[et_pb_section bb_built=”1″ _builder_version=”3.0.82″ box_shadow_position=”outer”][et_pb_row][et_pb_column type=”4_4″][et_pb_post_title admin_label=”Project Title” _builder_version=”3.0.90″ title=”on” meta=”off” author=”on” date=”on” categories=”on” comments=”on” featured_image=”off” featured_placement=”below” text_color=”dark” text_background=”off” saved_tabs=”all” global_module=”825″ \/][et_pb_toggle _builder_version=”3.0.90″ open=”on” title_text_align=”justify” title=”The Research” icon_color=”#d52f43″ title_font=”|on|||” open_toggle_background_color=”#ffffff” closed_toggle_background_color=”#c5e6f7″ use_border_color=”on” saved_tabs=”all” border_color_all=”#e0d4e9″]<\/p>\n
Iacopo Sardi, *Giancarlo la Marca, *Maria Grazia Giovannini, \u00b0Sabrina Malvagia, \u00b0Renzo Guerrini, \u00b0Lorenzo Genitori, ^Maura Massimino, Maurizio Aric\u00f2<\/p>\n
Department of Onco-Hematology, Meyer Children’s Hospital, Florence Italy
\n*Department of Pharmacology, University of Florence Italy
\n\u00b0Department of Neuroscience, Meyer Children’s Hospital, Florence Italy
\n^Department of Pediatrics, IRCCS Foundation, National Cancer Institute, Milan, Italy<\/p>\n
The blood brain barrier discriminates the access of several molecules into the brain. This hampers the use of some drugs, as doxorubicin, potentially active for treatment of brain tumors. We explored the feasibility of active modification of the blood brain barrier protection, by using morphine pretreatment, to allow doxorubicin accumulation into the brain in an animal model. Rats were pretreated with different doses of intraperitoneal morphine before injection of doxorubicin (12 mg\/kg). Quantitative analysis of doxorubicin was performed by mass spectrometry. Acute hearth and kidney damage was analyzed by measuring doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. The concentration of doxorubicin was significantly higher in all brain areas of rats pretreated with morphine than in control tissues (P <0.001). This was evident only at therapeutic morphine dose (10 mg\/kg, three times over 24 hours), while lower doses (2.5 and 5 mg\/kg) were not associated with doxorubicin accumulation. Pretreatment with morphine did not induce an elevation of LDH activity or of lipid peroxidation compared to controls. Our data suggest that morphine pre-treatment is able to allow doxorubicin penetration inside the brain, by modulating the blood-brain barrier. This is not associated with acute cardiac or renal toxicity. These preliminary results will enable us to generate novel therapeutic approaches to refractory or recurrent brain tumors, and might be useful in other human diseases of the central nervous system in which molecules usually stopped by the blood brain barrier may have a therapeutic impact.<\/p>\n
[\/et_pb_toggle][\/et_pb_column][\/et_pb_row][et_pb_row][et_pb_column type=”4_4″][et_pb_toggle admin_label=”toggle Gli sviluppi” _builder_version=”3.0.90″ open=”off” title_text_align=”justify” title=”Evolution” icon_color=”#d52f43″ title_font=”|on|||” open_toggle_background_color=”#ffffff” closed_toggle_background_color=”#c5e6f7″ use_border_color=”on” saved_tabs=”all” border_color_all=”#e0d4e9″]<\/p>\n
Research project on pediatric brain tumors: Assessment of the cytotoxic effects of the chemotherapeutic drugs used in the treatment of high-risk brain tumors of the pediatric age. L’Ondasetron facilita il passaggio della doxorubicina attraverso la barriera ematoencefalica in modello murino.
“Alteration of the blood-brain barrier (BBB) using drugs that interact with the P-glycoprotein.
New perspectives for the treatment of “poor-responder” brain tumors of the pediatric age”.
Progress Report June 2011.
download pdf (in Italian)<\/a> (112 KB)<\/p>\n
download pdf (in Italian)<\/a> (84 KB)<\/p>\n
download pdf (in Italian)<\/a> (53 KB)<\/p>\n