RESUMEN
The 21-aminosteroids (or lazaroids) are a recently synthesized class of compounds demonstrated to protect tissue against damage induced by trauma and/or ischemia. Currently, very little is known about the biological effects of lazaroids. In this work the action of lazaroid U-75412E on a human epithelial cell line (Wish) was evaluated. The data obtained showed an inhibition of cell growth and a dose- and time-dependent decrease of cell viability. Furthermore, a dose- and time-dependent increase of cells in the G2/M phase with the appearance of apoptotic cells was observed by flow cytometric analysis. Nuclear fragmentation was also evident. Lactate dehydrogenase release and scanning electron microscopy experiments suggested that plasma membrane integrity was altered by this compound. The immunofluorescence technique and transmission electron microscopy images also showed intracellular damage, such as alteration of microtubular arrangement, mitochondrial swelling and the presence of vacuoles. This study demonstrated that 1 microM U-75412E was unable to modify these parameters, while higher concentrations (6-75 microM) had a cytotoxic effect on Wish cells.
Asunto(s)
Antioxidantes/toxicidad , Esteroides/toxicidad , Apoptosis , División Celular/efectos de los fármacos , Línea Celular/efectos de los fármacos , Línea Celular/ultraestructura , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Epitelio/efectos de los fármacos , Humanos , L-Lactato Deshidrogenasa/análisis , Factores de TiempoRESUMEN
The in vitro sensitivity of nine Trichomonas vaginalis isolates to commonly employed 5-nitroimidazoles (metronidazole, nimorazole, ornidazole and tinidazole) was evaluated in absence and in presence of sub-inhibitory concentrations of hydrogen peroxide (H2O2). Co-incubation with H2O2 and 5-nitroimidazole compounds decreased the MIC values of the strains exhibiting cross-resistance to these drugs. It was suggested that H2O2 produced in the inflammatory process during trichomonal infection could enhance the therapeutic effect of 5-nitroimidazole drugs.
Asunto(s)
Antitricomonas/farmacología , Peróxido de Hidrógeno/farmacología , Nitroimidazoles/farmacología , Trichomonas vaginalis/efectos de los fármacos , Animales , Interacciones Farmacológicas , Pruebas de Sensibilidad MicrobianaRESUMEN
The effect of hydrogen peroxide on cultured epithelial cells (WISH) was investigated with particular emphasis on cell functions: cell morphology and cytoskeletal components were also studied. The presence of low concentrations of H(2)O(2) (0.1-0.4 mM) in the culture medium markedly inhibited cell growth, although WISH contained catalase and glutathione-peroxidase activities. After 1 hr of incubation with H(2)O(2) up to 5 mM, the majority of the cells were still alive, but reincubation in normal medium for 24 hr clearly reduced cell viability. Cell adhesion was dose-dependently reduced by H(2)O(2) treatment (0.1-0.5 mM) for 4 hr. Incubation with 1.5 mM-H(2)O(2) gave rise to a bleb appearance on the cell surface and to mitochondrial swelling, as shown, respectively, by scanning and transmission electron microscopy. Immunofluorescence studies revealed changes in microtubules and microfilaments, which are two of the main cytoskeletal components. The modification of microtubules was also confirmed by Western blot analysis of WISH protein homogenates submitted to SDS-PAGE. WISH treated with 1.5 mM-H(2)O(2) showed decreased levels of GSH compared with control cells: glutathione transferase activity was reduced, whereas other enzymes of the glutathione cycle were unchanged.
RESUMEN
For a better study of the great number of species constituting the medicinal plants of the Mediterranean area, ethnobotanical maps are actually being produced by the Italian Botanical Society. The following points are raised: (1) the study of the ancient books of Materia Medica of the various countries which preserve, better than anywhere else, the true traditions; these have, in part, been passed on to the modern pharmacopoeias; (2) the importance of the determination of the species of medicinal plants; (3) the different uses of a plant in different countries; (4) the importance of taxonomy and chemotaxonomy for more precise studies of the species containing active principles. Conservation of species must be one of the primary objectives at present, and therefore the formation of "germ plasma" banks for the main medicinal plants in order to preserve their genetical patrimonies is suggested.