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Abstract Several countries and non-governmental organizations have discussed the use of animals in industry and biomedical areas. This work shows the progression of animal’ rights for scientific purposes in Brazil and how Brazilian Councils have advanced to follow worldwide regulations. Since the first rules about animals’ usage in Ireland in 1635, the British Cruelty to Animals Act in 1876, and the Brazilian animal protection rules in 1924 and 1934, most worldwide actions culminated in the Universal Declaration of Animal Rights (1978). In 1979, the Brazilian Law 6.638 displayed directives for didactic-scientific practice of vivisection. In 2008, the Arouca Law 11.794 filled regulatory gaps and created the National Council for the Control of Animal Experimentation (CONCEA). In 2014, the CONCEA incorporated the 3R’s philosophy and recognized substitute techniques, but only in 2023 it prohibited vertebrate animals in scientific research, development and control of personal hygiene products, cosmetics and perfumes. It is clear current Brazilian and international rules are unable to cover all aspects of animal wellbeing, even for regulations of commercial issues. Certainly, innovative tools, as organ-on-chip, in vitro techniques and bioinformatical advancements will provide a crucial animal welfare and new laws will minimize animal pain and distress, including for disregarded invertebrates.

Cancer is the second most common cause of death in the USA. Among the known classes of anticancer agents, the microtubule-targeted antimitotic drugs are considered to be one of the most important. They are usually classified into microtubule-destabilizing (e.g., Vinca alkaloids) and microtubule-stabilizing (e.g., paclitaxel) agents. Combretastatin A4 (CA-4), which is a natural stilbene isolated from Combretum caffrum, is a microtubule-destabilizing agent that binds to the colchicine domain on β-tubulin and exhibits a lower toxicity profile than paclitaxel or the Vinca alkaloids. In this paper, we describe the docking study, synthesis, antiproliferative activity and selectivity index of the N-acylhydrazone derivatives (5a-r) designed as CA-4 analogues. The essential structural requirements for molecular recognition by the colchicine binding site of β-tubulin were recognized, and several compounds with moderate to high antiproliferative potency (IC50 values ≤18 µM and ≥4 nM) were identified. Among these active compounds, LASSBio-1586 (5b) emerged as a simple antitumor drug candidate, which is capable of inhibiting microtubule polymerization and possesses a broad in vitro and in vivo antiproliferative profile, as well as a better selectivity index than the prototype CA-4, indicating improved selective cytotoxicity toward cancer cells.

Abstract Background Babassu (Orbignya phalerata Mart.) is a palm tree well distributed in Latin America, whose fruit has a mesocarp and kernel used for human feeding, and empirically related to the treatment of gastritis, vaginitis, and wound healing. Main body of the abstract The activities attributed to babassu can guide new research on health applications and, for this reason, this study aimed to report in vitro and in vivo biological activities of O. phalerata constituents through a systematic review. Searches terms were applied in five world databases and the data from the publications were collected according to PICOS criteria, including the fruit component, concentration/dose, time of exposure, and comparative groups. All outcomes were reported and the most relevant outcomes were described by a narrative synthesis and a risk of bias assessment. A total of 28 in vitro (n = 15) and in vivo (n = 11) studies were included, and two showed both experimental designs. The studies were heterogeneous, with the predominance of metabolic analysis, wound and peptic ulcer healing, besides in vivo toxicity, among others. For in vitro analysis, antioxidant tests, cell viability and antimicrobial activity predominated. All in vivo ones used rodents. Meanwhile, tumor and non-tumor cell lines, bacteria strains, Leishmania amazonensis, Artemia salina, and antioxidant reactions were considered for in vitro protocols. Short conclusion The most frequent applications included mesocarp and kernel in a wide range of extracts, emulsions, and concentrations. Their low in vitro lethality and cytotoxicity, and no acute toxicity in vivo open possibilities for the development of long-term toxicity assays with repeated doses in rodents and interventions in clinical trials. Graphic abstract

Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12–39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.

(1) Background: Riparin-A presents several pharmacological activities already elucidated, such as antimicrobial modulator, antileishmania, anxiolytic, anti-inflammatory, antinociceptive, and antioxidant. Even with important bioactive effects, the applicability of Riparin-A is limited due to its low solubility in water, impairing its dissolution in biological fluids. Thus, the objective of this study was to develop a nanohybrid based on Riparin-A and Laponite to obtain a better dissolution profile and evaluate its cytotoxic potential. (2) Methods: The formation of a hybrid system was highlighted by X-ray powder diffraction, infrared spectroscopy, and thermal analysis. Solubility, dissolution, and cytotoxicity studies were performed; (3) Results: An increase in the solubility and aqueous dissolution rate of Riparin-A was observed in the presence of clay. Diffractometric analysis of the hybrid system suggests the amorphization of Riparin-A, and thermal analyses indicated attenuation of decomposition and melting of the Riparin-A after interaction with clay. Furthermore, the nanosystem did not exhibit cytotoxic activity on normal and tumorigenic lines. (4) Conclusions: These results are promising for the development of the Riparin-A/Laponite nanosystem for therapeutic purposes, suggesting an increase in the range of possible routes of administration and bioavailability of this bioactive compound.

Research background. Commercialization of Mauritia flexuosa (buriti) fruits in Brazil is at an early stage. Herein, we evaluate the nutritional value of pulp, peel and endocarp samples from buriti fruits, perform macroscopic and microscopic evaluations and analyze their physicochemical properties. Experimental approach. Size and mass, pH, sugar and protein contents, soluble/insoluble fiber, total titratable acidity and energy value of the samples were analyzed. Mineral profiling was performed by energy dispersive X-ray fluorescence spectrometry, and fatty acids and phytosterols were determined by gas chromatography-mass spectrometry. Samples were also submitted to differential scanning calorimetry coupled to a thermal analyzer, and microstructure, morphology, surface and viscosity were evaluated by scanning electron microscopy (SEM) and X-ray diffraction (XRD) with copper radiation. Rheological behavior was also studied. Results and conclusions. Lyophilized pulp had higher nutritional content of minerals, proteins, carbohydrates and energy than in natura pulp. Lyophilized pulp and its by-products showed suitable yields (>17.31%) and low aw, and potassium, manganese and monounsaturated fatty acid contents. Peels showed elevated amounts of saturated and polyunsaturated fatty acids and phytosterols (β-sitosterol and stigmasterol), and endothermic behavior. The reductions of calcium, magnesium and manganese ranging from 18.5 to 22.7% were observed following the lyophilization. Drying processes generated semi-crystalline powders. Both peels and endocarp contained higher amounts of insoluble fiber and lower contents of sugars. Similar results were obtained by microscopic morphological analysis, differential scanning calorimetry and XRD analysis. Pulp and endocarp exhibited pseudoplastic non-Newtonian behavior, and flow behavior index values were lower than 1, while peels presented dilatant behaviour. Thus, physicochemical and nutritional characterization of pulp and by-products, such as peels and endocarp, are essential to support scientific research and exploration of new sustainable products. Novelty and scientific contribution. Processing and conservation techniques, like lyophilization, maintain the good quality of nutritional contents and bioactive compounds of buriti whole fruits, and can be used to extend their shelf life, preserve alimentary characteristics and provide wider purposes and availability. Such parameters may generate income and food security for local and regional communities.

Cancer development has been directly related to oxidative stress. During chemotherapy, some cancer patients use dietary antioxidants to avoid nutritional deficiencies due to cancer treatment. Among the antioxidants consumed, there are vitamins, including retinyl palmitate (PR) and ascorbic acid (AA), which have the capacity to reduce free radicals formation, protect cellular structures and maintain the cellular homeostasis. This systematic review evaluated the antioxidant and antitumor mechanisms of retinol palmitate (a derivative of vitamin A) and/or ascorbic acid (vitamin C) in cancer-related studies. Ninety-seven (97) indexed articles in the databases PubMed and Science Direct, published between 2013 and 2017, including 23 clinical studies (5 for every single compound while 13 in interaction) and 74 non-clinical studies (37 for retinol palmitate, 36 for ascorbic acid and 1 in interaction) were considered. Antioxidant and antitumor effects, with controversies over dosage and route of administration, were observed for the test compounds in their isolated form or associated in clinical studies. Prevention of cancer risks against oxidative damage was seen in lower doses of retinol palmitate and/or vitamin C. However, at high doses, they can generate reactive oxygen species, cytotoxicity and apoptosis in test systems. Non-clinical studies using cell lines have allowed understanding the mechanisms related to antioxidants and antitumor effects of the isolated compounds, however, studies on vitamin interactions, acting as antioxidants and/or antitumor are still rare and controversial. More studies, mainly related to modulation of antineoplastic drugs are needed for understanding the risks and benefits of their use during treatment in order to achieve effectiveness in cancer therapy and patient’s quality of life.

The present work aimed to characterize the exopolysaccharide obtained from water kefir grains (EPSwk), a symbiotic association of probiotic microorganisms. New findings of the technological, mechanical, and biological properties of the sample were studied. The EPSwk polymer presented an Mw of 6.35 × 105 Da. The biopolymer also showed microcrystalline structure and characteristic thermal stability with maximum thermal degradation at 250 °C. The analysis of the monosaccharides of the EPSwk by gas chromatography demonstrated that the material is composed of glucose units (98 mol%). Additionally, EPSwk exhibited excellent emulsifying properties, film-forming ability, a low photodegradation rate (3.8%), and good mucoadhesive properties (adhesion Fmax of 1.065 N). EPSwk presented cytocompatibility and antibacterial activity against Escherichia coli and Staphylococcus aureus. The results of this study expand the potential application of the exopolysaccharide from water kefir as a potential clean-label raw material for pharmaceutical, biomedical, and cosmetic applications.

Background: [6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice. Methods: The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 μM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 μM) and hydrogen peroxide (85.33 μM) were used as positive controls. Results: [6]-Gingerol, especially at concentrations of 42.66 and 85.33 μM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with H2O2 (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress. Conclusions: Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis.

The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.

Gingerol - [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone; [6]-G) - is a phenolic compound with several pharmacological properties. Herein, the aim of the study was to evaluate the toxicogenic effects of [6]-G on Artemia salina nauplii, Allium cepa, HL-60 cell line and Sarcoma 180 (S-180) ascitic fluid cells.For toxic and genotoxic analysis, it was used [6]-G concentrations of 5, 10, 20 and 40 μg mL-1. For cytotoxic evaluation using the MTT test (3- [4,5-dimethyl-thiazol-2-yl] -2,5-diphenyl tetrazolium bromide), serial [6]-G dilutions (1.56–100 μg mL-1) were performed, and S-180, HL-60 and peripheral blood mononuclear cells (PBMC) were treated for 72 h. The IC50 of [6]-G were 1.14, 5.73 and 11.18 μg mL-1 for HL-60, S-180 and PBMC, respectively, indicating a possible selectivity against tumor cell lines. At higher concentrations (>10 μg mL−1), toxicity and genotoxicity were observed in the A. cepa test, especially at 40 μg mL−1. Mechanisms indicating apoptosis, such as toxicity, cytotoxicity and nuclear abnormalities (bridges, fragments, delays, loose chromosomes and micronuclei) suggest that [6]-G has potential for antitumor pharmaceutical formulations.

ABSTRACTCasearia sylvestris Swartz is a medicinal plant widely distributed in Brazil. It has anti-inflammatory, antiulcer and antitumor activities and is popularly used to treat snakebites, wounds, diarrhea, flu and chest colds. Its leaves are rich in oxygenated tricyclic cis-clerodane diterpenes, particulary casearins. Herein, we evaluated the antioxidant activities of a fraction with casearins (FC) isolated from C. sylvestrisand histological changes on the central nervous system and livers of Mus musculus mice. Firstly, in vitro studies (0.9, 1.8, 3.6, 5.4 and 7.2 μg/mL) revealed EC50 values of 3.7, 6.4 and 0.16 µg/mL for nitrite, hydroxyl radical and TBARS levels, respectively. Secondly, FC (2.5, 5, 10 and 25 mg/kg/day) was intraperitoneally administered to Swiss mice for 7 consecutive days. Nitrite levels in the hippocampus (26.2, 27.3, 30.2 and 26.6 µM) and striatum (26.3, 25.4, 34.3 and 27.5 µM) increased in all treated animals (P < 0.05). Lower doses dropped reduced glutathione, catalase and TBARS levels in the hippocampus and striatum. With the exception of this reduction in TBARS formation, FC displayed only in vitro antioxidant activity. Animals exhibited histological alterations suggestive of neurotoxicity and hepatotoxicity, indicating the need for precaution regarding the consumption of medicinal formulations based on Casearia sylvestris.

Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.

No Ocidente, o consumo de plantas medicinais vem aumentando substancialmente, onde cerca de 40% da população utiliza regularmente plantas medicinais e preparações fitoterápicas sob o rótulo de serem produtos inócuos ou seguros. Porém, na maioria das vezes, não há comprovação científica de suas propriedades farmacológicas e toxicológicas. O objetivo deste trabalho foi realizar um levantamento bibliográfico sobre as propriedades toxicológicas da Casearia sylvestris Swartz e coletar dados que fundamentem seu uso racional. Alguns estudos validam indicações terapêuticas clássicas da C. sylvestris como antidiarréico e no tratamento de ferimentos ofídicos, fundamentando seu uso empírico. Porém, poucos trabalhos relatam suas propriedades toxicológicas, havendo apenas abordagens limitadas em torno da Dose Letal 50% e da toxicidade aguda de seus constituintes. Até o presente momento, as pesquisas são insuficientes para garantir a segurança de preparações populares à base de C. sylvestris. Portanto, há necessidade de avaliar melhor seu perfil deletério, principalmente, no que diz respeito ao potencial tóxico de seus constituintes, assim como a sua capacidade lesiva sobre órgãos-alvos e sistemas orgânicos.

A tea made with the leaves or stem bark of Bauhinia pulchella Benth (Fabaceae) is used in the treatment of diabetes. Ethanol (EEF) and aqueous (EAF) extracts were obtained from the leaves and the antioxidant and citotoxic activities were tested, as well as quantify the content of flavonoids and phenolic compounds (TPC). EEF and EAF showed similar profiles by HPLC, with the presence of three compounds. Column chromatography reverse phase (C18) and Sephadex LH-20, followed by semi preparative HPLC-C18 of EAF resulted in three flavonoids. Their structures were identified by 1H and 13C NMR as myricitrin (1), quercitrin (2) and afzelin (3). In assay of determination of reactive substances to thiobarbituric acid (TBARS), with DPPH, ABTS and nitric oxide (NO•) free radicals, EAF showed antioxidant potential higher than the EEF. This is the first report of the occurrence of the flavonoids 1-3, in the species B. pulchella. EEF and EAF were inactive in the cytotoxicity assays. In short, the polar extracts from the leaves of B. pulchella proved to be promising sources of biomolecules phenolic, with antioxidant potential, which may, in the future, be used as chemical markers for species and validation of therapeutic use.

ABSTRACT Aniba riparia (Lauraceae) is an important medicinal plant found in the Amazon region and presents alkaloids of the type alkamide known as riparins. Riparin A is structurally represented as the fundamental core of all Amazon riparins. This work aimed to assess the in vitro antioxidant, antitumor and antileishmanial effects of riparin A. Riparin A presented weak antioxidant capacity by tecniques of DPPH• (EC50 of 296.2 μg mL-1) and ABTS•+ (EC50 of 450.1 μg mL-1), showed moderate activity against colon carcinoma (HCT-116: IC50 of 21.7 μg mL-1) and leishmanicidal activity on promastigotes of L. amazonensis (IC50 of 307.0 ± 79.6, 193.7 ± 44.3 and 81.8 ± 11.2 μg mL-1, respectively, after 24, 48 and 72 h of incubation). Then, in addition to its structural simplicity, riparin A revealed promising biological activities and remarkable in vitro leishmanicidal action, an important result in epidemiological point of view to control leishmaniasis in Brazil, including in the Amazon region.

Resumo Dois terços da população mundial vivem em áreas infestadas com mosquitos vetores da dengue, especialmente o Aedes aegypti. Este estudo realizou um levantamento de dados sobre casos de dengue no município de Picos, no Estado do Piauí, Brasil, entre os anos de 2007 e 2011, enfatizando alguns fatores envolvidos em sua transmissão. Os dados foram coletados no Centro de Zoonoses de Picos da Secretaria Municipal de Saúde e no Sistema de Informação da Febre Amarela e Dengue (SISFAD) do Programa Nacional do Controle da Dengue (PNCD). Durante os anos de 2007, 2008, 2009, 2010 e 2011, foram visitados, respectivamente, 116.301, 182.024, 181.892, 187.619 e 195.377 imóveis pelos agentes de controle de endemias (ACE). As residências foram os estabelecimentos com maior positividade para focos de larvas de Aedes aegypti (p

Resumo Objetivos Avaliar o perfil dos trabalhadores rurais do município de Picos, no Estado do Piauí e suas práticas e atitudes quanto à utilização de agrotóxicos. Métodos A coleta dos dados (n=159) foi realizada em Picos com levantamento de dados socioeconômicos, utilização de equipamentos de proteção individual (EPIs), armazenamento e destino das embalagens de agrotóxicos, toxicidade e risco ambiental. Resultados A maioria dos agricultores era do sexo feminino (63%), não concluiu o ensino fundamental (55,6%), tinha entre 31 e 50 anos (55,3%), com renda de até um salário mínimo (66%) e possuía água encanada (84,3%). Quanto ao uso, 64,1% (102) utilizavam agrotóxicos, principalmente na agricultura (86,3%). Eles obtiveram informações sobre essas substâncias com vizinhos (44,2%), liam o rótulo para utilizar o produto (64,8%), usavam agroquímicos devido à ação rápida (81,4%), compravam em casas agropecuárias (87,4%), sem receituário agronômico (92%) e armazenavam embalagens dentro da própria casa (33,6%). Mais da metade não usava EPIs (56,8%), embora considerassem os agrotóxicos prejudiciais à saúde humana (94,1%) e ao meio ambiente (80,4%), além de 15% (24 pessoas) terem sentido algum sintoma de envenenamento. Conclusões Os entrevistados, em sua maioria, usavam agrotóxicos inadequadamente, tinham baixa escolaridade e conheciam sobre os riscos individuais e coletivos aos quais estavam expostos, mas não usavam EPIs.

This study described the use of household insecticides in Picos (Piauí, Brazil), identify which are the most used types of insecticides and describes the incidence of poisoning and environmental awareness of the population. After home visits (n = 700), it was seen that the majority of respondents was represented by women (75%), with 31-55 years-old (49%), incomplete primary education (38.1%) and income between 1-2 earnings (64%). Most homes have between 1-3 residents (48%), 85% of the persons use insecticides mainly chosen in TV and radio and only 54% of them read the label before employing the product. The most used form of presentation is the aerosol (70.7%). Majority (79%) recognizes that insecticides are harmful to health, but 74% do not use any Personal Protective Equipment (PPE). Symptoms of toxicity were reported by 27% of people interviewed. Two women reported irritation, dizziness and respiratory problems and need for medical intervention and hospitalization. All interviewed discard the package as regular trash, since Picos does not has selective collection. In conclusion, most people use insecticides, know about the individual and collective risks to which they are exposed but do not use PPE, though they believe insecticides are toxic. It was noted that acquisition of knowledge does not necessarily result in behavioral changes, since learning does not translate into appropriate preventive attitudes and practices, emphasizing the requirement for awareness campaigns about toxicity and environmental risks, preparation of professionals and surveillance policy against indiscriminate sale.

Molecular epidemiological studies have identified several risk factors linking to the genes and external factors in the pathogenesis of breast cancer. In this sense, genetic instability caused by DNA damage and DNA repair inefficiencies are important molecular events for the diagnosis and prognosis of therapies. Therefore, the objective of this study was to analyze correlation between sociocultural, occupational, and lifestyle risk factors with levels of genetic instability in non-neoplastic cells of breast cancer patients. Total 150 individuals were included in the study that included 50 breast cancer patients submitted to chemotherapy (QT), 50 breast cancer patients submitted to radiotherapy (RT), and 50 healthy women without any cancer. Cytogenetic biomarkers for apoptosis and DNA damage were evaluated in samples of buccal epithelial and peripheral blood cells through micronuclei and comet assay tests. Elder age patients (61–80 years) had higher levels of apoptosis (catriolysis by karyolysis) and DNA damage at the diagnosis (baseline damage) with increased cell damage during QT and especially during RT. We also reported the increased frequencies of cytogenetic biomarkers in patients who were exposed to ionizing radiation as well as for alcoholism and smoking. QT and RT induced high levels of fragmentation (karyorrhexis) and nuclear dissolution (karyolysis) and DNA damage. Correlations were observed between age and karyorrhexis at diagnosis; smoking and karyolysis during RT; and radiation and karyolysis during QT. These correlations indicate that risk factors may also influence the genetic instability in non-neoplastic cells caused to the patients during cancer therapies.

Plant polysaccharides have been increasingly employed in the pharmaceutical, industrial, and food environments due to their versatile functional properties. In the present investigation, a heteropolysaccharide galactomannan (GAP) was extracted from Adenanthera pavonina L. seeds and characterized by physicochemical analyses to determine its thermal properties, photostability, antioxidant activity, and acute toxicity. GAP was characterized by FTIR, DSC, and TG. The photostability of GAP submitted to artificial UV irradiation was analyzed. Antioxidant activity was evaluated by the DPPH (2,2-diphenyl-1-1-picrylhydrazyl) free radical-scavenging method, while a bioassay method was carried out to study acute toxicity in Artemia salina L. Physical-chemical and functional characteristics of GAP support its potential role in the food and pharmaceutical industries. GAP was photostable under UV irradiation. In vitro GAP antioxidant evaluation showed that it bears free radical-scavenging activity for DPPH radicals. The median lethal concentration (LC50) of GAP was 239.4 mg∙mL−1, indicating that this biopolymer is nontoxic. Such results indicate that this biopolymer presents characteristics of neutrality, photostability, and nontoxicity that are commercially attractive.

Mimosa caesalpiniifolia is a native plant of the Brazilian northeast, and few studies have investigated its chemical composition and biological significance. This work describes the identification of the first chemical constituents in the ethanolic extract and fractions of M. caesalpiniifolia stem bark based on NMR, GC-qMS and HRMS analyses, as well as an assessment of their cytotoxic activity. GC-qMS analysis showed fatty acid derivatives, triterpenes and steroid substances and confirmed the identity of the chemical compounds isolated from the hexane fraction. Metabolite biodiversity in M. caesalpiniifolia stem bark revealed the differentiated accumulation of pentacyclic triterpenic acids, with a high content of betulinic acid and minor amounts of 3-oxo and 3β-acetoxy derivatives. Bioactive analysis based on total phenolic and flavonoid content showed a high amount of these compounds in the ethanolic extract, and ESI-(−)-LTQ-Orbitrap-MS identified caffeoyl hexose at high intensity, as well as the presence of phenolic acids and flavonoids. Furthermore, the evaluation of the ethanolic extract and fractions, including betulinic acid, against colon (HCT-116), ovarian (OVCAR-8) and glioblastoma (SF-295) tumour cell lines showed that the crude extract, hexane and dichloromethane fractions possessed moderate to high inhibitory activity, which may be related to the abundance of betulinic acid. The phytochemical and biological study of M. caesalpiniifolia stem bark thus revealed a new alternative source of antitumour compounds, possibly made effective by the presence of betulinic acid and by chemical co-synergism with other compounds.

Este trabalho avaliou o conhecimento dos alunos do Curso de Ciências Biológicas da Universidade Federal do Piauí, Campus Senador Helvídio Nunes de Barros sobre o Papilomavírus Humano (HPV). A maioria dos estudantes universitários (n=218) eram do sexo feminino (78%), com idade entre 17 e 34 anos (60%), onde 84% eram solteiros e com renda familiar entre 2-5 salários mínimos (64%). A partir dos resultados, verificou-se que 87% conhecem o HPV, 83% o consideram como uma DST, 68% acreditam que tanto o homem quanto a mulher pode transmitir e se infectar pelo HPV, 48% acreditam na possibilidade de transmissão vertical, 35% consideram que o HPV possa infectar genitálias, cabeça e pescoço, 60% dos universitários responderam que o exame laboratorial utilizado para a prevenção e detecção inicial da infecção é o Papanicolau. Em relação aos fatores de risco, 64% afirmaram ter vida sexual ativa, 50% iniciaram sua vida sexual entre 13 e 17 anos, 44% usam preservativo durante relações sexuais, 63% consomem bebidas alcoólicas e 94% não fumam. A maioria afirmou (64%) não existir vacina contra o HPV, 52% acreditam em uma relação entre o HPV e o câncer de colo uterino e 97% gostariam de ler mais informações sobre o HPV. Assim, verificou-se que os alunos universitários revelaram conhecimento primário sobre o HPV e sobre formas de prevenção da doença. No entanto, quase a metade dos entrevistados desconhece a gravidade da infecção ocasionada por HPV como causa elementar para o surgimento de cânceres de colo uterino.

ABSTRACT Human epidermal receptors (HER1/2/3/4) belong to the class of receptor-type tyrosine kinases. After binding a ligand, dimerization, it will ocurr activation of intracellular kinases after two-dimensional and cytoplasmic tail reciprocal transphosphorylation. This transphosphorylation recruits signaling pathways such as Ras/Raf/MEK/Erk1-2, PI3-K/AKT and JAK/STAT, which can affect the cell cycle, cytoskeleton reorganization, apoptosis, metastasis, differentiation, angiogenesis and transcription. HER deregulation is found in epithelial, mesenchymal and nervous neoplasms and is associated with poor prognosis and tumor severity. Since HER are promiscuous proteins when subjected to mutations, resultant modifications confer cellular metabolic superiority and activate complex, interconnected and overlapping networks of cytoplasmic signaling. Moreover, overexpression of HER1/2 is involved in tumor resistance to radiation and anti-hormone therapies. Indeed, HER2 expression is up to 100-fold higher in 25-30% of invasive breast cancers. These characteristics support the development of resistance to anti-HER1/2 chemotherapy such as monoclonal antibodies and tyrosine kinase inhibitors. Then, the challenges in research with HER-positive cancers include planning therapeutic strategies against known resistance mechanisms and identifying novel mechanisms as a way to overcome and control cell growth and malignant progression.

This study aimed to evaluate the effects of aqueous extracts of dried Phyllanthus niruri L. (stonebreaker) leaves on Allium cepa L. root meristem cells at four concentrations, 0.02 (usual concentration), 0.04, 0.06 and 0.08mg/mL and exposure times of 24 and 48 hours. For each concentration we used a group of five onion bulbs that were first embedded in distilled water and then transferred to their respective concentrations. The radicles were collected and fixed in acetic acid (3:1) for 24 hours. The slides were prepared by the crushing technique and stained with 2% acetic orcein. Cells were analyzed throughout the cell cycle, totaling 5000 for each control and exposure time. The calculated mitotic indices were subjected to the Chi-squared statistical analysis (p

Folk uses and scientific investigations have highlighted the importance of Casearia sylvestris extracts and their relevant bioactive potential. The aim of this work was to review the pharmacological properties of C. sylvestris, emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor potentialities. Ethanolic extracts and essential oil of their leaves have antiulcerogenic activity and reduce gastric volume without altering the stomach pH, which corroborates their consumption on gastrointestinal disorders. Leaf water extracts show phospholipase A2 inhibitory activity that prevents damage effects on the muscular tissue after toxin inoculation. This antiphospholipasic action is probably related to the use as an anti-inflammatory, proposing a pharmacological blockage similar to that obtained with non-steroidal anti-inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided-assay fractionations lead to the identification of secondary metabolites, especially the clerodane diterpenes casearins (A-X) and casearvestrins (A-C), compounds with a remarkable cytotoxic and antitumor action. Therefore, the C. sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive folk utilization, exciting searches for new molecules and a better comprehension about biological properties.Usos populares e pesquisas científicas têm destacado a importância dos extratos da planta Casearia sylvestris e seu grande potencial bioativo. Neste trabalho, objetiva-se revisar as propriedades farmacológicas de C. sylvestris, enfatizando sua potencialidade antiulcerogênica, antiinflamatória, antiofídica e antitumoral. O extrato etanólico e o óleo essencial das folhas possuem atividade antiulcerogênica promissora, diminuindo o volume gástrico sem alterar o pH estomacal, corroborando sua aplicação contra dores gastrointestinais. Já os extratos aquosos das folhas têm atividade inibitória contra fosfolipase A2 presente em venenos de cobras, atenuando os efeitos lesivos sobre a musculatura esquelética resultantes da inoculação das toxinas. Essa ação antifosfolipásica provavelmente está relacionada ao seu uso como antiinflamatório, sugerindo um bloqueio análogo ao dos fármacos antiinflamatórios não-esteroidais na formação de mediadores oriundos do ácido araquidônico e na ativação da ciclooxigenase. Ensaios de fracionamento bioguiado dos extratos culminaram no isolamento e identificação de inúmeros metabólitos secundários, especialmente os diterpenos clerodânicos casearinas (A-X) e casearvestrinas (AC), compostos que têm surpreendido por sua ação citotóxica e antitumoral. Assim, a planta C. sylvestris apresenta um enorme arsenal farmacológico já mundialmente comprovado por seu vasto uso popular, estimulando pesquisas por novas moléculas e a busca pela compreensão de suas propriedades biológicas.

This study assessed the antiproliferative and cytotoxic potential against tumor lines of ethanolic seed extracts of 21 plant species belonging to different families from Northeastern Brazil. In addition, some underlying mechanisms involved in this cytotoxicity were also investigated. Among the 21 extracts tested, the MTT assay after 72 h of incubation demonstrated that only the ethanolic extract obtained from Myracrodruon urundeuva seeds (EEMUS), which has steroids, alkaloids and phenols, showed in vitro cytotoxic activity against human cancer cells, being 2-fold more active on leukemia HL-60 line [IC50 value of 12.5 (9.5-16.7) μg/mL] than on glioblastoma SF-295 [IC50 of 25.1 (17.3-36.3) μg/mL] and Sarcoma 180 cells [IC50 of 38.1 (33.5-43.4) μg/mL]. After 72h exposure, flow cytometric and morphological analyses of HL-60-treated cells showed that EEMUS caused decrease in cell number, volume and viability as well as internucleosomal DNA fragmentation in a dose-dependent way, suggesting that the EEMUS triggers apoptotic pathways of cell death.Este estudo avaliou o potencial antiproliferativo e citotóxico contra linhagens de células tumorais de extratos etanólicos de sementes de vinte e uma espécies vegetais pertencentes a diferentes famílias do Nordeste brasileiro. Além disso, alguns mecanismos subjacentes envolvidos nesta citotoxidade também foram investigados. Dentre os 21 extratos testados pelo ensaio do MTT após 72 h de incubação, apenas o extrato etanólico obtido a partir de sementes de Myracrodruon urundeuva (EEMUS), o qual apresentou traços de esteróides, alcalóides e fenóis em sua composição, demonstrou atividade citotóxica in vitro contra células tumorais humanas, sendo 2 vezes mais ativo sobre a linhagem leucêmica HL-60 [IC50 valor de 12,5 (9,5-16,7) μg/mL] do que sobre células de glioblastoma SF-295 [IC50 de 25,1 (17,3-36,3) μg/mL] e de sarcoma 180 [IC50 de 38,1 (33,5-43,4) μg/mL]. Após 72 h de exposição, as análises morfológicas e por citometria de fluxo de células HL-60 tratadas com EEMUS mostraram diminuição no número de células, seu volume e viabilidade, assim como fragmentação internucleosomal do DNA de forma dose-dependente, sugerindo que a ação antiproliferativa de EEMUS pode ser ativada por vias apoptóticas.

Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. The objectives of this work were to comparatively study the inhibitory action of antioxidants (ascorbic acid or α-tocopherol) on behavioral changes and brain damage induced by high doses of pilocarpine, aiming to further clarify the mechanism of action of these antioxidant compounds. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (250 or 500 mg/kg, i.p.) and α-tocopherol (200 or 400 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (400 mg/kg, i.p., P400 model) in rats. Ascorbic acid or α-tocopherol injections prior to pilocarpine suppressed behavioral seizure episodes. These findings suggested that free radicals can be produced during brain damage induced by seizures. In the P400 model, ascorbic acid and α-tocopherol significantly decreased cerebral damage percentage. Antioxidant compounds can exert neuroprotective effects associated with inhibition of free radical production. These results highlighted the promising therapeutic potential of ascorbic acid and α-tocopherol in treatments for neurodegenerative diseases.A epilepsia de lobo temporal é a mais comum forma de epilepsia em humanos. O estresse oxidativo é um dos mecanismos de morte celular induzida pelas crises convulsivas. Os compostos antioxidantes apresentam efeitos neuroprotetores devido à sua capacidade de inibir a produção de radicais livres. Os objetivos do presente trabalho foram estudar de forma comparativa a ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol) sobre as alterações comportamentais e histopatológicas no hipocampo de ratos após convulsões induzidas pela pilocarpina. A fim de determinar os efeitos neuroprotetores destas drogas, o presente trabalho estudou os efeitos do ácido ascórbico (250 ou 500 mg/kg, i.p.) e do α-tocoferol (200 ou 400 mg/kg, i.p.) sobre o comportamento e as lesões cerebrais observados após convulsões induzidas pela pilocarpina (400 mg/kg, i.p., P400), em ratos. As injeções de ácido ascórbico ou α-tocoferol antes da administração de pilocarpina reduzem o número de animais que convulsionam. Estes achados sugerem que os radicais livres podem induzir o desenvolvimento de lesão cerebral durante as crises epilépticas. No modelo P400, o ácido ascórbico e o α-tocoferol, diminuem significativamente os danos cerebrais. Os compostos antioxidantes podem exercer efeitos neuroprotetores, e esses resultados podem estar associados à inibição da produção de radicais livres. Estes resultados sugerem um promissor potencial terapêutico tanto para o ácido ascórbico quanto para o α-tocoferol no tratamento de doenças neurodegenerativas.

Propolis is mostly used as hydroalcoholic extract. Recently there has been a growing number of patents dealing with new solvents for preparing propolis extracts. This study aimed to prepare edible oil propolis extracts and compare their chemical composition and biological activity with ethanolic propolis extracts. ESI-MS and spectrophotometric methods were used for qualitative and quantitative analyses, respectively. Antibacterial activity was evaluated by diffusion in agar. Cytotoxicity was tested by MTT assay using tumor cell lines. The oil is able to extract bioactive compounds from propolis. Further studies are needed to improve extraction efficiency and to characterize the active components.