, Marcelo, additional, Brandão-Neto, José, additional, Araujo-Silva, Gabriel, additional, López, Jorge A., additional, and das Graças Almeida, Maria, additional

Published
2021
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35. Crystallographic approach to fragment-based hit discovery against Schistosoma mansoni purine nucleoside phosphorylase

Author

Faheem, Muhammad, primary, Fonseca Valadares, Napoleão, additional, Brandão-Neto, José, additional, Bellini, Dom, additional, Collins, Patrick, additional, Pearce, Nicholas M., additional, Bird, Louise, additional, Roberta Torini, Juliana, additional, Owens, Raymond, additional, DMuniz Pereira, Humberto, additional, Von Delft, Frank, additional, and Barbosa, João Alexandre Ribeiro Gonçalves, additional

Published
2021
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38. Structural and Evolutionary Analyses of PR-4 SUGARWINs Points to a Different Pattern of Protein Function

Author

Maia, Lorhenn Bryanda Lemes, primary, Pereira, Humberto D’Muniz, additional, Garratt, Richard Charles, additional, Brandão-Neto, José, additional, Henrique-Silva, Flavio, additional, Toyama, Danyelle, additional, Dias, Renata O., additional, Bachega, José Fernando Ruggiero, additional, Peixoto, Julia Vasconcellos, additional, and Silva-Filho, Marcio C., additional

Published
2021
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39. Orientational Ambiguity in Septin Coiled Coils and its Structural Basis

Author

Fundação de Amparo à Pesquisa do Estado de São Paulo, Leonardo, Diego A., Cavini, Italo A., Sala, Fernanda A., Mendonça, Deborah C., Rosa, Higor V.D., Kumagai, Patricia S., Crusca Jr, Edson, Valadares, Napoleão F., Marques, Ivo A., Brandão-Neto, José, Munte, Claudia E., Kalbitzer, Hans R., Soler, Nicolas, Usón, Isabel, André, Ingemar, Araujo, Ana P.U., D'Muniz Pereira, Humberto, Garratt, Richard C., Fundação de Amparo à Pesquisa do Estado de São Paulo, Leonardo, Diego A., Cavini, Italo A., Sala, Fernanda A., Mendonça, Deborah C., Rosa, Higor V.D., Kumagai, Patricia S., Crusca Jr, Edson, Valadares, Napoleão F., Marques, Ivo A., Brandão-Neto, José, Munte, Claudia E., Kalbitzer, Hans R., Soler, Nicolas, Usón, Isabel, André, Ingemar, Araujo, Ana P.U., D'Muniz Pereira, Humberto, and Garratt, Richard C.

Abstract

Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These sequences therefore code for two metastable states of different orientations which employ different but overlapping interfaces. The antiparallel structures present a mixed coiled-coil interface, one side of which is dominated by a continuous chain of core hydrophilic residues. This unusual type of coiled coil could be used to expand the toolkit currently available to the protein engineer for the design of previously unforeseen coiled-coil based assemblies. Within a physiological context, our data provide the first atomic details related to the assumption that the parallel orientation is likely formed between septin monomers from the same filament whilst antiparallelism may participate in the widely described interfilament cross bridges necessary for higher order structures and thereby septin function.

Published
2021

42. Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats

Author

Jatobá, Carlos André Nunes, de Rezende, Adriana Augusto, de Paiva Rodrigues, Sarah Jane, de Almeida Câmara, Maria Margareth, das Graças Almeida, Maria, Freire-Neto, Francisco, da Rocha, Luiz Reginaldo Menezes, da Medeiros, Aldo Cunha, Brandão-Neto, José, de Carvalho Formiga, Maria Célia, de Azevedo, Ítalo Medeiros, and de Oliveira Ramos, Ana Maria

Published
2008
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43. Orientational Ambiguity in Septin Coiled Coils and its Structural Basis

Author

Leonardo, Diego A., primary, Cavini, Italo A., additional, Sala, Fernanda A., additional, Mendonça, Deborah C., additional, Rosa, Higor V.D., additional, Kumagai, Patricia S., additional, Crusca Jr, Edson, additional, Valadares, Napoleão F., additional, Marques, Ivo A., additional, Brandão-Neto, José, additional, Munte, Claudia E., additional, Kalbitzer, Hans R., additional, Soler, Nicolas, additional, Usón, Isabel, additional, André, Ingemar, additional, Araujo, Ana P.U., additional, D'Muniz Pereira, Humberto, additional, and Garratt, Richard C., additional

Published
2021
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45. Structure, Mechanism and Crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase

Author

Newman, Joseph A, primary, Douangamath, Alice, additional, Yazdani, Setayesh, additional, Yosaatmadja, Yuliana, additional, Aimon, Anthony, additional, Brandão-Neto, José, additional, Dunnett, Louise, additional, Gorrie-stone, Tyler, additional, Skyner, Rachel, additional, Fearon, Daren, additional, Schapira, Matthieu, additional, von Delft, Frank, additional, and Gileadi, Opher, additional

Published
2021
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47. Prolactin and zinc in dialysis patients

Author

Castro, Ana V. B., Caramori, Jacqueline, Barretti, Pasqual, Baptistelli, Elda E., Brandão, Ambrósio, Barim, Estela M., Padovani, Carlos R., Aragon, Flávio F., and Brandão-Neto, José

Published
2002
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49. Licania rigida leaf extract: Protective effect on oxidative stress, associated with cytotoxic, mutagenic and preclinical aspects.

Author

Batista, Débora, Romáryo Duarte da Luz, Jefferson, Evellyn Silva Do Nascimento, Thayse, Felipe de Senes-Lopes, Tiago, Araújo Galdino, Ony, Victor E Silva, Saulo, Pinheiro Ferreira, Macelia, Arrison dos Santos Azevedo, Marcelo, Brandão-Neto, José, Araujo-Silva, Gabriel, López, Jorge A., and das Graças Almeida, Maria

Subjects
CHO cell, GENETIC toxicology, OXIDATIVE stress, MUTAGENS, PLANT diversity, GLUTATHIONE peroxidase
Abstract

Brazilian plant biodiversity is a rich alternative source of bioactive compounds since plant-derived extracts and/or their secondary metabolites exhibit potential properties to treat several diseases. In this context, Licania rigida Benth (Chrysobalanaceae Family), a large evergreen tree distributed in Brazilian semi-arid regions, deserves attention for its widespread use in popular medicine, although its biological properties are still poorly studied. The aim of this study was to examine (1) acute and sub-chronic oral toxicity at 2000 mg/kg dose; (2) in vitro cytotoxicity at 0.1; 1; 10; 100 or 1000 µg/ml; (3) in vivo mutagenicity at 5, 10 or 20 mg/ml, and (4) potential antioxidant protective effect of L. rigida aqueous leaf extract of (AELr). No marked apparent toxic and genotoxic effects were observed using in vitro and in vivo assays after in vitro treatment of Chinese hamster ovary cell line (CHO-K1) with AELr or in vivo exposure of Wistar rats and Drosophila melanogaster to different extract concentrations. Concerning the antioxidant effect, the extract exhibited a protective effect by decreasing lipid peroxidation as determined by malondialdehyde levels. No significant changes were observed for glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Data demonstrate the beneficial potential of AELr to be employed for therapeutic purposes. However, further studies are required to validate the pharmacological application of this plant extract to develop as a phytotherapeutic formulation. [ABSTRACT FROM AUTHOR]

Published
2022
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50. Lack of acute zinc effect on thyrotropin-releasing hormone–stimulated thyroid-stimulating hormone secretion during oral zinc tolerance test in healthy men

Author

Brandão-Neto, José, Saturnino, Ana Conceição Ribeiro Dantas, Leite, Lúcia Dantas, de Medeiros Rocha, Érika Dantas, Marcos, Christiane Maria Passos, da Silva, Carlos Antônio Bruno, Marchini, Júlio Sérgio, de Rezende, Adriana Augusto, Almeida, Maria das Graças, and Medeiros, Aldo da Cunha

Published
2006
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