publications

2026

1. ESTIV early career network: A growing initiative to support the next generation of NAMs-oriented toxicologists

   Mohamed F. Abdallah, Luiz Ladeira, Peter Pôbiš, Andreas O. Stucki, Bambou Xuezhu Tan, Benoit Maisonneuve, Clive Roper, and Helena Kanďárová

   Toxicology in Vitro, Feb 2026
2. Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery

   Eliska Kuchovska, Kristina Bartmann, Georgea Raad, Mats Schade, Luiz Ladeira, Arif Dönmez, Jördis Klose, Nicolai Görts, Denis Polozij, Lynn‐Christin Saborowski, Farina Bendt, Bernard Staumont, and 3 more authors

   Advanced Science, Apr 2026

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   The Developmental Neurotoxicity (DNT) in vitro battery (IVB) enables efficient and human-relevant evaluation of chemicals for DNT potential. To expand its biological applicability domain toward human disease, this study maps neurodevelopmental disorder (NDD)-relevant signaling pathways to key neurodevelopmental processes (KNDPs) using primary human fetal neural progenitor cells (NPCs). Using pharmacological intervention, eighteen NDD pathways are assessed for their impact on seven KNDPs, namely NPC proliferation, radial glia migration, neuronal and oligodendrocyte differentiation and migration, and neurite outgrowth. In total, modulation of sixteen pathways is associated with changes in at least one KNDP. Oligodendrocyte differentiation shows the highest sensitivity (13 pathways), followed by radial glia migration (11 pathways) and NPC proliferation (9 pathways), whereas neuronal migration remains unaffected. Perturbation of the RhoA and mitochondrial complex I pathways is associated with the broadest phenotypic responses, influencing five KNDPs each, while STAT3- and TrkB-related modulation falls outside the assay’s applicability domain. Pathway-KNDP associations are integrated into an exemplary interactive physiological map of human oligodendrocyte development, linking mechanistic perturbations to human-relevant biology. Defining which NDD pathways can be functionally probed refines the DNT IVB’s biological applicability domain, increases confidence in its protective power, and supports mechanistic interpretation of new approach methodology-based DNT assessment.

3. Cardiotoxicity adverse outcome pathway network: towards mechanistic and quantitative modelling

   Luiz Ladeira, Devon A. Barnes, Rosalinde Masereeuw, Liesbet Geris, and Bernard Staumont

   Frontiers in Toxicology, May 2026

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   Introduction Chemical-induced heart toxicity remains a major challenge in drug development and environmental safety, largely because current testing often relies on narrow, late-stage endpoints that miss the complex biological progression of the toxicities. To address this, we developed a comprehensive Adverse Outcome Pathway (AOP) network that maps how early (bio) chemical triggers evolve into organ-level dysfunction. Methods By integrating data from the OECD AOP-Wiki, we constructed a unified network of 64 biological events and 94 documented relationships that identifies the critical biological “crossroads” where different toxic chemicals converge to cause heart damage. Results/discussion Our analysis reveals a compact core of central biological events, such as oxidative stress and mitochondrial dysfunction, which act as the primary drivers of cardiac injury. This network approach moves beyond single, linear pathways to show how systemic factors, including interactions with other organs like the kidneys, contribute to cardiotoxicity. To translate these findings into a practical resource for the broader scientific community, we developed a methods catalogue that links these biological events to specific laboratory assays. To ensure this work is accessible and actionable, we hosted the network on an interactive, FAIRaligned web platform. By providing a clear scaffold for understanding heart safety, this resource enables the design of more human-relevant, animal-free testing strategies and helps prioritise the most impactful biomarkers for future safety assessments.

2025

1. Exploring the safety parameters of Athenaea velutina ethanolic extract: a step towards harnessing its medicinal potential

   Jordana Luizi Dos Prazeres, Alisson Andrade Almeida, Renner Philipe Rodrigues Carvalho, Luiz Carlos Maia Ladeira, Luiz Pedro De Souza Costa, Markus Kohlhoff, Leandro Licursi De Oliveira, Mariana Machado-Neves, and João Paulo Viana Leite

   Toxicological Research, Jan 2025
2. Mapping Physiology: A Systems Biology Approach for the Development of Alternative Methods in Toxicology

   Bernard Staumont, Luiz Ladeira, Alessio Gamba, Harm J Heusinkveld, Aldert Piersma, Rosalinde Masereeuw, Tamara Vanhaecke, Marc Teunis, Thomas H Luechtefeld, Thomas Hartung, Ramiro Jover, Mathieu Vinken, and 1 more author

   ALTEX, Apr 2025

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   Chemical safety assessment still heavily relies on animal testing, presenting ethical dilemmas and limited human predictive value. New approach methodologies (NAMs), including in vitro and in silico techniques, offer alternative solutions. In silico toxicology has made progress in predicting chemical effects but frequently lacks biological mechanistic foundations. Recent developments focus on mechanistic understanding of adverse effects inflicted by chemicals, as embedded in (quantitative) adverse outcome pathways (AOPs). However, there is a demand for more detailed mechanistic insights at the gene and cell levels, encompassing both pathology and physiology. Drawing inspiration from the Disease Maps Project, this paper introduces Physiological Maps (PMs) as comprehensive graphical representations of biochemical processes related to specific organ functions. PMs are standardized using Systems Biology Graphical Notation and controlled vocabularies and annotations. Curation guidelines have been developed to ensure reproducibility and usability. This paper presents the methodology used to build PMs, emphasizing the essential collaboration between domain experts and curators. PMs offer userfriendly, standardized visualization for data analysis and educational purposes. Enabling a better understanding of (patho)physiology, they also complement and support the development of AOPs by providing detailed mechanistic information at the gene and cell level. Furthermore, PMs contribute to developing in vitro test batteries and to building (dynamic) in silico models aiming to predict the toxicity of chemicals. Collaborative efforts between the toxicology and systems biology communities are crucial for creating standardized and comprehensive PMs, supporting and accelerating the development of human-relevant NAMs for next-generation risk assessment.

3. Anti-adiposity effect of cipó-cravo (\textitTynanthus fasciculatus), a vine from the Brazilian Atlantic Forest

   Luiz Carlos Maia Ladeira, Eduardo Medeiros Damasceno, Aline Leão De Andrade Bandeira De Melo, Janaina Da Silva, Izabel Regina Dos Santos Costa Maldonado, and Sérgio Luis Pinto Da Matta

   Revista Brasileira de Plantas Medicinais, Jul 2025

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   Tynanthus fasciculatus (Vell.) Miers (Bignoniaceae) is a plant used in traditional medicine in southeastern Brazil, with aphrodisiac, antiparasitic, and tonic effects. Its extracts have a range of categories of active compounds identified, but their effects are scarcely reported in the scientific literature. We described, for the first time, the effects of T. fasciculatus infusion on body weight and adipose tissue depot weight in a Swiss mouse model. All studied doses (100, 200, and 300 mg/kg) caused a significant reduction in the weight of the interscapular brown adipose tissue and the epididymal white adipose tissue depots. The doses of 100 and 200 mg were also effective in controlling body weight gain. The infusion of T. fasciculatus was efficient in reducing adiposity and controlling weight gain.

4. Machine learning classification of steatogenic compounds using toxicogenomics profiles

   Brian Bwanya, Saad Lodhi, Theo M. De Kok, Luiz Ladeira, Marcha Ct Verheijen, Danyel Gj Jennen, and Florian Caiment

   Toxicology, Jul 2025
5. Unlocking liver physiology: comprehensive pathway maps for mechanistic understanding

   Luiz Ladeira, Anouk Verhoeven, Jonas Van Ertvelde, Jian Jiang, Alessio Gamba, Julen Sanz-Serrano, Tamara Vanhaecke, Harm J. Heusinkveld, Ramiro Jover, Mathieu Vinken, Liesbet Geris, and Bernard Staumont

   Frontiers in Toxicology, Jul 2025

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   Aims In silico methods provide a resourceful toolbox for new approach methodologies (NAMs). They can revolutionize chemical safety assessment by offering more efficient and human-relevant alternatives to traditional animal testing. In this study, we introduce two Liver Physiological Maps (PMs); comprehensive and machine-readable graphical representations of the intricate mechanisms governing two major liver functions. Methods Two PMs were developed through manual literature curation, integrating data from established pathway resources and domain expert knowledge. Cell-type specificity was validated using Human Protein Atlas datasets. An interactive version is available online for exploration. Cross-comparison analysis with existing Adverse Outcome Pathway (AOP) networks was performed to benchmark physiological coverage and identify knowledge gaps. Results The LiverLipidPM focuses on liver lipid metabolism, detailing pathways involved in fatty acid synthesis, triglycerides, cholesterol metabolism, and lipid catabolism in hepatocytes. And the LiverBilePM represents bile acid biosynthesis and secretion processes, detailing biosynthesis, transport, and secretion processes between hepatocytes and cholangiocytes. Both maps integrate metabolism with signaling pathways and regulatory networks. The interactive maps enable visualization of molecular pathways, linkage to external ontologies, and overlay of experimental data. Comparative analysis revealed unique mechanisms to each map and overlaps with existing AOP networks. Chemical-target queries identified new potential targets in both PMs, which might represent new molecular initiating events for AOP network extension. Conclusion The developed liver PMs serve as valuable resources for hepatology research, with a special focus on hepatotoxicity, supporting the refinement of AOP networks and the development of human-oriented in vitro test batteries for chemical toxicity assessment. These maps provide a foundation for creating computational models and mode-of-action ontologies while potentially extending their utility to systems biology and drug discovery applications.

6. From big data to smart decisions: artificial intelligence in kidney risk assessment

   Devon A. Barnes, Luiz Ladeira, and Rosalinde Masereeuw

   Nature Reviews Nephrology, Jul 2025
7. Building Immune Digital Twins: An International and Transdisciplinary Community Effort

   Anna Niarakis, Gary An, Luiz Ladeira, Noriko F. Hiroi, Athina Papadopoulou, Francis P. Crawley, Niloofar Nikaein, Laurence Calzone, Eirini Tsirvouli, Hasan Balci, Marina Esteban Medina, Lorenzo Veschini, and 19 more authors

   ImmunoInformatics, Sep 2025
8. From cellular perturbation to probabilistic risk assessments

   Alexandra Maertens, Breanne Kincaid, Eric Bridgeford, Celine Brochot, Arthur de Carvalho e Silva, Jean-Lou C. M. Dorne, Liesbet Geris, Trine Husøy, Nicole Kleinstreuer, Luiz C. M. Ladeira, Alistair Middleton, Joe Reynolds, and 5 more authors

   ALTEX, Jul 2025
9. Molecular exploration of host-pathogen interactions in severe Pseudomonas aeruginosa infection through a multi-level data integration approach

   Francesco Messina, Claudia Rotondo, Luiz Ladeira, Sara Crosetti, Michele Properzi, Valentina Dimartino, Benedetta Riccitelli, Bernard Staumont, Giovanni Chillemi, Liesbet Geris, Maria Grazia Bocci, and Carla Fontana

   Frontiers in Medicine, Oct 2025

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   IntroductionUnderstanding host-pathogen interactions is crucial for explaining the variability in sepsis outcomes, with Pseudomonas aeruginosa (PA) remaining a significant public health concern. In this work, we explored PA-human host interaction mechanisms through a data integration workflow, focusing on protein-protein and metabolite-protein interactions, along with pathway modulation in affected organs during severe infections.MethodsA scoping literature review enabled us to construct a domain-based infection network encompassing pathogenesis concepts, molecular interactions, and host response signatures, providing a wide view of the relevant mechanisms involved in severe bacterial infections.ResultsOur analysis yielded a literature-based comprehensive description of PA infection mechanisms and an annotated dataset of 189 PA-human interactions involving 151 proteins/molecules (109 human proteins, 3 human metabolites, 34 PA proteins, and 5 PA molecules). This dataset was complemented with gene expression analysis from in vivo PA-infected lung samples. The results indicated a notable overexpression of proinflammatory pathways and PA-mediated modulation of host lung responses.DiscussionOur comprehensive molecular network of PA infection represents a valuable tool for the understanding of severe bacterial infections and offers potential applications in predicting clinical phenotypes. Through this approach combining omics data, clinical information, and pathogen characteristics, we have provided a foundation for future research in host-pathogen interactions and the mechanistic grounds to build dynamic computational models for clinical phenotype predictions.

2024

1. Immune digital twins for complex human pathologies: applications, limitations, and challenges

   Anna Niarakis, Reinhard Laubenbacher, Gary An, Yaron Ilan, Jasmin Fisher, Åsmund Flobak, Kristin Reiche, María Rodríguez Martínez, Liesbet Geris, Luiz Ladeira, Lorenzo Veschini, Michael L. Blinov, and 35 more authors

   npj Systems Biology and Applications, Nov 2024

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   Abstract Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins. The immune response is complex and varies across diseases and patients, and its modelling requires the collective expertise of the clinical, immunology, and computational modelling communities. This review outlines the initial progress on immune digital twins and the various initiatives to facilitate communication between interdisciplinary communities. We also outline the crucial aspects of an immune digital twin design and the prerequisites for its implementation in the clinic. We propose some initial use cases that could serve as “ proof of concept ” regarding the utility of immune digital technology, focusing on diseases with a very different immune response across spatial and temporal scales (minutes, days, months, years). Lastly, we discuss the use of digital twins in drug discovery and point out emerging challenges that the scientific community needs to collectively overcome to make immune digital twins a reality.

2023

1. Toxicology of arsenate, arsenite, cadmium, lead, chromium, and nickel in testes of adult Swiss mice after chronic exposure by intraperitoneal route

   Francielle De Fátima Viana Santana, Janaina Da Silva, Amanda Alves Lozi, Diane Costa Araujo, Luiz Carlos Maia Ladeira, Leandro Licursi De Oliveira, and Sérgio Luis Pinto Da Matta

   Journal of Trace Elements in Medicine and Biology, Jul 2023

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   Background: Some residues such as the heavy metals cadmium (Cd), lead (Pb), chromium (Cr VI), nickel (Ni), and arsenic (As), this last one in its oxidized forms + 5 (arsenate) and + 3 (arsenite), can cause injuries to human health, so they are currently considered environmental health emergencies. In the testis, heavy metals can cause morphological and functional damage due to constant exposure acting chronically in individuals. Thus, we aimed to determine the toxicological mechanism of As+5, As+3, Cd, Cr VI, and Ni that leads to testicular damage and establish for the first time an order of toxicity among these studied heavy metals. Methods: Forty-two Swiss mice at reproductive age (140 days) were used, randomly distributed into seven experimental groups (n = 6). Exposure to heavy metals was weekly performed, by intraperitoneal route. Group 1 received 0.7 mL 0.9% saline (control), and the other groups received 1.5 mg/ kg of As+5, As+3, Cd, Pb, Cr VI, or Ni, for six weeks. Results: These studied heavy metals did not accumulate in the testis tissue. However, exposure to Ni induced moderate pathologies in the seminiferous tubules, plus changes in the tunica propria, blood vessels, lymphatic space, and carbonyl protein levels. Cd exposure caused moderate tubular histopathologies and changes in the blood vessels and lymphatic space. Cr VI induced slight tubular histopathologies, changes in the lymphatic space, blood vessels, and SOD activity. Pb and As+3 exposure triggered moderate tubular pathologies and changes in the SOD activity and carbonyl protein levels, respectively. Finally, As+5 induced only slight tubular pathologies. Conclusion: The testicular histopathologies caused by the studied heavy metals are mainly triggered by changes in testicular oxidative balance. Based on our findings of histomorphological alterations, the toxicity order among the heavy metals is Ni\textgreaterCd\textgreaterCr(VI)\textgreaterPb––As+3 \textgreaterAs+5. However, considering oxidative stress results, we propose the following testicular toxicity order for these heavy metals: Ni\textgreaterAs+3 \textgreater Cd\textgreaterCr(VI)\textgreaterPb\textgreaterAs+5. Ni exposure shows the most harmful among the heavy metals to the testis.

2. Exposure to Pfaffia glomerata causes oxidative stress and triggers hepatic changes

   F. C. R. Dias, M. C. Cupertino, P. G. Silva, E. L. Oliveira, L. C. M. Ladeira, S. L. P. Matta, W. C. Otoni, and M. L. M. Gomes

   Brazilian Journal of Biology, Jun 2023

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   Abstract Medicinal plant species are genetically engineered to obtain higher production of biomass and specific secondary metabolites, which can be used in the pharmaceutical industry. The aim of the present study was to evaluate the effect of Pfaffia glomerata (Spreng.) Pedersen tetraploid hydroalcoholic extract on the liver of adult Swiss mice. The extract was prepared from the plant roots and given to the animals by gavage, for 42 days. The experimental groups were treated with water (control), Pfaffia glomerata tetraploid hydroalcoholic extract (100, 200 and 400 mg/kg) and Pfaffia glomerata tetraploid hydroalcoholic extract discontinuously (200 mg/kg). The last group received the extract every 3 days, for 42 days. The oxidative status, mineral dynamics, and cell viability were analysed. The liver weight and the number of viable hepatocytes were reduced, despite the increased cell’s number. Increased levels of malondialdehyde and nitric oxide, and changes in iron, copper, zinc, potassium, manganese and sodium levels were observed. aspartate aminotransferase levels were increased while alanine aminotransferase levels were decreased due to BGEt intake. Our results showed that BGEt induced alterations of oxidative stress biomarkers leading to liver injury, which was associated with a reduction in the number of hepatocytes. , Resumo Espécies de plantas medicinais são geneticamente modificadas para obter maior produção de biomassa e metabólitos secundários específicos, que podem ser utilizados na indústria farmacêutica. O objetivo do presente estudo foi avaliar o efeito do extrato hidroalcoólico tetraploide de Pfaffia glomerata no fígado de camundongos suíços adultos. O extrato foi preparado a partir das raízes das plantas e administrado aos animais por gavagem, por 42 dias. Os grupos experimentais foram tratados com água (controle), extrato hidroalcoólico de Pfaffia glomerata tetraploide (100, 200 e 400 mg/kg) e extrato hidroalcoólico de Pfaffia glomerata tetraploide de forma descontinua (200 mg/kg). O último grupo recebeu o extrato a cada 3 dias, durante 42 dias. O estado oxidativo, a dinâmica mineral e a viabilidade celular foram analisados. O peso do fígado e o número de hepatócitos foram reduzidos, apesar do aumento do número de células. Observou-se aumento dos níveis de malondialdeído e óxido nítrico e alterações nos níveis de Ferro, Cobre, Zinco, potássio, Magnésio e sódio. Os níveis de aspartato aminotransferase aumentaram, enquanto os níveis de alanina aminotransferase diminuíram devido à ingestão do extrato. Nossos resultados mostraram que BGEt induziu alterações de biomarcadores de estresse oxidativo levando a lesão hepática, que foi associada a uma redução no número de hepatócitos.

2022

1. Chia (Salvia hispanica L.) Flour and Oil Ameliorate Metabolic Disorders in the Liver of Rats Fed a High-Fat and High Fructose Diet

   Luiza De Paula Dias Moreira, Bárbara Nery Enes, Vinícius Parzanini Brilhante De São José, Renata Celi Lopes Toledo, Luiz Carlos Maia Ladeira, Rodrigo Rezende Cardoso, Vinícius Da Silva Duarte, Helen Hermana Miranda Hermsdorff, Frederico Augusto Ribeiro De Barros, and Hércia Stampini Duarte Martino

   Foods, Jan 2022

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   We hypothesized that the consumption of chia (Salvia hispanica L.) flour (CF) and chia oil (CO) improves metabolic disorders in the liver of Wistar rats (Rattus norvegicus domestica) fed a high-fat and high-fructose (HFHF) diet. The animals were fed a HFHF diet (n = 30) or AIN93-M standard diet (n = 10) for eight weeks. After this period, the animals fed HFHF were divided into three groups (n = 10): HFHF diet, HFHF plus 14.7% of CF, and HFHF plus 4% of CO. Histological and biochemical analyses, gene expression, protein levels related to inflammation, and oxidative stress were evaluated in the liver. The HFHF diet caused lipogenesis, liver steatosis, oxidative stress, and inflammation in the animals. The CF and CO intake increased the liver total antioxidant capacity and superoxide dismutase, decreased nitric oxide levels and liver steatosis. Furthermore, the CF and CO led to the upregulation of Cpt1a and Adipor2, respectively, whereas CF downregulated Srebf1. CO intake decreased blood glucose, triglycerides, and the animals’ body weight. Chia did not show effects on mitigating liver pro-inflammatory status, which it may indicate occurs later. The addition of chia into an unbalanced diet is a good and relevant strategy to reduce liver metabolic disorders caused by the high consumption of fructose and saturated fat.

2021

1. Playfulness in the Teaching of Cell Biology: possibilities in higher education

   Nadja Biondine Marriel, Luiz Carlos Maia Ladeira, Renan Dos Santos Araújo, Janaina Da Silva, Ana Luiza Pereira Martins, and Mara Garcia Tavares

   Revista ELO – Diálogos em Extensão, Jun 2021

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   Considering the difficulties that some new students at the University present to understand abstract concepts, this work describes an extension course, in the area of Cell Biology, which was carried out with the objective of contributing to the effective learning of a group of undergraduate students at the University Federal University of Viçosa (MG). The work also reports the importance of the experience lived for the graduate students who taught the Course. In the Course, diversified recreational activities were used, chosen according to the theme that would be approached. The results showed that the process was very well accepted by the students, helping them to understand the contents, through a pleasant and accessible process, which enabled the construction of knowledge. For graduate students, the experience was unique and contributed to their professional training. Therefore, the results were significant for everyone involved

2. High-fat diet and caffeine interact to modulate bone microstructure and biomechanics in mice

   Fernanda Batista De Souza, Rômulo Dias Novaes, Cynthia Fernandes Ferreira Santos, Franciele Angelo De Deus, Felipe Couto Santos, Luiz Carlos Maia Ladeira, Reggiani Vilela Gonçalves, Daniel Silva Sena Bastos, Ana Cláudia Ferreira Souza, Mariana Machado-Neves, and Eliziária Cardoso Dos Santos

   Life Sciences, Jul 2021

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   Aims: Although excessive fat and caffeine intake are independent risk factors for bone microstructural and functional disturbances, their association remains overlooked. Thus, we investigated the impact of high-fat diet (HFD) and caffeine alone and combined on serum lipid profile, bone microstructure, micromineral distribution and biomechanical properties. Methods: Forty female C57BL/6 mice were randomized into 4 groups daily treated for seventeen weeks with standard diet (SD) or HFD (cafeteria diet) alone or combined with 50 mg/kg caffeine. Key findings: The association between HFD and caffeine reduced the weight gain compared to animals receiving HFD alone. Caffeine alone or combined with HFD increases total and HDL cholesterolcirculating levels. HFD also reduced calcium, phosphorus and magnesium bone levels compared to the groups receiving SD, and this reduction was aggravated by caffeine coadministration. From biomechanical assays, HFD combined with caffeine increased bending strength and stiffness of tibia, a finding aligned with the marked microstructural remodeling of the cortical and cancellous bone in animals receiving this combination. Significance: Our findings indicated that HFD and caffeine interact to induce metabolic changes and bone microstructural remodeling, which are potentially related to bone biomechanical adaptations in response to HFD and caffeine coadministration.

3. Green tea infusion prevents diabetic nephropathy aggravation in recent-onset type 1 diabetes regardless of glycemic control

   Luiz Carlos Maia Ladeira, Eliziária Cardoso Dos Santos, Talita Amorim Santos, Janaina Da Silva, Graziela Domingues De Almeida Lima, Mariana Machado-Neves, Renê Chagas Da Silva, Mariella Bontempo Freitas, and Izabel Regina Dos Santos Costa Maldonado

   Journal of Ethnopharmacology, Jun 2021

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   Ethnopharmacological relevance: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies. Aim: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes. Material and methods: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney. Results: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment. Conclusion: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia.

4. Green Tea Infusion Ameliorates Histological Damages in Testis and Epididymis of Diabetic Rats

   Luiz Otávio Guimarães-Ervilha, Luiz Carlos Maia Ladeira, Renner Philipe Rodrigues Carvalho, Isabela Pereira Da Silva Bento, Daniel Silva Sena Bastos, Ana Cláudia Ferreira Souza, Eliziária Cardoso Santos, Leandro Licursi De Oliveira, Izabel Regina Dos Santos Costa Maldonado, and Mariana Machado-Neves

   Microscopy and Microanalysis, Jan 2021

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   Abstract Green tea is a popular drink used for therapeutic purposes to mitigate the consequences of diabetes. In this study, we aimed at evaluating the potential of green tea infusion to ameliorate structural and enzymatic damages caused by hyperglycemia in the testis and epididymis of Wistar rats. For that, nondiabetic and streptozotocin-induced diabetic rats (negative control and diabetes control, respectively) received 0.6 mL of water by gavage. Another set of diabetic animals received 100 mg/kg of green tea infusion diluted in 0.6 mL of water/gavage (diabetes + green tea) daily. After 42 days of treatment, the testes and epididymides were removed and processed for histopathological analysis, micromineral determination, and enzymatic assays. The results showed that treatment with green tea infusion preserved the testicular and epididymal histoarchitecture, improving the seminiferous epithelium and the sperm production previously affected by diabetes. Treatment with green tea reduced tissue damages caused by this metabolic condition. Given the severity of hyperglycemia, there was no efficacy of the green tea infusion in maintaining the testosterone levels, antioxidant enzyme activity, and microminerals content. Thus, our findings indicate a protective effect of this infusion on histological parameters, with possible use as a complementary therapy for diabetes.

5. Different Routes of Administration Lead to Different Oxidative Damage and Tissue Disorganization Levels on the Subacute Cadmium Toxicity in the Liver

   Viviane Gorete Silveira Mouro, Luiz Carlos Maia Ladeira, Amanda Alves Lozi, Thiago Soares De Medeiros, Mariany Ribeiro Silva, Elizabeth Lopes De Oliveira, Fabiana Cristina Silveira Alves De Melo, and Sérgio Luis Pinto Da Matta

   Biological Trace Element Research, Jan 2021

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   The toxic effects of cadmium (Cd) on hepatic parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.) because it is easier to apply, while in the oral route, Cd poisoning in humans is best represented by allowing the metal to pass through the digestive system and be absorbed into the bloodstream. Thus, this study investigated the Cd exposure impact on the liver, by comparing both i.p. and oral routes, both in single dose, in addition to the oral route in fractional doses. Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral single dose, and 4.28 mg/kg oral route in fractional doses for 7 consecutive days. Cd bioaccumulation was observed in all animals exposed to Cd. Hepatic concentrations of Ca and Fe increased only in the fractionated oral route. Liver activities of SOD and CAT increased only by oral single dose. GST decreased in all forms of oral administration, while MDA decreased only in i.p. route. Liver weight and HSI increased in the i.p. route, while organ volume increased in all forms of oral administration, and liver density increased in all animals exposed to Cd. In hepatic histomorphometry, the changes were more evident in oral administration, mainly in exposure to metal in a single dose. Thus, the subacute administration of Cd in different routes of administration leads to different changes in liver poisoning.

6. Chronic caffeine use does not influence behavior and brain oxidative status in mice: O uso crônico de cafeína não influencia o comportamento e o status oxidativo em camundongos

   Túlio Pereira Alvarenga E Castro, Luiz Carlos Maia Ladeira, Cynthia Fernandes Ferreira Santos, Franciele Ângelo De Deus, Arthur Rocha Gomes, Daniel Silva Sena Bastos, Ana Cláudia Ferreira Souza, and Eliziária Cardoso Dos Santos

   Revista da Associação Brasileira de Nutrição - RASBRAN, Jul 2021

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   Widely consumed in foods and as an energy supplement, caffeine has been studied given its pharmacological effects, especially on Central Nervous System (CNS). In this sense, the present study investigated whether and to what extent caffeine chronic use can influence the brain oxidative status and the behavioral activity of the C57BL/6 female mice. For this, fifteen animals were randomized into the following groups: Control (0.9% saline solution), Caf10 (10 mg/kg caffeine), and Caf50 (50 mg/kg caffeine). The animals received one daily caffeine dose by i.p route for 120 days. Twenty-four hours after the last administration, the animals were subjected to behavioral tests and euthanized. The blood was used by biochemical analysis and the brain to evaluate the oxidative status and micromineral levels. The caffeine did not influence the anthropometric parameters, lipid profile, and Creactive protein levels. Further, superoxide dismutase (SOD) and glutathione-stransferase (GST) activities maintained the same response profile. On the other hand, catalase (CAT) activity was decreased in both groups receiving caffeine compared to the control group. Despite this, malondialdehyde and carbonyl protein levels did not change among the groups, as well as the distribution micromineral levels. In the same way, no caffeine dose altered the findings of anxiety-like behaviors in the animals. Considering the time of caffeine administration, we believe that there was a cellular adaptation triggered by its use, tending to a protective effect on the brain.

7. Cardioprotective action of chia ( \textitSalvia hispanica L.) in ovariectomized rats fed a high fat diet

   Marcella Duarte Villas Mishima, Luiz Carlos Maia Ladeira, Bárbara Pereira Da Silva, Renata Celi Lopes Toledo, Thomás Valente De Oliveira, Neuza Maria Brunoro Costa, and Hércia Stampini Duarte Martino

   Food & Function, Feb 2021

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   The combination of ovariectomy with high fat diet consumption, in this study, affected biometric parameters, oxidative stress, mineral content and ATPase pump activity, while chia consumption had positive effects on these factors. , The reduction in estrogen levels is associated with the increased risk factors for cardiovascular disease development. The present study aimed to evaluate the effect of chia consumption in a standard diet (SD) or high fat diet (HFD) on ovariectomized (OVX) and non-ovariectomized (SHAM) rats, in relation to biometric measurements, oxidative stress, mineral content and ATPase enzymes in the heart. The study was conducted with 80 female Wistar rats, which received a SD or HFD for 18 weeks. During the first 7 weeks, the animals received the SD or HFD. Then, 40 rats were ovariectomized and 40 rats were SHAM operated. After recovery from surgery, the animals were allocated to 8 groups ( n = 10) and they received one of the following diets for 8 weeks: SD, SD + chia, HFD and HFD + chia. In the OVX group, HFD increased weight gain, adiposity, cardiac hypertrophy, and nitric oxide (NO) and K concentration and decreased the Na + /K + ATPase activity. In combination with HFD, ovariectomy decreased the catalase activity, Mg, Cu and Zn concentration, total ATPase activity, and Na + /K + ATPase and Mg2 + ATPase activities; this group also presented higher NO, Ca, K, Fe and Mn concentration in the heart. The SHAM group fed chia presented a lower fat content in the heart. In the OVX group fed HFD, chia increased the activity of superoxide dismutase, decreased NO and maintained the content of minerals and ATPase enzymes. Thus, chia improved the biometric parameters of the heart, the antioxidant activity and maintained the content of minerals and ATPase enzymes, showing a cardioprotective action, but without reversing the deleterious effects of ovariectomy.

2019

1. Could biological tissue preservation methods change chemical elements proportion measured by energy dispersive X-ray spectroscopy?

   Luiz Carlos Maia Ladeira, Eliziária Cardoso Dos Santos, Gilmar Edilberto Valente, Janaina Da Silva, Talita Amorim Santos, and Izabel Regina Dos Santos Costa Maldonado

   Biological Trace Element Research, Oct 2019

   Abs

   Energy dispersive X-ray spectroscopy (EDS) is a powerful technical tool used in the biomedical field to investigate the proportion of chemical elements of interest in research, such as heavy metal bioaccumulation and the enzymatic cofactors and nanoparticle therapy in various pathologies. However, the correct evaluation of the proportion of the elements is subject to some factors, including the method of sample preservation. In this study, we seek to investigate the effect of biological tissue preservation methods on the proportion of chemical elements obtained by the EDS methodology. For such, we used EDS to measure the proportion of chemical elements with biomedical interest in preserved livers, using three common methods for preserving biological tissues: (a) freezing, (b) paraformaldehyde fixative solution, and (c) Karnovsky solution. We found an increased level of sodium and reduced contents of potassium and copper in samples fixed in fixative solutions, when compared to frozen samples (p \textless 0.05). Our data indicate that preservation methods can change the proportion of chemical elements in biological samples, when measured by EDS. Frozen preservation should be preferred to retain the actual chemical content of samples and allow a correct assessment of the proportion of their elements.