RESUMEN

OBJECTIVE: Blood-brain barrier is a protective layer that regulates the influx and efflux of biological materials for cerebral tissue. The aim of this study was to investigate the effects of Biochanin A on cerebral histopathology and blood-brain barrier immunohistochemically. METHODS: A total of 24 rats were assigned to three groups: sham, ischemia-reperfusion, and ischemia-reperfusion+Biochanin A. Ischemia-reperfusion was performed by occluding the left carotid artery for 2/24 h. Notably, 20 mg/kg Biochanin A was administered to rats for 7 days after ischemia-reperfusion. Blood was collected for malondialdehyde and total oxidant/antioxidant status analysis. Cerebral tissues were processed for histopathology and further for immunohistochemical analysis. RESULTS: Malondialdehyde content with total oxidant status value was significantly increased and total antioxidant status values were significantly decreased in the ischemia-reperfusion group compared with the sham group. Biochanin A treatment significantly improved scores in the ischemia-reperfusion+Biochanin A group. The normal histological appearance was recorded in the cerebral sections of the sham group. Degenerated neurons and vascular structures with disrupted integrity of the cerebral cortex were observed after ischemia-reperfusion. Biochanin A alleviated the histopathology in the cerebrum in the ischemia-reperfusion+Biochanin A group. Ischemia-reperfusion injury decreased the expression of blood-brain barrier in the ischemia-reperfusion group compared to the sham group. Administration of Biochanin A upregulated the blood-brain barrier immunoreactivity in the cerebrum by restoring blood-brain barrier. CONCLUSION: Cerebral ischemia-reperfusion caused an increase in oxidative stress and pathological lesions in the cerebrum. Biochanin A treatment restored the adverse effects of ischemia-reperfusion injury by restoring blood-brain barrier.

Asunto(s)

Barrera Hematoencefálica , Genisteína , Malondialdehído , Daño por Reperfusión , Animales , Genisteína/farmacología , Genisteína/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Barrera Hematoencefálica/efectos de los fármacos , Masculino , Malondialdehído/análisis , Ratas , Isquemia Encefálica/tratamiento farmacológico , Ratas Wistar , Antioxidantes/farmacología , Inmunohistoquímica , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad

RESUMEN

INTRODUCTION: The third-generation of aromatase inhibitors (AIs)-Exemestane (Exe), Letrozole (Let), and Anastrozole (Ana)-is the main therapeutic approach applied for estrogen receptor-positive (ER+) breast cancer (BC), the most common neoplasm in women worldwide. Despite their success, the development of resistance limits their efficacy. Genistein (G), a phytoestrogen present in soybean, has promising anticancer properties in ER+ BC cells, even when combined with anticancer drugs. Thus, the potential beneficial effects of combining G with AIs were investigated in sensitive (MCF7-aro) and resistant (LTEDaro) BC cells. METHODS: The effects on cell proliferation and expression of aromatase, ERα/ERß, and AR receptors were evaluated. RESULTS: Unlike the combination of G with Ana or Let, which negatively affects the Ais' therapeutic efficacy, G enhanced the anticancer properties of the steroidal AI Exe, increasing the antiproliferative effect and apoptosis relative to Exe. The hormone targets studied were not affected by this combination when compared with Exe. CONCLUSIONS: This is the first in vitro study that highlights the potential benefit of G as an adjuvant therapy with Exe, emphasizing, however, that soy derivatives widely used in the diet or applied as auxiliary medicines may increase the risk of adverse interactions with nonsteroidal AIs used in therapy.

Asunto(s)

Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Genisteína/farmacología , Genisteína/uso terapéutico , Letrozol , Antineoplásicos/uso terapéutico , Nitrilos/uso terapéutico

RESUMEN

OBJECTIVE: The tyrosine-protein kinase inhibitor, genistein, can inhibit cell malignant transformation and has an antitumor effect on various types of cancer. It has been shown that both genistein and KNCK9 can inhibit colon cancer. This research aimed to investigate the suppressive effects of genistein on colon cancer cells and the association between the application of genistein and KCNK9 expression level. METHODS: The Cancer Genome Atlas (TCGA) database was used to study the correlation between the KCNK9 expression level and the prognosis of colon cancer patients. HT29 and SW480 colon cancer cell lines were cultured to examine the inhibitory effects of KCNK9 and genistein on colon cancer in vitro, and a mouse model of colon cancer with liver metastasis was established to verify the inhibitory effect of genistein in vivo. RESULTS: KCNK9 was overexpressed in colon cancer cells and was associated with a shorter Overall Survival (OS), a shorter Disease-Specific Survival (DFS), and a shorter Progression-Free Interval (PFI) of colon cancer patients. In vitro experiments showed that downregulation of KCNK9 or genistein application could suppress cell proliferation, migration, and invasion abilities, induce cell cycle quiescence, promote cell apoptosis, and reduce epithelial-mesenchymal transition of the colon cancer cell line. In vivo experiments revealed that silencing of KCNK9 or application of genistein could inhibit hepatic metastasis from colon cancer. Additionally, genistein could inhibit KCNK9 expression, thereby attenuating Wnt/ß-catenin signaling pathway. CONCLUSION: Genistein inhibited the occurrence and progression of colon cancer through Wnt/ß-catenin signaling pathway that could be mediated by KCNK9.

Asunto(s)

Neoplasias del Colon , Neoplasias Hepáticas , Animales , Ratones , Genisteína/farmacología , Genisteína/uso terapéutico , Proliferación Celular , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Apoptosis , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Vía de Señalización Wnt , Línea Celular Tumoral , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , beta Catenina/genética , beta Catenina/metabolismo , beta Catenina/farmacología

RESUMEN

PURPOSE: To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. METHODS: Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. RESULTS: Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. CONCLUSIONS: Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.

Asunto(s)

Diabetes Mellitus Experimental , Nefropatías Diabéticas , Animales , Glucemia , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/metabolismo , Genisteína/farmacología , Genisteína/uso terapéutico , Riñón , Sistema de Señalización de MAP Quinasas , Mitocondrias , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/farmacología

RESUMEN

Uncontrolled inflammation and failure to resolve the inflammatory response are crucial factors involved in the progress of inflammatory diseases. Current therapeutic strategies aimed at controlling excessive inflammation are effective in some cases, though they may be accompanied by severe side effects, such as immunosuppression. Phytochemicals as a therapeutic alternative can have a fundamental impact on the different stages of inflammation and its resolution. Biochanin A (BCA) is an isoflavone known for its wide range of pharmacological properties, especially its marked anti-inflammatory effects. Recent studies have provided evidence of BCA's abilities to activate events essential for resolving inflammation. In this review, we summarize the most recent findings from pre-clinical studies of the pharmacological effects of BCA on the complex signaling network associated with the onset and resolution of inflammation and BCA's potential protective functionality in several models of inflammatory diseases, such as arthritis, pulmonary disease, neuroinflammation, and metabolic disease.

Asunto(s)

Genisteína , Isoflavonas , Genisteína/farmacología , Genisteína/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Fitoquímicos/farmacología , Fitoterapia

RESUMEN

Paraquat (PQ), an herbicide widely used in agriculture, is considered a highly toxic compound. In hepatocytes, P-glycoprotein (P-gp/Abcb1) is a canalicular transporter involved in PQ extrusion from the cell. Previously, we demonstrated that genistein (GNT) induces P-gp in rat liver. In this study, the protective role of GNT pretreatment towards hepatic damage in a model of acute intoxication with PQ in rats, was investigated. Wistar rats were randomized in 4 groups: Control, GNT (5 mg/kg/day sc, 4 days), PQ (50 mg/kg/day ip, last day) and GNT+ PQ. Hepatic lipoperoxidation (LPO) was evaluated by the thiobarbituric acid reactive substances method. Hepatic levels of 4-hydroxynonenal protein adducts (4-HNEp-add) and glutathione-S-transferase alpha (GSTα) protein expression were evaluated by Western blotting. Hepatic glutathione levels and plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were also measured. Biliary excretion of PQ was studied in vivo and in isolated perfused liver. PQ was quantified by HPLC. PQ significantly increased AST and ALT activities, malondialdehyde and 4-HNEp-add levels, whereby pretreatment with GNT ameliorated this effect. PQ biliary excretion remained unchanged after treatments in both experimental models. Hepatic GSTα expression was augmented in GNT group. GNT pretreatment increased hepatic glutathione levels in PQ + GNT group. These results agree with the lower content of 4-HNEp-adds in GNT + PQ group respect to PQ group. Unexpectedly, increased activity of P-gp did not enhance PQ biliary excretion. Thus, GNT protective mechanism is likely through the induction of GSTα which results in increased 4-HNE metabolism before formation of protein adducts.

Asunto(s)

Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Genisteína/uso terapéutico , Sustancias Protectoras/uso terapéutico , Alanina Transaminasa/sangre , Aldehídos/metabolismo , Animales , Aspartato Aminotransferasas/sangre , Bilis/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Genisteína/farmacología , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Herbicidas , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Paraquat , Sustancias Protectoras/farmacología , Ratas Wistar

RESUMEN

Niemann-Pick type C disease (NPCD) is a lysosomal storage disease (LSD) characterized by abnormal cholesterol accumulation in lysosomes, impaired autophagy flux, and lysosomal dysfunction. The activation of transcription factor EB (TFEB), a master lysosomal function regulator, reduces the accumulation of lysosomal substrates in LSDs where the degradative capacity of the cells is compromised. Genistein can pass the blood-brain barrier and activate TFEB. Hence, we investigated the effect of TFEB activation by genistein toward correcting the NPC phenotype. We show that genistein promotes TFEB translocation to the nucleus in HeLa TFEB-GFP, Huh7, and SHSY-5Y cells treated with U18666A and NPC1 patient fibroblasts. Genistein treatment improved lysosomal protein expression and autophagic flux, decreasing p62 levels and increasing those of the LC3-II in NPC1 patient fibroblasts. Genistein induced an increase in ß-hexosaminidase activity in the culture media of NPC1 patient fibroblasts, suggesting an increase in lysosomal exocytosis, which correlated with a decrease in cholesterol accumulation after filipin staining, including cells treated with U18666A and NPC1 patient fibroblasts. These results support that genistein-mediated TFEB activation corrects pathological phenotypes in NPC models and substantiates the need for further studies on this isoflavonoid as a potential therapeutic agent to treat NPCD and other LSDs with neurological compromise.

Asunto(s)

Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Genisteína/uso terapéutico , Enfermedad de Niemann-Pick Tipo C/tratamiento farmacológico , Enfermedad de Niemann-Pick Tipo C/metabolismo , Androstenos/uso terapéutico , Animales , Western Blotting , Línea Celular Tumoral , Colesterol/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Células HeLa , Humanos , Enfermedades por Almacenamiento Lisosomal , Lisosomas/metabolismo , Proteína Niemann-Pick C1/metabolismo

RESUMEN

OBJECTIVE AND DESIGN: Biochanin A (BCA), a phytoestrogen, has various pharmacological properties. This study was conducted to compare BCA's therapeutic property against 17-ß estradiol replacement therapy in zymosan-induced arthritis (ZIA) in mice. Additionally, we further investigated in vitro the anti-inflammatory action on neutrophils. TREATMENT: Ovariectomized (OVX) and non-OVX mice were pretreated with BCA (1, 3 and 9 mg/kg) or estrogen (50 µg/kg) for 14 days prior to ZIA. Neutrophils were pretreated with BCA (1, 10 and 100 µM) for 1 h prior to phorbol 12-myristate 13-acetate. METHODS: Anti-inflammatory effects of BCA were evaluated by cellular infiltrate, paw edema and cytokine measurement. In vitro, apoptosis was assessed by morphology and flow cytometry. Neutrophil extracellular traps (NET) were determined by fluorescent microscopy and DNA release. Statistical differences were determined by one- or two-way ANOVA. RESULTS: BCA inhibited neutrophil accumulation, paw edema and proinflammatory cytokine (TNF-α and IFN-γ) and increased anti-inflammatory cytokines (IL-4 and IL-10) in OVX and non-OVX mice, similar to 17-ß estradiol replacement therapy. In vitro, BCA increased apoptosis and consequently reduced NETs. CONCLUSION: BCA has a notable anti-inflammatory effect, similar to 17-ß estradiol, and is especially effective for treatment of ZIA. These results suggest that BCA may be promising for the treatment of postmenopausal arthritis.

Asunto(s)

Antiinflamatorios no Esteroideos/uso terapéutico , Artritis/tratamiento farmacológico , Estradiol/uso terapéutico , Terapia de Reemplazo de Estrógeno , Genisteína/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Artritis/inducido químicamente , Citocinas/metabolismo , ADN/metabolismo , Edema/inducido químicamente , Edema/tratamiento farmacológico , Femenino , Ratones , Neutrófilos/efectos de los fármacos , Ovariectomía , Acetato de Tetradecanoilforbol , Zimosan

RESUMEN

La osteoporosis y las enfermedades cardiovasculares son patologías prevalentes en mujeres posmenopáusicas. La calcificación vascular es un proceso en el que se produce una distorsión de la arquitectura natural del tejido arterial con una transformación símil osteogénica. La fisiología vascular y la osteogénesis (formación y remodelación ósea) comparten una complejidad metabólica y funcional crítica, que ha sido poco explorada en forma conjunta, lo que ha impulsado la concepción del Eje Óseo-Vascular como nueva área de investigación, con una visión de estudio integradora con la finalidad de identificar vínculos entre ambos sistemas. En virtud de la controversia planteada sobre los riesgos/beneficios de la terapia de reemplazo hormonal para prevenir enfermedades asociadas a la menopausia, se ha incentivado la búsqueda de nuevas opciones de tratamiento. Los fitoestrógenos, como compuestos nutracéuticos, surgen como una potencial alternativa terapéutica. En particular, las isoflavonas presentan gran analogía estructural con el estrógeno humano 17ß-estradiol, lo que les permite unirse al receptor de estrógenos e inducir acciones estrogénicas tanto en células animales como humanas. Basado en la experiencia propia como en lo reportado en la bibliografía, este artículo analiza la información disponible sobre las acciones vasculares y óseas de los fitoestrógenos (específicamente la isoflavona genisteína), con una visión de ciencia traslacional. Es de esperar que los avances en el conocimiento derivado de la ciencia básica, en un futuro cercano, pueda contribuir a decisiones clínicas a favor de promover terapias naturales de potencial acción dual, para la prevención de enfermedades de alta prevalencia y significativo costo social y económico para la población. (AU)

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Osteoporosis and cardiovascular diseases are prevalent diseases in postmenopausal women. Vascular calcification is a cellmediated process that leads to the loss of the natural architecture of the arterial vessels due to osteogenic transdifferentiation of smooth muscle cells, and matrix mineralization. Vascular physiology and osteogenesis (bone formation and remodeling) share a critical metabolic and functional complexity. Given the emerging integrative nature of the bonevascular axis, links between both systems are a matter of ongoing interest. In view of the controversy stated about the risks/benefits of hormone replacement therapy to prevent diseases associated with menopause, phytoestrogens arise as a potential natural therapeutic alternative. In particular, isoflavones have a strong structural analogy with the human estrogen 17ß-estradiol, that allows them to bind to the estrogen receptor and induce estrogenic actions in animal and human cells. Based in on our own experience and the information available in the literature, in this paper we provide an overview of the role of phytoestrogens on vascular and bone tissues, with focus on Genistein actions. We wish that the basic knowledge acquired may contribute to guide clinical decisions for the promotion of natural therapies for the treatment of diseases that conspire against human health. (AU)

Asunto(s)

Humanos , Masculino , Femenino , Osteogénesis/efectos de los fármacos , Fitoestrógenos/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Calcificación Vascular/tratamiento farmacológico , Osteogénesis/fisiología , Menopausia , Enfermedades Cardiovasculares/complicaciones , Osteoporosis Posmenopáusica , Remodelación Ósea , Genisteína/uso terapéutico , Fitoestrógenos/clasificación , Fitoestrógenos/farmacología , Aterosclerosis/fisiopatología , Estrógenos/biosíntesis , Calcificación Vascular/fisiopatología , Calcificación Vascular/metabolismo

RESUMEN

OBJECTIVES: Low-flow ischemia (LFI) is consequent to coronary disease and produces cardiac stunning during reperfusion (R). Energetic performance and mechanisms of Ca2+ handling during LFI/R are not known. Moreover, cardioprotection of the phytoestrogen genistein (Gen) remains to be demonstrated in LFI/R. The aim was to study the mechanisms of the stunning consequent to LFI/R and the effects of Gen on both sexes. METHODS: Rat ventricles were perfused inside a calorimeter to measure maximal pressure development (P) and total heat rate (Ht) before and during exposition to LFI/R. The mechanisms of stunning were evaluated with selective drugs. KEY FINDINGS: Female hearts (FH) developed higher postischemic contractile recovery (PICR) and muscle economy (P/Ht) than males (MH). Cardioprotection was sensitive to blockade of mKATP channels, UCam and NOS. Perfusion of 20 µmol/l Gen reduced PICR and P/Ht during LFI/R in FH, and dysfunction was increased by mNCX blockade with mPTP opening. However, intraperitoneal 5 mg/kg Gen (Gen-ip) was cardioprotective in both sexes, and the beneficial effect of Gen-ip was blocked by 100 µmol/l 5-HD. CONCLUSIONS: FH are more protected than MH against the LFI/R dysfunction, which involves mitochondrial Ca2+ loss; Gen-ip was more cardioprotective in MH than in FH, mainly by activation of the mKATP channels.

Asunto(s)

Cardiotónicos/uso terapéutico , Metabolismo Energético/fisiología , Genisteína/uso terapéutico , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/prevención & control , Reperfusión Miocárdica/métodos , Animales , Calcio/metabolismo , Cardiotónicos/farmacología , Metabolismo Energético/efectos de los fármacos , Femenino , Genisteína/farmacología , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Ratas , Ratas Sprague-Dawley

RESUMEN

OBJECTIVE AND DESIGN: The present work investigates the modulation of experimental autoimmune encephalomyelitis (EAE) using genistein before the EAE induction. MATERIAL: Female C57BL/6 mice (n = 96 mice/experiment), 4-6 weeks old, were used to induce the EAE. The mice were divided into three experimental groups: non-immunized group, immunized group (EAE), and immunized and treated with genistein group (Genistein). TREATMENT: Genistein was used at a dose of 200 mg/kg s.c. and were initiated 2 days before the immunization and continued daily until day 6 postimmunization. METHODS: Animals were monitored daily for clinical signs of EAE up to day 21. Inflammatory infiltration, demyelination, Toll-like receptor (TLR) expression, cytokines and transcription factors were analyzed in spinal cords. RESULTS: The present study demonstrates, for the first time, the genistein ability to modulate the factors involved in the innate immune response in the early stages of EAE. The genistein therapy delayed the onset of the disease, with reduced inflammatory infiltration and demyelination. In addition, the expression of TLR3, TLR9 and IFN-ß were increased in genistein group, with reduction in the factors of TH1 and Th17 cells. CONCLUSION: These findings shed light on the potential of genistein as a prophylactic strategy for multiple sclerosis (MS) prevention.

Asunto(s)

Encefalomielitis Autoinmune Experimental/inmunología , Genisteína/farmacología , Genisteína/uso terapéutico , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Receptores Toll-Like/inmunología , Animales , Citocinas/genética , Citocinas/inmunología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/prevención & control , Femenino , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones Endogámicos C57BL , Esclerosis Múltiple/prevención & control , Vaina de Mielina/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/inmunología , Médula Espinal/patología

RESUMEN

Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 µg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (∼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.

Asunto(s)

Suplementos Dietéticos , Estrógenos no Esteroides/antagonistas & inhibidores , Genisteína/uso terapéutico , Fenómenos Fisiologicos Nutricionales Maternos , Fitoestrógenos/uso terapéutico , Efectos Tardíos de la Exposición Prenatal/prevención & control , Próstata/efectos de los fármacos , Animales , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/antagonistas & inhibidores , Compuestos de Bencidrilo/toxicidad , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estrógenos no Esteroides/administración & dosificación , Estrógenos no Esteroides/toxicidad , Femenino , Masculino , Fenoles/administración & dosificación , Fenoles/antagonistas & inhibidores , Fenoles/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Próstata/metabolismo , Próstata/patología , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Hiperplasia Prostática/prevención & control , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/prevención & control , Ratas Sprague-Dawley , Receptores Androgénicos/metabolismo , Organismos Libres de Patógenos Específicos , Destete

RESUMEN

PURPOSE: The purpose of this work was the development of a multicompartimental nanocarrier for the simultaneous encapsulation of paclitaxel (PTX) and genistein (GEN), associating antiangiogenic and cytotoxic properties in order to potentiate antitumoral activity. METHOD: Polymeric nanocapsules containing PTX were obtained by interfacial deposition of preformed polymer and coated with a phospholipid bilayer entrapping GEN. Physical-chemical and morphological characteristics were characterized, including size and size distribution, drug entrapment efficiency and drug release profile. In vivo studies were performed in EAT bearing Swiss mice. RESULTS: Entrapment efficiency for both drugs in the nanoparticles was approximately 98%. Average particle diameter was 150 nm with a monomodal distribution. In vitro assays showed distinct temporal drug release profiles for each drug. The dose of 0.2 mg/kg/day of PTX resulted in 11% tumor inhibition, however the association of 12 mg/kg/day of GEN promoted 44% tumor inhibition and a 58% decrease in VEGF levels. CONCLUSIONS: Nanoparticles containing GEN and PTX with a temporal pattern of drug release indicated that the combined effect of cytotoxic and antiangiogenic drugs present in the formulation contributed to the overall enhanced antitumor activity of the nanomedicine.

Asunto(s)

Antineoplásicos/uso terapéutico , Vasos Sanguíneos/metabolismo , Sistemas de Liberación de Medicamentos , Nanopartículas , Neoplasias Experimentales/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Cromatografía Líquida de Alta Presión , Genisteína/administración & dosificación , Genisteína/uso terapéutico , Masculino , Ratones , Microscopía Electrónica de Transmisión , Neoplasias Experimentales/patología , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico

RESUMEN

Fibrosis accompanies most chronic liver disorders and is a major factor contributing to hepatic failure. Therefore, the need for an effective treatment with the aim of modifying the clinical course of this disease is evident. The aim of this work is to determine whether genistein, which has been shown to modulate the physiology and pathophysiology of liver, is able to decrease experimental liver fibrosis and cholestasis. In male Wistar rats, the common bile duct was ligated. Administration of genistein (5 microg rat-1, day-1, p.o.) began four weeks after biliary obstruction and continued for a further four weeks. The liver was used for histological and ultrastructural analysis and for collagen quantification (hydroxyproline content). The degradation of Matrigel(R) and collagen type I was determined in homogenized liver. Bilirubins and enzyme activities were measured in serum. Genistein was able to improve normal liver histology, ultrastructure, collagen content, and biochemical markers of liver damage. It also increased Matrigel(R) and collagen type I degradation. In summary, the present report shows that genistein inhibits the fibrosis and cholestasis induced by prolonged biliary obstruction in the rat. Genistein has therapeutic potential against liver fibrosis.

Asunto(s)

Colestasis Extrahepática/complicaciones , Inhibidores Enzimáticos/uso terapéutico , Genisteína/uso terapéutico , Cirrosis Hepática Experimental/tratamiento farmacológico , Animales , Colestasis Extrahepática/tratamiento farmacológico , Colestasis Extrahepática/patología , Enfermedad Crónica , Estudios de Seguimiento , Hígado/ultraestructura , Cirrosis Hepática Experimental/etiología , Cirrosis Hepática Experimental/patología , Masculino , Microscopía Electrónica , Ratas , Ratas Wistar , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

A soja é um vegetal com altíssimo valor nutritivo e que além de apresentar uma estrutura protéica completa também possui isoflavonas, substâncias com propriedades estrogen-like. Estes componentes presentes na soja produzem efeitos clínicos que são benéficos tanto na prevenção quanto no tratamento de diversas patologias, como o câncer, doenças cardiovasculares, osteoporose e outras, desde que usados regularmente. Para isso há uma variedade de produtos à base de soja, que devem ser utilizados tanto pelo seu valor nutritivo quanto terapêutico

Asunto(s)

Humanos , Anticarcinógenos/farmacocinética , Antineoplásicos/farmacocinética , Diabetes Mellitus/terapia , Enfermedades Cardiovasculares/prevención & control , Glycine max/uso terapéutico , Genisteína/uso terapéutico , Isoflavonas/uso terapéutico , Valor Nutritivo , Osteoporosis/prevención & control , Climaterio , Medicina de Hierbas , Proteínas de Soja