Modelo experimental de administración transdérmica de macromoléculas (tinta china e hidroxitirosol) en cobayas / Transdermal administration of macromolecules (Indian ink and hydroxytyrosol). Experimental model in guinea pigs

Introducción: La administración de sustancias por víatransdérmica, mediante electroporación por pulsos cortosde alto voltaje, ha experimentado un enorme desarrollodurante la última década. Material y métodos: Aplicamossobre la piel de cobayas, 5 ml de las suspensiones de tintachina y de hidroxitirosol al 30% en liposomas, aplicandosimultáneamente ondas electromagnéticas durante veinteminutos. Realizamos el estudio morfológico-ultraestructuraly de análisis de imagen mediante biopsias inmediatas ya las 24 y 96 horas y a los 26 días, así como el estudio cromatográficopor HPLC del hidroxitirosol y sus metabolitosen piel, plasma, músculo e hígado. Resultados: Morfológicamenteobservamos partículas de tinta china en el estratocórneo y en los queratinocitos epidérmicos en las biopsiasinmediatas, mientras que en las posteriores, las observamosademás en los anejos y en la dermis papilar y reticular, sinque se observen alteraciones microscópicas ni ultraestructurales.El estudio cromatográfico puso de manifiesto la presenciade hidroxitirosol en todas las muestras analizadas yde algunos de sus metabolitos en hígado y plasma. Conclusión:La electroporación por ondas hectométricas pulsadasha demostrado el transporte transdérmico de dos sustanciasmacromoleculares (tinta china e hidroxitirosol) en cobayas

Introduction: The transdermal administration of substancesvia high-voltage short-pulse electroporation hasundergone tremendous development over this last decade.Material and Methods: 5 ml of suspension of Indian inkand hydroxytyrosol at 30% in liposomes were applied to theof guinea pigs whilst simultaneously applying electromagneticwaves over a twenty-minute period. A study of themorphological-ultrastructure and image-analysis were performedusing biopsies taken at 0, 24 and 96 hours and alsoat 26 days. A chromatographic study was also carried outvia HPLC of the hydroxytyrosol and its metabolites in skin,plasma, muscle and liver. Results: Morphologically speaking,Indian ink particles were observed in the zero hoursbiopsies at the corneous layer and in epidermal keratinocytes,whilst in subsequent biopsies, said particles were alsoobserved in annexes and in the papillar and reticular dermiswith no observed microscopic or ultrastuctural alterations.The chromatographic study revealed the presence ofhydroxytyrosol in all samples analysed and several of itsmetabolites in liver and plasma. Conclusion: Pulsed-hectometric-wave electroporation has demonstrated the transdermaltransport of two macromolecular substances, Indian inkand hydroxytyrosol, in guinea pigs

Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin.

Melanoma is one of the most frequently metastasizing malignant neoplasias. This study examines an experimental model of pulmonary metastasis and the B16F10 cell subline, highly metastatic in the lung. Antimetastatic effects of the flavonoids tangeretin, rutin, and diosmin were analyzed, and at the same time an analysis of the metastatic activity of ethanol was performed, considered to be necessary because it is used as a vehicle for administering the flavonoids. Lentini's model, which complements the macroscopic evaluation of nodule numbers by using a stereoscopic microscope and image analysis at the microscopic level, was used. The greatest reduction in the number of metastatic nodules (52%) was obtained with diosmin; similarly, the percentages of implantation, growth index, and invasion index (79.40, 67.44, and 45.23%, respectively), were all compared with those of the ethanol group, considered to be an effective control group. Rutin- and tangeretin-treated groups also showed reductions of the same index compared with the ethanol group. It would seem that structural factors would better explain these results and the antimetastatic activity of each flavonoid and the respective metabolites.

[Experimental model for treating pulmonary metastatic melanoma using grape-seed extract, red wine and ethanol]. / Modelo experimental de tratamiento con extracto de semillas de uva, vino tinto y etanol del melanoma metastásico pulmonar.

INTRODUCTION: Melanoma is one of the neoplasias that most frequently metastasize, especially in the lung, where represents a challenge in oncology since current treatment is ineffective, and mortality is high. MATERIAL AND METHODS: Swiss mice (n = 52) were inoculated with 0.5 x 106 B16F10 cell lines and, later, given an oral administration of grape-seed extract, red wine or ethanol. Metastatic nodules on the lung surface were counted and, after processing for microscopy, five sections were selected for image analysis and the invasion index was calculated. RESULTS: Macroscopic analysis showed that grape-seed extract and red wine reduced the number of metastatic nodules by 26.07 and 20.81%, respectively, compared with a control group treated with ethanol. Microscopically, the reduction in the invasion index was 31.65 for grape-seed extract and 17.57% for red wine. CONCLUSION: Ethanol administration significantly increased pulmonary metastasis while grape-seed extract and red wine led to their reduction.

Modelo experimental de tratamiento con extracto de semillas de uva, vino tinto y etanol del melanoma metastásico pulmonar / Experimental model for treating pulmonary metastatic melanoma using grape-seed extract, red wine and ethanol

Introducción. El melanoma es una de las neoplasias malignas que metastatiza con mayor frecuencia, preferentemente en pulmón, representando un reto para la oncología por la ineficacia del tratamiento y la alta tasa de mortalidad. Material y métodos. Inoculamos a 52 ratones Swiss 0,5X106 melanocitos B16F10, a los que administramos oralmente extracto de semilla de uva, vino tinto y etanol. Realizamos el recuento de los nódulos metastásicos de la superficie pulmonar y tras el procesado de los pulmones seleccionamos 5 secciones para su estudio microscópico mediante análisis de imagen, calculando el índice de invasión. Resultados. En el estudio macroscópico el extracto de semillas de uva y el vino tinto originaron una reducción de nódulos metastásicos del 26,07% y del 20,81% respecto al grupo tratado con etanol. Microscópicamente la reducción del índice de invasión fue del 31,65% en el grupo tratado con extracto de semillas de uva y del 17,57% para el del vino. Conclusión. El tratamiento con etanol originó un aumento significativo de las metástasis pulmonares, mientras que el extracto de semillas de uva y el vino tinto las redujeron

Introduction. Melanoma is one of the neoplasias that most frequently metastasize, especially in the lung, where represents a challenge in oncology since current treatment is ineffective, and mortality is high. Material and methods. Swiss mice (n = 52) were inoculated with 0.5 x 106 B16F10 cell lines and, later, given an oral administration of grape-seed extract, red wine or ethanol. Metastatic nodules on the lung surface were counted and, after processing for microscopy, five sections were selected for image analysis and the invasion index was calculated. Results. Macroscopic analysis showed that grape-seed extract and red wine reduced the number of metastatic nodules by 26.07 and 20.81%, respectively, compared with a control group treated with ethanol. Microscopically, the reduction in the invasion index was 31.65 for grape-seed extract and 17.57% for red wine. Conclusion. Ethanol administration significantly increased pulmonary metastasis while grape-seed extract and red wine led to their reduction