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1.
Toxicol Pathol ; 32(1): 73-8, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-14713551

RESUMEN

Prostate-specific antigen (PSA) is a serine protease and one of the most abundant proteins secreted by the human prostate epithelium. PSA is used as a well-established marker of prostate cancer. The involvement of PSA in several early events leading to the development of malignant prostate tumors has made it a target for prevention and intervention. It is thought that PSA cleaves insulin-like growth factor binding protein-3 (IGFBP-3), providing increased local levels of IGF-1, leading to tumor growth. Separately, there are data that suggest an enzymatic regulatory role for dietary boron, which is a serine protease inhibitor. In this study we have addressed the use of boric acid as a PSA inhibitor in an animal study. We have previously reported that low concentrations (6 ug/mL) of boric acid can partially inhibit the proteolytic activity of purified PSA towards a synthetic fluorogenic substrate. Also, by Western blot we have followed the degradation of fibronectin by enzymatically active PSA and have found significant inhibition in the presence of boric acid. We proposed that dietary supplementation with boric acid would inhibit PSA and reduce the development and proliferation of prostate carcinomas in an animal model. We tested this hypothesis using nude mice implanted subcutaneously with LNCaP cells in Matrigel. Two groups (10 animals/group) were dosed with boric acid solutions (1.7, 9.0 mgB/kg/day) by gavage. Control group received only water. Tumor sizes were measured weekly for 8 weeks. Serum PSA and IGF-1 levels were determined at terminal sacrifice. The size of tumors was decreased in mice exposed to the low and high dose of boric acid by 38% and 25%, respectively. Serum PSA levels decreased by 88.6% and 86.4%, respectively, as compared to the control group. There were morphological differences between the tumors in control and boron-dosed animals, including a significantly lower incidence of mitotic figures in the boron-supplemented groups. Circulating IGF-1 levels were not different among groups, though expression of IGF-1 in the tumors was markedly reduced by boron treatment, which we have shown by immunohistochemistry. These data indicate that low-level dietary boron supplementation reduced tumor size and content of a tumor trophic factor, IGF-1. This promising model is being evaluated in further studies.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Ácidos Bóricos/administración & dosificación , Suplementos Dietéticos , Inhibidores Enzimáticos/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Administración Oral , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Antígeno Prostático Específico/antagonistas & inhibidores , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Trasplante Heterólogo , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Biol Trace Elem Res ; 93(1-3): 155-70, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12835499

RESUMEN

Postmenopausal women may benefit from dietary interventions in order to increase bone strength and prevent fractures. Dietary boron (B) may be beneficial for optimal calcium metabolism and, as a consequence, optimal bone metabolism. The present study evaluated the effects of boron, in the form of boric acid, with or without 17beta-estradiol (E2) supplementation (via subcutaneous implant), in ovariectomized (OVX) aged 13- mo-old F-344 rats. Boric acid was administered by gavage at a subtoxic dose (8.7 mg B/kg/d) for 40 d. Results indicate that serum level of minerals as well as osteocalcin (a marker of bone resorption) are dependent to a greater extent on the hormonal status of the animals than on boron supplementation. Boron treatment increased the E2-induced elevation of urinary calcium and magnesium. Bone mineral density (BMD) of the L5 vertebra and proximal femur was highest in the E2-treated groups; no increase in BMD was conferred by boron treatment. By histomorphometry of the proximal tibial metaphysis, osteoblastic, osteoid, and eroded surfaces were significantly suppressed by E2 treatment, but not by boron treatment. In biomechanical testing of femur and vertebra, neither E2 nor boron treatment significantly increased bone strength. At the levels given, boron alone provided no protection against OVX-induced osteopenia. In addition, combination therapy (B + E2) provided no additional benefits over those of 17beta-estradiol treatment alone in this aged rat model.


Asunto(s)
Envejecimiento/fisiología , Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Huesos/metabolismo , Ácidos Bóricos/farmacología , Suplementos Dietéticos , Animales , Fenómenos Biomecánicos , Huesos/fisiología , Ácidos Bóricos/administración & dosificación , Estradiol/farmacología , Femenino , Fémur/efectos de los fármacos , Fémur/metabolismo , Fémur/fisiología , Ovariectomía , Ratas , Ratas Endogámicas F344 , Tibia/efectos de los fármacos , Tibia/metabolismo , Tibia/fisiología , Factores de Tiempo
3.
J Agric Food Chem ; 51(3): 704-9, 2003 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-12537445

RESUMEN

Agricultural crops can be used either to remediate selenium-contaminated soils or to increase the daily selenium intake of consumers after soil supplementation using inorganic or organic selenium sources. In this study, four agricultural crops were examined for potential selenium enhancement. Soils containing tomato, strawberry, radish, and lettuce plants were supplemented with either an inorganic or an organic form of selenium. Two different soils, i.e., low Se and high Se containing, were also used. Statistically significant differences in appearance, fruit production, and fresh weights of the fruit produced were studied. Next, the amount of selenium retained in the edible fruits, nonedible plant, and soil for each was analyzed by acid digestion followed by hydride generation atomic absorption analysis. Finally, inhibition effects on the seeds of the agricultural plants were studied. The results show that supplementation with an inorganic form of selenium led to higher retention in the plants, with a maximum of 97.5% retained in the edible portion of lettuce plants.


Asunto(s)
Agricultura , Lactuca/crecimiento & desarrollo , Raphanus/crecimiento & desarrollo , Selenio/administración & dosificación , Solanum lycopersicum/crecimiento & desarrollo , Fragaria/química , Fragaria/crecimiento & desarrollo , Germinación/efectos de los fármacos , Lactuca/química , Solanum lycopersicum/química , Raphanus/química , Semillas/efectos de los fármacos , Semillas/crecimiento & desarrollo , Selenio/análisis , Suelo/análisis
4.
Prostate ; 54(1): 44-9, 2003 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-12481254

RESUMEN

BACKGROUND: Prostate specific antigen (PSA) is a well-established marker of prostate cancer, but it can also degrade extracellular matrix proteins such as fibronectin and could be involved in tumor progression and metastasis. In this study, we have addressed the use of boric acid and 3-nitrophenyl boronic acid (NPBA) as PSA inhibitors in vitro. METHODS: The inhibition of PSA by boric acid was studied by using specific fluorogenic substrates. Fibronectin, a biologically relevant substrate for PSA, was used as a substrate in a zymographic assay, and the degradation of fibronectin by PSA in the presence of boric acid and NPBA was followed by Western Blot. RESULTS: Low concentrations of boric acid partially inhibited the proteolytic activity of PSA toward a synthetic fluorogenic substrate. Also, by Western blot, we have found significant inhibition in the proteolysis of fibronectin by PSA in the presence of boric acid as well as NPBA. Results indicate that the boronated compounds used in this study can be used for the modulation of PSA activity. CONCLUSION: PSA activity is inhibited in vitro by boric acid and NPBA. If degradation of fibronectin by PSA were, in fact, an important step in the progression of prostate cancer, then borate-induced inhibition of PSA activity should help reduce the development and proliferation of prostate carcinomas.


Asunto(s)
Ácidos Bóricos/farmacología , Ácidos Borónicos/farmacología , Insecticidas/farmacología , Antígeno Prostático Específico/efectos de los fármacos , Antígeno Prostático Específico/farmacología , Neoplasias de la Próstata/fisiopatología , Western Blotting , División Celular , Progresión de la Enfermedad , Inhibidores Enzimáticos/farmacología , Fibronectinas/metabolismo , Humanos , Masculino , Serina Endopeptidasas/farmacología
5.
Artículo en Inglés | MEDLINE | ID: mdl-12369634

RESUMEN

Investigation of lead levels in Delaney Creek, which flows through a former lead-acid battery manufacturing and disposal site in Tampa, FL, revealed low but significant lead levels in the water and sediments along the creek, Known phytoaccumulator plants populate certain locations within the creek and adjacent wetlands. Three representative plants from the study site--cattail (Typha domingensis Pers.), hydrilla (Hydrilla verticillata Royle), and duckweed (Lemna obscura L.)--were investigated for their potential to remove lead from contaminated waters under the controlled conditions of a phytotron room. The plants were collected at the site and cultured in hydroponic medium under conditions that mimicked their natural environment (26 degrees C and 80% humidity). Results indicate that, of the three species, duckweed and hydrilla achieve high lead removal efficiencies after a short exposure period (98% removal using hydrilla, 97% with duckweed after one week of exposure) while cattail appears to be less efficient than the other two species. The kinetic rates of lead removal were studied for Lemna obscura.


Asunto(s)
Araceae/metabolismo , Hydrocharitaceae/metabolismo , Plomo/metabolismo , Typhaceae/metabolismo , Contaminantes Químicos del Agua/metabolismo , Biomasa , Florida , Agua Dulce/química , Cinética , Plomo/aislamiento & purificación , Modelos Biológicos , Espectrofotometría Atómica , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/aislamiento & purificación
6.
Phytochemistry ; 59(3): 305-8, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11830138

RESUMEN

We have been able to isolate several phytotoxic compounds from aqueous extracts and leachates of cattails (Typha domingensis) using activated charcoal as an absorbant, followed by successive extraction with organic solvents, analysis by GC/MS, and structural elucidation by NMR spectroscopy when possible. The phytotoxins were identified as essential fatty acids (linoleic acid and alpha-linolenic acid) and phenolic compounds of known phytotoxic activity (caffeic acid from the aqueous extracts; caffeic, p-coumaric, and gallic acid from the leachates). Both extracts and the phytotoxins in the extracts have the potential of inhibiting the growth and chlorophyll production of several ecologically relevant species.


Asunto(s)
Ácidos Grasos Esenciales/aislamiento & purificación , Hidroxibenzoatos/aislamiento & purificación , Magnoliopsida/química , Extractos Vegetales/química , Ácidos Grasos Esenciales/química , Cromatografía de Gases y Espectrometría de Masas , Hidroxibenzoatos/química , Espectroscopía de Resonancia Magnética , Estructura Molecular
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