Fábio Rodrigues Ferreira Seiva

@uenp.edu.br

Universidade Estadual do Norte do Paraná - UNEP/CLM



              

https://researchid.co/fabioseiva
19

Scopus Publications

Scopus Publications

  • Long-term effects of maternal protein restriction on adrenal proteomic profile and steroidogenesis in male offspring rats
    Matheus Naia Fioretto, Luísa Annibal Barata, Vinícius Alexandre de Andrade Felipe, Sérgio Alexandre Alcantara dos Santos, Flávia Alessandra Maciel, Isabelle Tenori Ribeiro, Renato Mattos, Hecttor Sebástian Baptista, Gabriela Bueno, Felipe Leonardo Fagundes,et al.
    Elsevier BV

  • Maternal protein restriction and postnatal sugar consumption increases inflammatory response and deregulates metabolic pathways in the liver of male offspring rats with aging
    Isabelle Tenori Ribeiro, Matheus Naia Fioretto, Sérgio Alexandre Alcantara dos Santos, Marcus Vinicius Niz Alvarez, Luiz Marcos Frediani Portela, Renato Mattos, Hecttor Baptista Sebastian, Pedro Menchini Vitali, Fábio Rodrigues Ferreira Seiva, Luís Fernando Barbisan,et al.
    Elsevier BV

  • In Silico Analysis of Non-Conventional Oxidative Stress-Related Enzymes and Their Potential Relationship with Carcinogenesis
    Fábio Rodrigues Ferreira Seiva, Maria Luisa Gonçalves Agneis, Matheus Ribas de Almeida, Wesley Ladeira Caputo, Milena Cremer de Souza, Karoliny Alves das Neves, Érika Novais Oliveira, Luis Antônio Justulin, and Luiz Gustavo de Almeida Chuffa
    MDPI AG
    Carcinogenesis is driven by complex molecular events, often involving key enzymes that regulate oxidative stress (OS). While classical enzymes such as SOD, catalase, and GPx have been extensively studied, other, non-classical oxidative stress-related enzymes (OSRE) may play critical roles in cancer progression. We aimed to explore the role of OSRE involved in an OS scenario and to assess their potential contribution to carcinogenesis in some of the most prevalent cancer types. Through data mining and bioinformatic analysis of gene and protein expression and mutation data, we identified OSRE with altered expression and mutations across cancer types. Functional pathways involving EGFR, MT-ND, GST, PLCG2, PRDX6, SRC, and JAK2 were investigated. Our findings reveal that enzymes traditionally considered peripheral to OS play significant roles in tumor progression. Those OSRE may contribute to cancer initiation and progression, as well as be involved with cancer hallmarks, such as EMT and invasion, proliferation, and ROS production. In addition, enzymes like SRC and JAK2 were found to have dual roles in both promoting ROS generation and being modulated by OS. OSRE also interact with key oncogenic signaling pathways, including Wnt/β-catenin and JAK2/STAT3, linking them to cancer aggressiveness and therapeutic resistance. Future research should focus on translating these findings into clinical applications, including the development of novel inhibitors or drugs targeting these non-classical enzymes.

  • Melatonin regulates endoplasmic reticulum stress in diverse pathophysiological contexts: A comprehensive mechanistic review
    Luiz Gustavo de Almeida Chuffa, Fábio Rodrigues Ferreira Seiva, Henrique S. Silveira, Roberta Carvalho Cesário, Karolina da Silva Tonon, Vinicius Augusto Simão, Debora Aparecida P. C. Zuccari, and Russel J. Reiter
    Wiley
    AbstractThe endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded protein response (UPR), which can either restore cellular homeostasis or induce cell death. Melatonin, a safe and multifunctional compound, shows promise in controlling ER stress and could be a valuable therapeutic agent for managing the UPR. By regulating ER and mitochondrial functions, melatonin helps maintain cellular homeostasis via reduction of oxidative stress, inflammation, and apoptosis. Melatonin can directly or indirectly interfere with ER‐associated sensors and downstream targets of the UPR, impacting cell death, autophagy, inflammation, molecular repair, among others. Crucially, this review explores the mechanistic role of melatonin on ER stress in various diseases including liver damage, neurodegeneration, reproductive disorders, pulmonary disease, cardiomyopathy, insulin resistance, renal dysfunction, and cancer. Interestingly, while it alleviates the burden of ER stress in most pathological contexts, it can paradoxically stimulate ER stress in cancer cells, highlighting its intricate involvement in cellular homeostasis. With numerous successful studies using in vivo and in vitro models, the continuation of clinical trials is imperative to fully explore melatonin's therapeutic potential in these conditions.

  • Maternal protein restriction combined with postnatal sugar consumption alters liver proteomic profile and metabolic pathways in adult male offspring rats
    Isabelle Tenori Ribeiro, Matheus Naia Fioretto, Sérgio Alexandre Alcantara dos Santos, Ketlin Thassiani Colombelli, Luiz Marcos Frediani Portela, Marcus Vinicius Niz Alvarez, Pedro de Magalhães Padilha, Aislan Quintiliano Delgado, Marcus Vinicius Lage Silva Giaculi Marques, José Roberto Bosqueiro,et al.
    Elsevier BV

  • Melatonin changes energy metabolism and reduces oncogenic signaling in ovarian cancer cells
    Henrique Spaulonci Silveira, Roberta Carvalho Cesário, Renan Aparecido Vígaro, Leticia Barbosa Gaiotte, Maira Smaniotto Cucielo, Fernando Guimarães, Fábio Rodrigues Ferreira Seiva, Debora Aparecida P.C. Zuccari, Russel J. Reiter, and Luiz Gustavo de Almeida Chuffa
    Elsevier BV


  • Unraveling the impact of melatonin treatment: Oxidative stress, metabolic responses, and morphological changes in HuH7.5 hepatocellular carcinoma cells
    Juliana M.B. de Morais, Ellen M.S. Cruz, Virgínia M. Concato, Milena C. de Souza, Yasmin M. Santos, Débora H. Quadreli, Fabrício S.R. Inoue, Francielle B. Ferreira, Glaura S.A. Fernandes, Danielle L. Bidóia,et al.
    Elsevier BV

  • Comprehensive Profiling and Therapeutic Insights into Differentially Expressed Genes in Hepatocellular Carcinoma
    Wesley Ladeira Caputo, Milena Cremer de Souza, Caroline Rodrigues Basso, Valber de Albuquerque Pedrosa, and Fábio Rodrigues Ferreira Seiva
    MDPI AG
    Background: Drug repurposing is a strategy that complements the conventional approach of developing new drugs. Hepatocellular carcinoma (HCC) is a highly prevalent type of liver cancer, necessitating an in-depth understanding of the underlying molecular alterations for improved treatment. Methods: We searched for a vast array of microarray experiments in addition to RNA-seq data. Through rigorous filtering processes, we have identified highly representative differentially expressed genes (DEGs) between tumor and non-tumor liver tissues and identified a distinct class of possible new candidate drugs. Results: Functional enrichment analysis revealed distinct biological processes associated with metal ions, including zinc, cadmium, and copper, potentially implicating chronic metal ion exposure in tumorigenesis. Conversely, up-regulated genes are associated with mitotic events and kinase activities, aligning with the relevance of kinases in HCC. To unravel the regulatory networks governing these DEGs, we employed topological analysis methods, identifying 25 hub genes and their regulatory transcription factors. In the pursuit of potential therapeutic options, we explored drug repurposing strategies based on computational approaches, analyzing their potential to reverse the expression patterns of key genes, including AURKA, CCNB1, CDK1, RRM2, and TOP2A. Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. Conclusion: This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.

  • New approaches concerning the testis of Astyanax lacustris (Characidae): immunohistochemical studies
    Fabiano Gonçalves Costa, Chayrra Chehade Gomes, Mateus Contar Adolfi, Mayra Costa da Cruz Gallo de Carvalho, Marco Antônio Zanoni, Fábio Rodrigues Ferreira Seiva, and Maria Inês Borella
    Springer Science and Business Media LLC

  • Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential
    Ellen Mayara Souza Cruz, Virginia Marcia Concato, Juliana Maria Bitencourt de Morais, Taylon Felipe Silva, Fabricio Seidy Ribeiro Inoue, Milena de Souza Cremer, Danielle Lazarin Bidóia, Rayanne Regina Beltrame Machado, Luiz Gustavo de Almeida Chuffa, Mário Sérgio Mantovani,et al.
    Elsevier BV

  • Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation
    M. Cucielo, R. C. Cesário, H. S. Silveira, L. B. Gaiotte, S. A. A. Dos Santos, D. A. P. de Campos Zuccari, F. Seiva, R. Reiter and L. G. de Almeida Chuffa

    Ovarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin). Intracellular melatonin levels increased after treatment with melatonin independent of the MT1. The mitochondrial membrane potential of SKOV-3 cells decreased in the group treated with the highest melatonin concentration. Melatonin reduced cellular glucose consumption, while MT1 knockdown increased its consumption. Interconversion of lactate to pyruvate increased after treatment with melatonin and was remarkable in siRNA MT1 groups. Moreover, lactate dehydrogenase activity decreased with melatonin and increased after MT1 silencing at all concentrations. The UCSC XenaBrowser tool showed a positive correlation between the human ASMTL gene and the ATP synthase genes, succinate dehydrogenase gene (SDHD), and pyruvate dehydrogenase genes (PDHA and PDHB). We conclude that melatonin changes the glycolytic phenotype and mitochondrial integrity of SKOV-3 cells independent of the MT1 receptor, thus decreasing the survival advantage of OC cells.

  • Hepatocellular carcinoma and miRNAs: An in silico approach revealing potential therapeutic targets for polyphenols
    Luiz Gustavo de Almeida Chuffa, Milena Cremer de Souza, Ellen Mayara Souza Cruz, Francielle Belinelli Ferreira, Juliana Maria Bitencourt de Morais, and Fábio Rodrigues Ferreira Seiva
    Elsevier BV

  • The proteomic landscape of ovarian cancer cells in response to melatonin
    Roberta Carvalho Cesário, Leticia Barbosa Gaiotte, Maira Smaniotto Cucielo, Henrique Spaulonci Silveira, Lucilene Delazari dos Santos, Debora Aparecida Pires de Campos Zuccari, Fábio Rodrigues Ferreira Seiva, Russel J. Reiter, and Luiz Gustavo de Almeida Chuffa
    Elsevier BV

  • Voluntary Exercise Attenuates Hyperhomocysteinemia, But Does not Protect Against Hyperhomocysteinemia-Induced Testicular and Epididymal Disturbances
    Dayane Priscila dos Santos, Diogo Farias Ribeiro, Giovanna Fachetti Frigoli, Rafaela Pires Erthal, Suellen Ribeiro da Silva Scarton, Glaucia Eloísa Munhoz de Lion Siervo, Fábio Rodrigues Ferreira Seiva, Larissa Staurengo-Ferrari, Waldiceu Aparecido Verri, Rafael Deminice,et al.
    Springer Science and Business Media LLC
    The hyperhomocysteinemia (HHcy) is toxic to the cells and associated with several diseases. Clinical studies have shown changes in plasma concentrations of Hcy after physical exercise. This study aimed to assess the effect of HHcy on testis, epididymis and sperm quality and to investigate whether voluntary exercise training protects this system against damage caused by HHcy in Swiss mice. In this study, 48 mice were randomly distributed in the control, HHcy, physical exercise, and HHcy combined with physical exercise groups. HHcy was induced by daily administration of dl-homocysteine thiolactone via gavage throughout the experimental period. Physical exercise was performed through voluntary running on the exercise wheels. The plasma concentrations of homocysteine (Hcy) and testosterone were determined. The testes and epididymis were used to assess the sperm count, histopathology, lipoperoxidation, cytokine levels, testicular cholesterol, myeloperoxidase, and catalase activity. Spermatozoa were analyzed for morphology, acrosome integrity, mitochondrial activity, and motility. In the testes, HHcy increased the number of abnormal seminiferous tubules, reduced the tubular diameter and the height of the germinal epithelium. In the epididymis, there was tissue remodeling in the head region. Ultimately, voluntary physical exercise training reduced plasma Hcy concentration but did not attenuate HHcy-induced testicular and epididymal disturbances.

  • Melatonin-loaded nanocarriers: New horizons for therapeutic applications
    Luiz Gustavo de Almeida Chuffa, Fábio Rodrigues Ferreira Seiva, Adriana Alonso Novais, Vinícius Augusto Simão, Virna Margarita Martín Giménez, Walter Manucha, Debora Aparecida Pires de Campos Zuccari, and Russel J. Reiter
    MDPI AG
    The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (N-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and non-metallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention.

  • Pterostilbene influences glycemia and lipidemia and enhances antioxidant status in the liver of rats that consumed sucrose solution
    Juliana Maria Bitencourt de Morais, Ellen Mayara Souza Cruz, Carlos Vinícius Dalto da Rosa, Roberta Carvalho Cesário, Jurandir Fernando Comar, Carolina Campos Lima Moreira, Luiz Gustavo de Almeida Chuffa, and Fábio Rodrigues Ferreira Seiva
    Elsevier BV
    AIMS The present study investigated the potential effects of pterostilbene (PT) on glycemic and lipid profiles, fat storage, cardiovascular indices, and hepatic parameters of rats fed with sucrose solution. MAIN METHODS 24 male Wistar rats received either drinking water or a 40% sucrose solution over a period of 140 days. After this period, animals were randomly allocated into four groups (n = 6): Control (C), C + Pterostilbene (PT), Sucrose (S), and S + PT. Pterostilbene (40 mg/kg) was given orally for 45 consecutive days. KEY FINDINGS Pterostilbene did not influence morphometric and nutritional parameters. The insulin sensitivity index TyG was elevated in the C + PT group (p < 0.01) and reduced in S + PT group (p < 0.05). Basal glucose levels were lower in the S + PT group (p < 0.05), and the glycemic response was improved with PT treatment in a glucose provocative test. Conversely, rats from the C + PT group showed impaired glucose disposal after during those tests. Lipid profile was partially improved by PT treatment. Hepatic oxidative stress in the S group was improved after PT treatment. In the C group, PT reduced SOD activity, glutathione levels, and increased catalase activity. Collagen content was reduced by PT treatment. SIGNIFICANCE PT effects depends on the type of diet the animals were submitted. In rats fed with sucrose-solution, PT confirmed its positive effects, improving glucose and lipid profile, and acting as a potent antioxidant. The effects of PT on rats that consumed a normal diet were very discrete or even undesirable. We suggest caution with indiscriminate consume of natural compounds by healthy subjects.

  • COVID-19: The question of genetic diversity and therapeutic intervention approaches
    David Livingstone Alves Figueiredo, João Paulo Bianchi Ximenez, Fábio Rodrigues Ferreira Seiva, Carolina Panis, Rafael dos Santos Bezerra, Adriano Ferrasa, Alessandra Lourenço Cecchini, Alexandra Ivo de Medeiros, Ana Marisa Fusco Almeida, Anelisa Ramão,et al.
    FapUNIFESP (SciELO)
    Abstract Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China’s Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients’ overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

  • A meta-analysis of microRNA networks regulated by melatonin in cancer: Portrait of potential candidates for breast cancer treatment
    Luiz Gustavo de Almeida Chuffa, Robson Francisco Carvalho, Luis Antônio Justulin, Sarah Santiloni Cury, Fábio Rodrigues Ferreira Seiva, Bruna Victorasso Jardim‐Perassi, Debora Aparecida Pires de Campos Zuccari, and Russel J. Reiter
    Wiley
    Melatonin is a ubiquitous molecule with a broad spectrum of functions including widespread anti‐cancer activities. Identifying how melatonin intervenes in complex molecular signaling at the gene level is essential to guide proper therapies. Using meta‐analysis approach, herein we examined the role of melatonin in regulating the expression of 46 microRNAs (miRNAs) and their target genes in breast, oral, gastric, colorectal, and prostate cancers, and glioblastoma. The deregulated miRNA‐associated target genes revealed their involvement in the regulation of cellular proliferation, differentiation, apoptosis, senescence, and autophagy. Melatonin changes the expression of miRNA‐associated genes in breast, gastric, and oral cancers. These genes are associated with cellular senescence, the hedgehog signaling pathway, cell proliferation, p53 signaling, and the hippo signaling pathway. Conversely, colorectal and prostate cancers as well as glioblastoma and oral carcinoma present a clear pattern of less pronounced changes in the expression of miRNA‐associated genes. Most notably, colorectal cancer displayed a unique molecular change in response to melatonin. Considering breast cancer network complexity, we compared the genes found during the meta‐analysis with RNA‐Seq data from breast cancer‐bearing mice treated with melatonin. Mechanistically, melatonin upregulated genes associated with immune responses and apoptotic processes, whereas it downregulated genes involved in cellular aggressiveness/metastasis (eg, mitosis, telomerase activity, and angiogenesis). We further characterized the expression profile of our gene subsets with human breast cancer and found eight upregulated genes and 16 downregulated genes that were appositively correlated with melatonin. Our results pose a multi‐dimension network of tumor‐associated genes regulated by miRNAs potentially targeted by melatonin.

  • The role of Toll-like receptor 4 signaling pathway in ovarian, cervical, and endometrial cancers
    Luiz Antonio Lupi, Maira Smaniotto Cucielo, Henrique Spaulonci Silveira, Letícia Barbosa Gaiotte, Roberta Carvalho Cesário, Fábio Rodrigues Ferreira Seiva, and Luiz Gustavo de Almeida Chuffa
    Elsevier BV
    Toll-like receptors (TLRs) are critical sensors related to inflammation and tumorigenesis. Among all subtypes, the TLR4 is a highly described transmembrane protein involved in the inflammatory process. The TLR4/myeloid differentiation factor 88 (MyD88) signaling pathway has been implicated in oncogenic events in several tissues and is associated with survival of patients. Through activation, TLR4 recruits adaptor proteins, i.e., MyD88 or TRIF, to triggers canonical and non-canonical signaling pathways that result in distinct immune responses. In most cancer cells, uncontrolled TLR4 signaling modifies the tumor microenvironment to proliferate and evade immune surveillance. By contrast, TLR4 activation can produce antitumor activities, thereby inhibiting tumor growth and enhancing the proper immune response. We review herein recent approaches on the role of the TLR4 signaling pathway and discuss potential candidates for gynecological cancer therapies; among these agents, natural and synthetic compounds have been tested both in vitro and in vivo. Since TLR4 ligands have been investigated as effective immune-adjuvants in the context of these aggressive malignancies, we described how TLR4 signaling controls part of the tumor-related inflammatory process and which are the new targeting molecules implicated in the regulation of tumorigenicity in ovarian, cervical, and endometrial cancers.

  • Long-term sucrose solution consumption causes metabolic alterations and affects hepatic oxidative stress in Wistar rats
    Ellen Mayara Souza Cruz, Juliana Maria Bitencourt de Morais, Carlos Vinícius Dalto da Rosa, Mellina da Silva Simões, Jurandir Fernando Comar, Luiz Gustavo de Almeida Chuffa, and Fábio Rodrigues Ferreira Seiva
    The Company of Biologists
    ABSTRACT As the number of overweight and obese people has risen in recent years, there has been a parallel increase in the number of people with metabolic syndrome, diabetes and non-alcoholic fatty liver disease. The consumption of artificially sweetened beverages contributes to these epidemics. This study investigated the long-term effects of ingestion of a 40% sucrose solution on serum and hepatic parameters in male Wistar rats (Rattus norvegicus). After 180 days, the glycemic response, lipid profile and hepatic oxidative stress were compared to those of rats maintained on water. Sucrose ingestion led to higher body weight, increased fat deposits, reduced voluntary food intake and reduced feeding efficiency. Rats that received sucrose solution showed early signs of glucose intolerance and insulin resistance, such as hyperinsulinemia. Serum triacylglycerol (TG), very-low density lipoprotein (VLDL), cholesterol, ALT and AST levels increased after sucrose consumption. Elevated malondialdehyde and superoxide dismutase (SOD) levels and reduced glutathione levels characterize the hepatic oxidative stress due to sucrose ingestion. Liver sample histology showed vacuolar traces and increased fibrotic tissue. Our data showed the harmful effects of chronic consumption of sucrose solution, which can cause alterations that are found frequently in obesity, glucose intolerance and non-alcoholic hepatic disease, characteristics of metabolic syndrome. Summary: Sucrose consumption in liquid form predisposes rats to obesity, alters glycemic and lipid profiles, and impairs hepatic oxidative metabolism; hence, we caution against excessive consumption of artificially-sweetened beverages.

  • Melatonin promotes uterine and placental health: Potential molecular mechanisms
    Luiz Gustavo de Almeida Chuffa, Luiz Antonio Lupi, Maira Smaniotto Cucielo, Henrique Spaulonci Silveira, Russel J. Reiter, and Fábio Rodrigues Ferreira Seiva
    MDPI AG
    The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the “receptivity window”. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine–placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.

  • Alcohol extract of Bauhinia forficata link reduces lipid peroxidation in the testis and epididymis of adult Wistar rats
    Carolina Ferreira Sampaio, Nicla Renata Lucchetta, Ana Paula Franco Punhagui, Philippe Rodrigues Banedetti, Nilton Syogo Arakawa, Fábio Rodrigues Ferreira Seiva, and Glaura Scantamburlo Alves Fernandes
    Wiley
    Bauhinia forficata is a medicinal plant that has flavonoid components with hypoglycemic, antioxidant, hepatoprotective, antibacterial, antiviral and anti‐inflammatory action. Aim of this study is to evaluate the action of B. forficata alcoholic extract in the male genital system of adult male Wistar rats. For that, 20 adult male Wistar rats were distributed into two experimental groups: the B. forficata group, receiving B. forficata alcoholic extract (0.1 ml/10 g body weight/day) on alternate days, and the control group, receiving just the vehicle for 30 days straight both via gavage. On the 31st day, the animals were euthanized, and the testis and epididymis were collected for histopathological, biochemical, morphometric, and sperm count analysis. Mass spectrometry identified new compounds in the extract: trans‐caffeic acid, liquiritigenin, gallocatechin, and 2,4,6‐trihydroxyphenanthren‐2‐glycoside. Biochemical analysis showed higher total cholesterol levels in the testis and lower malondialdehyde levels in the testis and epididymis, in the B. forficata group. The mast cell count showed a reduction in degranulated mast cells in the caput region of the epididymis, in the B. forficata group. The luminal compartment of the caput and the epithelial of the epididymis cauda were reduced, whereas the stromal region of the epididymis caput was increased in the B. forficata group, compared with the control group. The testicular tissue was less impaired, considering that all the histological analyses were similar to the control. We believe that B. forficata alcoholic extract in the male genital system showed antioxidant action, especially in the epididymal tissue.

  • Mitochondrial functions and melatonin: a tour of the reproductive cancers
    Luiz Gustavo de Almeida Chuffa, Fábio Rodrigues Ferreira Seiva, Maira Smaniotto Cucielo, Henrique Spaulonci Silveira, Russel J. Reiter, and Luiz Antonio Lupi
    Springer Science and Business Media LLC
    Cancers of the reproductive organs have a strong association with mitochondrial defects, and a deeper understanding of the role of this organelle in preneoplastic–neoplastic changes is important to determine the appropriate therapeutic intervention. Mitochondria are involved in events during cancer development, including metabolic and oxidative status, acquisition of metastatic potential, resistance to chemotherapy, apoptosis, and others. Because of their origin from melatonin-producing bacteria, mitochondria are speculated to produce melatonin and its derivatives at high levels; in addition, exogenously administered melatonin accumulates in the mitochondria against a concentration gradient. Melatonin is transported into tumor cell by GLUT/SLC2A and/or by the PEPT1/2 transporters, and plays beneficial roles in mitochondrial homeostasis, such as influencing oxidative phosphorylation and electron flux, ATP synthesis, bioenergetics, calcium influx, and mitochondrial permeability transition pore. Moreover, melatonin promotes mitochondrial homeostasis by regulating nuclear DNA and mtDNA transcriptional activities. This review focuses on the main functions of melatonin on mitochondrial processes, and reviews from a mechanistic standpoint, how mitochondrial crosstalk evolved in ovarian, endometrial, cervical, breast, and prostate cancers relative to melatonin’s known actions. We put emphasis on signaling pathways whereby melatonin interferes within cancer-cell mitochondria after its administration. Depending on subtype and intratumor metabolic heterogeneity, melatonin seems to be helpful in promoting apoptosis, anti-proliferation, pro-oxidation, metabolic shifting, inhibiting neovasculogenesis and controlling inflammation, and restoration of chemosensitivity. This results in attenuation of development, progression, and metastatic potential of reproductive cancers, in addition to lowering the risk of recurrence and improving the life quality of patients.

  • Effects of Bauhinia forficata on glycaemia, lipid profile, hepatic glycogen content and oxidative stress in rats exposed to Bisphenol A
    Mariane S. Pinafo, Philippe R. Benedetti, Letícia B. Gaiotte, Fabiano G. Costa, João Paulo F. Schoffen, Glaura S.A. Fernandes, Luiz Gustavo A. Chuffa, and Fábio R.F. Seiva
    Elsevier BV
    Graphical abstract