RESUMEN
Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative β-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250 µg/mL) were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed.
Asunto(s)
Animales , Humanos , Masculino , Ratones , Antineoplásicos/farmacología , Chromobacterium/metabolismo , Indoles/farmacología , Neoplasias Experimentales/tratamiento farmacológico , Antineoplásicos/aislamiento & purificación , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Mezclas Complejas , Indoles/aislamiento & purificación , Indoles/uso terapéutico , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative ß-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250â µg/mL) were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed.
Asunto(s)
Antineoplásicos/farmacología , Chromobacterium/metabolismo , Indoles/farmacología , Neoplasias Experimentales/tratamiento farmacológico , Animales , Antineoplásicos/aislamiento & purificación , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Mezclas Complejas , Humanos , Indoles/aislamiento & purificación , Indoles/uso terapéutico , Masculino , Ratones , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
The effect of the administration of a whey protein isolate (WPI) and collagen hydrolysates on ethanol-induced ulcerative lesions was studied in rats. WPI and bovine or porcine collagen hydrolysate (BCH and PCH, respectively) were given to rats by gavage. In acute experiments, (single-dose) physiological saline (10 mL/kg of body weight) was used as the negative control, and carbenoxolone (200 mg/kg of body weight) was used as a positive control. Ethanol (1 mL per 250-g rat) was also given by gavage. These treatments reduced the ulcerative lesion index (ULI) in a range of 40-77%, depending on the dosage. Some mixtures of WPI with either PCH or BCH provided results that suggested synergisms between WPI and the collagen hydrolysates. For example, WPI/BCH (in the proportion of 375:375 mg/kg of body weight) decreased ULI by 64%. The mechanism for mucosal protection involved a decrease in plasma gastrin (approximately 40%), a significant increase (50-267%) in mucus production, and a reduction in ULI (percentage) when intragastric administrations were performed after in vivo alkylation by N-ethylmaleimide. Results suggest that gastrin, sulfhydryl substances, and some mechanisms related to mucus production are all involved in gastric ulcer protection against ethanol. The collagen hydrolysates (both PCH and BCH) presented a stronger effect on mucus production; on the other hand, the effect of WPI was also dependent on sulfhydryl compounds, resulting in a more protective effect when the two proteins were administered together.
Asunto(s)
Antiulcerosos/uso terapéutico , Colágeno/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Proteínas de la Leche/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Estómago/efectos de los fármacos , Alquilación , Animales , Antiulcerosos/farmacología , Carbenoxolona/uso terapéutico , Bovinos , Colágeno/metabolismo , Colágeno/farmacología , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Quimioterapia Combinada , Etanol , Etilmaleimida/metabolismo , Mucosa Gástrica/patología , Gastrinas/sangre , Hidrólisis , Masculino , Proteínas de la Leche/farmacología , Moco/metabolismo , Ratas , Ratas Wistar , Estómago/patología , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Compuestos de Sulfhidrilo/metabolismo , Porcinos , Proteína de Suero de LecheRESUMEN
The protective effect of beef and pig collagen hydrolysates and their fractions were tested as anti-ulcerogenic agents in rats (weighing 250-350 g) against ulcerative lesions caused by ethanol. Beef and pig collagen hydrolysates were fractionated by ultrafiltration into different molecular weight fractions. The protocol employed a negative and a positive control and a single dose of the experimental samples given by intragastric intubation. The beef collagen did not present a dose-response correlation in the ethanol model, whereas pig collagen showed a logarithmic dose-response relationship. Beef collagen hydrolysate decreased the ulcerative lesion index of 55% versus a 61% decrease for pig collagen hydrolysate at the same dosage (750 mg/kg of body weight). No significant differences were found (P > .05) between the hydrolysates and their fractions.