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1.
Biotechnol Appl Biochem ; 69(6): 2437-2444, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34837656

RESUMO

Hexachlorobenzene (HCB) is a pollutant still found in the environment despite being widely banned. Considering that basidiomycetes are useful to degrade a variety of organochlorinated pollutants, we therefore report the influence of HCB on the ligninolytic enzymatic system of Deconica castanella. The inoculum was prepared with sugarcane bagasse and soybean flour and was added in soil with and without HCB (2000 mg kg soil-1 ), 5% emulsion containing soybean oil and Tween 20 at proportion 9:1, v:v; with 70% moisture at 25°C. Fungal biomass was quantified by widely acknowledged growth biomarker ergosterol. The extraction of the enzymatic complex was performed and laccase, Mn-dependent peroxidase (MnP), and lignin peroxidase (LiP) activities were determined. Furthermore, HCB and its metabolites were quantified by gas chromatography and chlorides by potentiometric titration. Results evidenced that HCB did not interfere in fungal growth, though the only detected enzymatic activity was laccase. MnP and Lip were not detected during D. castanella growth in soil. The peak of laccase enzymatic activity occurred in the presence of HCB. In addition, the laccase exhibited thermostability. Therefore, we hereby shed light on the role of laccase in the degradation of HCB by an efficient low-cost and environmentally safe detoxification mechanism.


Assuntos
Basidiomycota , Poluentes Ambientais , Saccharum , Celulose , Lacase/metabolismo , Hexaclorobenzeno , Saccharum/metabolismo , Peroxidases/metabolismo , Basidiomycota/metabolismo , Lignina/metabolismo , Biodegradação Ambiental
2.
J Dev Orig Health Dis ; 12(4): 595-602, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33109301

RESUMO

Alterations in the circadian cycle are known to cause physiological disorders in the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal axes in adult individuals. Therefore, the present study aimed to evaluate whether exposure of pregnant rats to constant light can alter the reproductive system development of male offspring. The dams were divided into two groups: a light-dark group (LD), in which pregnant rats were exposed to an LD photoperiod (12 h/12 h) and a light-light (LL) group, in which pregnant rats were exposed to a photoperiod of constant light during the gestation period. After birth, offspring from both groups remained in the normal LD photoperiod (12 h/12 h) until adulthood. One male of each litter was selected and, at adulthood (postnatal day (PND) 90), the trunk blood was collected to measure plasma testosterone levels, testes and epididymis for sperm count, oxidative stress and histopathological analyses, and the spermatozoa from the vas deferens to perform the morphological and motility analyses. Results showed that a photoperiod of constant light caused a decrease in testosterone levels, epididymal weight and sperm count in the epididymis, seminiferous tubule diameter, Sertoli cell number, and normal spermatozoa number. Histopathological damage was also observed in the testes, and stereological alterations, in the LL group. In conclusion, exposure to constant light during the gestational period impairs the reproductive system of male offspring in adulthood.


Assuntos
Ritmo Circadiano , Genitália Masculina/crescimento & desenvolvimento , Luz/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Feminino , Genitália Masculina/patologia , Masculino , Estresse Oxidativo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos Wistar , Espermatogênese , Testosterona/sangue
3.
Oxid Med Cell Longev ; 2020: 3457890, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308801

RESUMO

Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.


Assuntos
Instabilidade Genômica/efeitos dos fármacos , Neoplasias/etiologia , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Animais , Humanos , Ratos
4.
Rio de Janeiro; Cebes; 2020. 223 p. il.
Monografia em Português | HISA - História da Saúde | ID: his-44390

RESUMO

A obra apresenta o IdeiaSUS e qual foi a motivação para a sua criação. Apresenta seis práticas premiadas e destaca outras ações realizadas nos sete anos. Traz reflexões dos vários atores envolvidos nessa construção, a ideia de que o compartilhamento é essencial ao SUS, significa apoiar e fortalecer o trabalho de gestores, profissionais, líderes comunitários, estudantes, pesquisadores e usuários da saúde pública brasileira


Assuntos
Sistema Único de Saúde , Saúde Pública , Atenção à Saúde
5.
Toxicol Appl Pharmacol ; 380: 114692, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31356931

RESUMO

Arylacetamides are widely used as synthetic intermediates to obtain medicinal substances. This work evaluated in vitro antiproliferative activity of ten 2-Chloro-N-arylacetamides on human normal and cancer cells and detailed in vivo toxicological and anticancer investigations. Initially, cytotoxic colorimetric assays were performed using tumor lines, peripheral blood mononuclear cells (PBMC) and erythrocytes. Compounds 2, 3 and 4 were tested for acute toxicity (50, 150 and 300 mg/kg) and for subacute antitumoral capacity in HCT-116 colon carcinoma-bearing xenograft mice for 15 days at 25 mg/kg/day. Most compounds revealed cytotoxic action on tumor lines and PBMC, but activity on human erythrocytes were not detected. Molecular dipole moment, lipophilicity and electronic constant of aryl substituents had effects upon in vitro antiproliferative capacity. More common in vivo acute behavioral signals with compounds 2, 3 and 4 were muscle relaxation, reduction of spontaneous locomotor activity and number of entries in closed arms and increased number of falls andtime spent in open arms, suggesting diazepam-like anxiolytic properties. Decrease of grabbing strength and overall activity were common, but palpebral ptosis and deaths occurred at 300 mg/kg only. Compounds 2 and 3 reduced colon carcinoma growth (21.2 and 27.5%, respectively, p < 0.05) without causing apparent signals of organ-specific toxicity after subacute exposure. The structural chemical simplicity of arylacetamides make them cost-effective alternatives and justifies further improvements to enhance activity, selectivity and the development of pharmaceutical formulations.


Assuntos
Acetamidas/uso terapêutico , Ansiolíticos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Acetamidas/farmacologia , Acetamidas/toxicidade , Adolescente , Adulto , Animais , Ansiolíticos/farmacologia , Ansiolíticos/toxicidade , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Camundongos , Adulto Jovem
6.
Prep Biochem Biotechnol ; 49(9): 908-915, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31271327

RESUMO

Pentachlorophenol (PCP) is an organochlorine pesticide whose toxicity led it to be banned in several countries. In Brazil however, this compound is widely accessible, and its indiscriminate use leads to extensive soil contamination, which requires henceforth, the development of new approaches to manage PCP presence in environment. Considering that PCP is susceptible to undergo enzymatic degradation, this investigation is thence, aimed at the purification, and characterization, of a thermostable fungal enzyme (i.e. Laccase of Deconica castanella (Dc-Lac), and assess its role in PCP in vitro biodegradation. Results evidenced that, molecular mass of the partially purified Dc-Lac was estimated to be of 64 kDa, presenting apparent Km of 0.47 µmol, and Vmax of 11.56 U mg-1. The optimum temperature and pH were 55 °C and 2.5, respectively. The T½ verified at 55, 60, and 80 °C were 19 and 17 hr, and 47 min, respectively. The highest PCP biodegradation was of 23% at pollutant concentration of 100 µg L-1, which evidenced that Dc-Lac is a thermostable enzyme that acted directly in PCP degradation and may be a useful asset to remediate this pollutant.


Assuntos
Agaricales/enzimologia , Poluentes Ambientais/metabolismo , Lacase/metabolismo , Pentaclorofenol/metabolismo , Praguicidas/metabolismo , Agaricales/química , Agaricales/metabolismo , Biodegradação Ambiental , Estabilidade Enzimática , Lacase/química , Temperatura
7.
J Physiol ; 597(15): 3905-3925, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31210356

RESUMO

KEY POINTS: Cancer growth, cell proliferation and cachexia index can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins in adolescence. Walker 256 tumour-bearing rats who started exercise training during adolescence did not revert the basal low glycaemia and insulinaemia observed before tumour cell inoculation. The moderate exercise training improved glucose tolerance and peripheral insulin sensitivity only in rats exercised early in adolescence. The chronic effects of our exercise protocol are be beneficial to prevent cancer cachexia and hold clear potential as a nonpharmacological therapy of insulin sensitization. ABSTRACT: We tested the hypothesis that moderate exercise training, performed early, starting during adolescence or later in life during adulthood, can inhibit tumour cell growth as a result of changes in biometric and metabolic markers. Male rats that were 30 and 70 days old performed a treadmill running protocol over 8 weeks for 3 days week-1 , 44 min day-1 and at 55-65% V̇O2max . After the end of training, a batch of rats was inoculated with Walker 256 carcinoma cells. At 15 days after carcinoma cell inoculation, the tumour was weighed and certain metabolic parameters were evaluated. The data demonstrated that physical performance was better in rats that started exercise training during adolescence according to the final workload and V̇O2max . Early or later moderate exercise training decreased the cachexia index, cell proliferation and tumour growth; however, the effects were more pronounced in rats that exercised during adolescence. Low glycaemia, insulinaemia and tissue insulin sensitivity was not reverted in Walker 256 tumour-bearing rats who trained during adolescence. Cancer growth can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins during adolescence. In addition, improvement in glucose-insulin homeostasis might be involved in this process.


Assuntos
Carcinoma 256 de Walker/terapia , Condicionamento Físico Animal/métodos , Animais , Caquexia/metabolismo , Caquexia/prevenção & controle , Carcinoma 256 de Walker/patologia , Carcinoma 256 de Walker/prevenção & controle , Células Cultivadas , Glucose/metabolismo , Resistência à Insulina , Masculino , Ratos , Ratos Wistar
8.
Appl Biochem Biotechnol ; 188(1): 282-296, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30430345

RESUMO

This study evaluates a correlation between family history, micronutrients intake, and alternative therapies with genetic instability, before and during breast cancer treatment. For this study, a total of 150 women were selected. Among those, 50 women were breast cancer patients on chemotherapy, while 50 breast cancer patients were on radiotherapy, and 50 were healthy females. All the participants signed the informed consent form and answered the public health questionnaire. Samples of buccal epithelial and peripheral blood cells were collected and analyzed through micronucleus and comet assays. The cells were evaluated for apoptosis and DNA damage. Results showed the association of patients' family history with an increase in toxicogenetic damage before and during cancer therapy. On the other hand, patients with late-onset cancer also presented genetic instability before and during therapy, along with those who did not take sufficient vegetables and alternative therapies. A positive correlation was observed between the genetic instability and alternative therapies, while inverse correlation was recorded with the vegetable consumption. Results clearly explain that the nutritional aspects and alternative therapies influence the genetic instability before and during cancer therapies especially in radiotherapy treated patients. Our data could be used for the monitoring therapies and management of breast cancer patients.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Terapias Complementares , Dieta , Instabilidade Genômica , Anamnese , Estudos de Casos e Controles , Ensaio Cometa , Feminino , Frutas , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Verduras
9.
Biomed Pharmacother ; 110: 68-73, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30466004

RESUMO

Agathisflavone (AGF) is a biflavonoid with a number of important biological and pharmacological activities, such as antioxidant, antimicrobial, and neuroprotective effects. However, its toxicological effects have not been fully investigated. Accordingly, the aim of this study was to investigate the toxicological effects of AGF in mice. For this purpose, the median lethal dose 50% (LD50) was determined along with the anatomic and histopathological parameters (weight, alimentation, excretion, biochemical, and hematological) in fertile untouched female Swiss mice. Results suggest that during the treatment, no deaths were reported at 300 and 2000 mg/kg (n = 03/group, p.o.). Moreover, AGF did not cause significant change in the above mentioned parameters in test animals when compared with the control group (0.05% Tween 80 dissolved in 0.9% saline). Taken all together, this non-clinical toxicological study revealed that AGF has an LD50 larger than 2000 mg/kg and did not change significantly the hematological, biochemical, histopathological, behavioral, as well as physiological parameters in the female mice.


Assuntos
Biflavonoides/toxicidade , Extratos Vegetais/toxicidade , Animais , Biflavonoides/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Dose Letal Mediana , Camundongos , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Teste de Desempenho do Rota-Rod/métodos
10.
Revista Poli ; 11(65): 14-21, jul./ago. 2019.
Artigo em Português | HISA - História da Saúde | ID: his-43377

RESUMO

Especialistas a revisitam a 8ª Conferência Nacional de Saúde, que inscreveu o SUS na Constituição Federal, e discutem expectativas para a 16ª edição do evento. (AU)


Assuntos
Conferências de Saúde , Direito à Saúde , Sistema Único de Saúde , Financiamento da Assistência à Saúde
11.
Oxid Med Cell Longev ; 2018: 2846819, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013718

RESUMO

This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient's cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.


Assuntos
Neoplasias da Mama/genética , Dano ao DNA/genética , Adulto , Células Cultivadas , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Testes para Micronúcleos , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos
12.
Chem Cent J ; 12(1): 75, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29959550

RESUMO

PURPOSE: Free radicals are considered as the causative agents of a variety of acute and chronic pathologies. Natural antioxidants have drawn attention of the researchers in recent years for their ability to scavenge free radicals with minimal or even no side effects. This study evaluates the antioxidant capacity of agathisflavone, a naturally occurring biflavonoid by a number of in vitro methods. METHODS: Agathisflavone was subjected to DPPH, ABTS, OH and NO radical scavenging assay, reducing potential and inhibition of lipid peroxidation (TBARS) test using trolox as a standard. RESULTS: Agathisflavone showed concentration-dependent antioxidant activity against all types of free radicals used in this study. The antioxidant capacity, reducing potential and inhibition of lipid peroxidation showed by agathisflavone were comparable to that of trolox. CONCLUSION: Agathisflavone exhibited antioxidant capacity, which suggests considering this biflavonoid for the use in the prevention and/or treatment of diseases precipitated by oxidative stress.

13.
Front Physiol ; 9: 465, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867528

RESUMO

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55-65% VO2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training did not cause injury or trigger inflammatory processes prior to tumor cell inoculation. Taken together, the current study suggests that aerobic exercise training applied during adolescence may mitigate tumor growth and related disorders in Walker 256 tumor-bearing adult rats. Improved insulin sensibility, lower glucose and insulin levels and/or reduced insulin secretion stimulated by glucose may be implicated in this tumor attenuation.

14.
Chem Biol Interact ; 289: 119-128, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29572072

RESUMO

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. In addition, the toxicity and antioxidant capacities were tested in Artemia salina and rat erythrocytes, respectively. The results suggest that, an acute administration of the IF at doses of 25, 50, 75 and 150 mg/kg (intraperitoneal, i.p.) significantly (p < 0.05) reduced the marble burying behavior of the animals as compared to the vehicle group, which demonstrates a calming effect of this chemical. It was observed that, the pre-treatment with flumazenil (2.5 mg/kg, i.p.), an antagonist of the gamma-amino butyrinc acid (GABAA) receptor, significantly reversed the marble burying behavioral activity in the animals treated with the IF 150 mg/kg dose. Moreover, the reduction in nitrite content and lipid peroxidation levels, while an increased in the reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16 mM) did not show toxicity in A. salina but exhibited a prominent antioxidant capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In conclusion, IF exhibited an anxiety-like effect in mice along with a potent antioxidant capacity, and we suppose it may have neuroprotective effects possibly via GABAergic transmission pathway.


Assuntos
Ansiolíticos/farmacologia , Biomarcadores/metabolismo , Ácidos Cumáricos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Animais , Antioxidantes/metabolismo , Artemia/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Ácidos Cumáricos/toxicidade , Diazepam/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hemólise/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Nitritos/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Testes de Toxicidade
15.
Regul Toxicol Pharmacol ; 92: 338-346, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29258925

RESUMO

ß-caryophyllene is a food additive that is found in food plants and has broad pharmacological potential. However, little toxicological information has been reported and its use is based on the fact that this bicyclic sesquiterpene is daily consumed as a plant food in much larger quantities than as a food additive. Thus, this study evaluated acute (14-day) and repeated-dose (28 days) oral ß-caryophyllene toxicity in female Swiss mice analyzing changes in body weight, food intake, water intake, hematological and biochemical parameters, organ weight after necropsy, oxidative stress markers and histopathology of various tissues. Acute (300 and 2000 mg/kg) and repeated-dose (300 and 2000 mg/kg) toxicity studies were performed according to the Organization for Economic Cooperation and Development (OECD) guideline 423 and 407, respectively. There was absence of adverse clinical signs and mortality in any animal subjected to acute and repeated-dose toxicity study. In addition, no significant changes in body weight, food and water intake, oxidative stress biomarkers, hematological and biochemical parameters were observed when compared to control group from single-dose and repeated-dose toxicity study. Therefore, the results of this study provide an understanding of the toxicity profile of ß-caryophyllene which can be considered a compound with toxicity at doses higher than 2000 mg/kg body weight.


Assuntos
Canabinoides/efeitos adversos , Sesquiterpenos/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Dieta , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Aditivos Alimentares/efeitos adversos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Sesquiterpenos Policíclicos , Testes de Toxicidade Aguda/métodos
16.
Toxicol Lett ; 285: 121-131, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29287997

RESUMO

Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure. Marinobufagin presented high antiproliferative action against all human tumor lines [IC50 values ranging from 0.15 (leukemia) to 7.35 (larynx) µM] and it failed against human erythrocytes and murine lines. Human normal peripheral blood mononuclear cells (PBMC) were up to 72.5-fold less sensitive [IC50: 10.88 µM] to marinobufagin than HL-60 line, but DNA strand breaks were no detected. Leukemia treaded cells exhibited cell viability reduction, DNA fragmentation, phosphatidylserine externalization, binucleation, nuclear condensation and cytoplasmic vacuoles. Marinobufagin also reduced the growth of A. cepa roots (EC50: 7.5 µM) and mitotic index, caused cell cycle arrest and chromosomal alterations (micronuclei, delays and C-metaphases) in meristematic cells. So, to find out partially targeted natural molecules on human leukemia cells, like marinobufagin, is an amazing and stimulating way to continue the battle against cancer.


Assuntos
Antineoplásicos/farmacologia , Bufanolídeos/farmacologia , Ciclo Celular/efeitos dos fármacos , Quebras de DNA , Cebolas/efeitos dos fármacos , Adolescente , Adulto , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/toxicidade , Bufanolídeos/isolamento & purificação , Bufanolídeos/toxicidade , Bufonidae/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Células HL-60 , Voluntários Saudáveis , Hemólise/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Meristema/citologia , Meristema/efeitos dos fármacos , Meristema/genética , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Cebolas/citologia , Cebolas/genética , Pele/metabolismo , Adulto Jovem
17.
J Cell Biochem ; 119(3): 2923-2928, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29120088

RESUMO

Chemotherapy is a standard treatment method for the patients with locally advanced breast cancer. Lately, cyclophosphamide (CYP) and doxorubicin (DOX) are used as the major chemotherapeutic agents especially for the treatment of breast cancer. Till date, no serum biomarker has been able to provide an early diagnosis of breast cancer. This study aimed to assess inflammatory, cardiac, renal and hematological markers in 56 breast cancer patients (BCP) before, during and after termination of chemotherapy with CYP and DOX. Blood samples were collected from the patients at the each treatment stages mentioned above. These samples were assessed for interleukin 6 (IL-6), interleukin 10 (IL-10), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine, hemoglobin (Hb), leukocyte, platelet and Na+ /K+ -ATPase levels either by ELISA or colorimetric methods. The results suggest a significant increase in IL-6 level at all the stages in BCP as compared to control group. On the other hand, IL-10, CK and Na+ /K+ -ATPase levels were found to be significantly declined during all the stages. Moreover, the majority of hematological parameters remained unchanged throughout the treatment period with the exception of creatinine and Hb which showed slight modulation in their level at different stages. Based on the results, we conclude that breast cancer and co-treatment with CYP and DOX, interfere arious biological markers, thereby, showing the physiological imbalance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Proteínas de Neoplasias/sangue , Doxorrubicina/administração & dosagem , Feminino , Humanos
18.
Birth Defects Res ; 109(16): 1292-1300, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-28762666

RESUMO

BACKGROUND: Pimenta pseudocaryophyllus (Gomes) Landrum (Myrtaceae) has been traditionally used in Brazilian folk medicine. Studies have established the botanical characterization, phytochemistry profile, and pharmacological potential of this species, including antibiotic, anxiolytic, antidepressant, antioxidant, antinociceptive, and anti-inflammatory properties. Despite its widespread use, no previous study has been conducted regarding its toxicological profile, especially during pregnancy. Thus, this study investigated the developmental toxicity of the dry leaf extract of the P. pseudocaryophyllus, (E)-methyl isoeugenol chemotype, in rats. METHODS: First, the dry leaf extract was prepared by a spray-drying technique. Then, pregnant Wistar rats were orally treated with dry extract at doses of 0, 2000, 2500, or 3000 mg/kg from gestational day 6 through 15 (organogenesis period). On gestational day 21, the rats underwent cesarean sections and the reproductive outcomes and biochemistry parameters related to hepatic and renal markers were evaluated. Additionally, the fetuses were examined for external and skeletal variations and malformations. RESULTS: The spray-drying technique preserved the phytocomplex components and showed a satisfactory yield. No relevant differences were seen in the food consumption, reproductive performances, and hepatic and renal biochemical parameters between groups. However, there was a decrease in body weight gain of the dams during the organogenesis period and an increase of minor skeletal variations in the offspring (increased fetal incidences only of delayed ossification of the metacarpals, metatarsals, phalanges, sternebra, and rudimentary ribs) treated with the dry extract. CONCLUSION: The extract of P. pseudocaryophyllus, (E)-methyl isoeugenol chemotype, showed low maternal toxicity and induced minor skeletal variations in the offspring. Birth Defects Research 109:1292-1300, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Anisóis/toxicidade , Pimenta/toxicidade , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Anisóis/metabolismo , Ansiolíticos/farmacologia , Anti-Inflamatórios/farmacologia , Brasil , Feminino , Peso Fetal/efeitos dos fármacos , Feto , Masculino , Medicina Tradicional , Tamanho do Órgão/efeitos dos fármacos , Pimenta/metabolismo , Gravidez , Ratos , Ratos Wistar , Reprodução , Teratogênicos/farmacologia , Aumento de Peso
19.
Cell Physiol Biochem ; 42(1): 81-90, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28528338

RESUMO

BACKGROUND/AIMS: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear. The aim of the present work was to evaluate whether obese adult rats that were chronically treated with an antidiabetic drug, glibenclamide, exhibit resistance to rodent breast carcinoma growth. METHODS: Neonatal rats were treated with monosodium L-glutamate (MSG) to induce prediabetes. Control and MSG groups were treated with Gli (2 mg/kg body weight/day) from weaning to 100 days old. After Gli treatment, the control and MSG rats were grafted with Walker-256 tumour cells. After 14 days, grafted rats were euthanized, and tumour weight as well as glucose homeostasis were evaluated. RESULTS: Treatment with Gli normalized tissue insulin sensitivity and glucose tolerance, suppressed fasting hyperinsulinaemia, reduced fat tissue accretion in MSG rats, and attenuated tumour growth by 27% in control and MSG rats. CONCLUSIONS: Gli treatment also resulted in a large reduction in the number of PCNA-positive tumour cells. Although treatment did improve the metabolism of pre-diabetic MSG-rats, tumour growth inhibition may be a more direct effect of glibenclamide.


Assuntos
Proliferação de Células/efeitos dos fármacos , Glibureto/farmacologia , Estado Pré-Diabético/prevenção & controle , Animais , Caquexia/etiologia , Linhagem Celular Tumoral , Glucose/metabolismo , Glibureto/uso terapêutico , Hiperinsulinismo/prevenção & controle , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Imuno-Histoquímica , Masculino , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Estado Pré-Diabético/etiologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , Glutamato de Sódio/toxicidade
20.
Chemosphere ; 177: 93-101, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28284120

RESUMO

Phytol (PYT) is a diterpenoid having important biological activity. However, it is a water non-soluble compound. This study aims to prepare PYT nanoemulsion (PNE) and evaluation of toxic, cytotoxic and genotoxic activities of PYT and PNE. For this, the PNE was prepared by the phase inversion method. The cytotoxicity test was performed in Artemia salina, while toxicity, cytotoxicity and genotoxicity in Allium cepa at concentrations of 2, 4, 8 and 16 mM. Potassium dichromate and copper sulfate were used as positive controls for the tests of A. salina and A. cepa, respectively. In addition, an adaptation response was detected in A. cepa by using the comet assay. The results suggest that both PYT and PNE exhibited toxic and cytotoxic effects at 4-16 mM in either test system, while genotoxicity at 2-16 mM in A. cepa. PNE exhibited more toxic, cytotoxic and genotoxic effects at 8 and 16 mM than the PYT. However, both PYT and PNE at 2 and 4 mM decreased the index and frequency of damage in A. cepa after 48 and 72 h, suggesting a possible adaptation response or DNA damage preventing capacity. Nanoemulsified PYT (PNE) may readily cross the biological membranes with an increase in bioavailability and produce more toxic, cytotoxic and genotoxic effects in the used test systems.


Assuntos
Artemia/crescimento & desenvolvimento , Dano ao DNA/efeitos dos fármacos , Nanopartículas/toxicidade , Cebolas/citologia , Fitol/toxicidade , Animais , Artemia/efeitos dos fármacos , Ensaio Cometa , Emulsões/química , Emulsões/toxicidade , Nanopartículas/química , Cebolas/efeitos dos fármacos
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