{"id":{"repo_id":"greece","oai_identifier":"oai:10442/1649"},"canonical_url":"https://search.dev.ndltd.org/etd/greece/oai:10442/1649","repository":{"repo_id":"greece","name":"Greek National Archive of PhD Theses","base_url":"https://phdtheses.ekt.gr/eadd_oai/request"},"display":{"title":"ΑΝΑΛΥΣΗ ΤΩΝ ΑΛΛΗΛΕΠΙΔΡΑΣΕΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ-ΣΙΔΗΡΟΠΟΡΦΥΡΙΝΩΝ ΣΤΟ ΑΙΜΟΠΟΙΗΤΙΚΟ ΣΥΣΤΗΜΑ","abstract":"ADRIAMYCIN (ADR) AND DAUNOMYCIN (DAU) AUNOMYCIN (DAU) ARE TWO OF THE MOST WIDELY AND USED CHEMOTHERAPEUTIC AGENTS FOR TREATMENT OF VARIOUS NEOPLASMS. HOWEVER,THEIR USE IS LIMITED DUE TO THEIR BONE MARROW (MYELOSUPPRESSION) AND CARDIOVASCULAR TOXICITY. UNFORTUNATELY, IT HASN'T BEEN A UNIFIED THEORY TO EXPLAIN THE PLEOTROPIC EFFECTS OF ADR ON SEVERAL TISSUES. THE OBSERVATIONS THAT HEMIN (IRON-PROTOPORPHYRIN IX) COUNTERACTS ADR-INDUCED CYTOTOXICITY SELECTIVELY IN NORMAL AND MALIGNANT HEMOPOIETIC CELLS, LED US TO PROPOSE THAT ADR MAY INTERACT WITH HEMOPROTEINS OF VITAL IMPORTANCE TO BOTH DIVIDING AND NON-DIVINDING CELLS. IN THECONTEXT OF THIS RATIONALE, WE USED [3H(G)]-DAU AND OBSERVED THAT IT INTERACTS SELECTIVELY WITH MITOCHONDRIAL COMPONENTS (OF LARGE M.W.) BY FORMING RELATIVELYSTABLE COMPLEXES. THESE COMPONENTS ARE ENRICHED IN CYTOCHROME C OXIDASE. DETAILED ANALYSIS OF HOW CYTOCHROME C OXIDASE INTERACTS WITH [3H(G)]-DAU INDICATES THAT [3H(G)]-DAU PREFERENTIALLY INTERACTS WITH PEPTIDES CARRYING HEME AS PROSTHETIC GROUPS AND LESS SELECTIVELY WITH CARDIOLIPIN, A PHOSPHOLIPID TIGHTLY ATTACHED TO ENZYME BACKBONE. ADR, LIKE DAU, CAUSES A DOSE- DEPENDENT INHIBITION OF NATURE CYTOCHROME C OXIDASE AT RELATIVELY HIGH CONCENTRATIONS (100-200 MM). THE DEGREE OF ADR-INDUCED INHIBITION OF NATURE CYTOCHROME OXIDASE ACTIVITY SUBSTATIALLY DECREASED BY ADDITION OF EXOGENOUS HEMIN. ALTHOUGH I.P. INJECTION OF HEMIN IN SINGLE-DOSE ADR- TREATED ANIMALS DID NOT FULLY COUNTERACT ADR-INDUCED MYELOSUPPRESSION, IT FACILITATED QUICKER RECOVERY OF BONE MARROW AND CONTRIBUTED TO THE DEVELOPMENT OF STROMAL CELL ENVIRONMENT AND OUTGROWTH OF HEMOPOIETIC AND FIBROBLASTOID COLONIES (CFU-GM, CFU-F) FROM PLATED BONE MARROW CELLS. THEREFORE, THE ABILITY OF HEMIN TO COUNTERACT ANTHRACYCLINES CYTOTOXICITY APPEARS TO BE OF CLINICAL VALUE IN PROTECTING BONE MARROW AND PERHAPS HEART FROM ADR- MYELOSUPPRESSION AND CARDIOTOXICITY, THUS IMPROVING WELL BEING OF PATIENTS UNDERGOING CHEMOTHERAPY TREATMENT.","abstract_html":"ADRIAMYCIN (ADR) AND DAUNOMYCIN (DAU) AUNOMYCIN (DAU) ARE TWO OF THE MOST WIDELY AND USED CHEMOTHERAPEUTIC AGENTS FOR TREATMENT OF VARIOUS NEOPLASMS. HOWEVER,THEIR USE IS LIMITED DUE TO THEIR BONE MARROW (MYELOSUPPRESSION) AND CARDIOVASCULAR TOXICITY. UNFORTUNATELY, IT HASN'T BEEN A UNIFIED THEORY TO EXPLAIN THE PLEOTROPIC EFFECTS OF ADR ON SEVERAL TISSUES. THE OBSERVATIONS THAT HEMIN (IRON-PROTOPORPHYRIN IX) COUNTERACTS ADR-INDUCED CYTOTOXICITY SELECTIVELY IN NORMAL AND MALIGNANT HEMOPOIETIC CELLS, LED US TO PROPOSE THAT ADR MAY INTERACT WITH HEMOPROTEINS OF VITAL IMPORTANCE TO BOTH DIVIDING AND NON-DIVINDING CELLS. IN THECONTEXT OF THIS RATIONALE, WE USED [3H(G)]-DAU AND OBSERVED THAT IT INTERACTS SELECTIVELY WITH MITOCHONDRIAL COMPONENTS (OF LARGE M.W.) BY FORMING RELATIVELYSTABLE COMPLEXES. THESE COMPONENTS ARE ENRICHED IN CYTOCHROME C OXIDASE. DETAILED ANALYSIS OF HOW CYTOCHROME C OXIDASE INTERACTS WITH [3H(G)]-DAU INDICATES THAT [3H(G)]-DAU PREFERENTIALLY INTERACTS WITH PEPTIDES CARRYING HEME AS PROSTHETIC GROUPS AND LESS SELECTIVELY WITH CARDIOLIPIN, A PHOSPHOLIPID TIGHTLY ATTACHED TO ENZYME BACKBONE. ADR, LIKE DAU, CAUSES A DOSE- DEPENDENT INHIBITION OF NATURE CYTOCHROME C OXIDASE AT RELATIVELY HIGH CONCENTRATIONS (100-200 MM). THE DEGREE OF ADR-INDUCED INHIBITION OF NATURE CYTOCHROME OXIDASE ACTIVITY SUBSTATIALLY DECREASED BY ADDITION OF EXOGENOUS HEMIN. ALTHOUGH I.P. INJECTION OF HEMIN IN SINGLE-DOSE ADR- TREATED ANIMALS DID NOT FULLY COUNTERACT ADR-INDUCED MYELOSUPPRESSION, IT FACILITATED QUICKER RECOVERY OF BONE MARROW AND CONTRIBUTED TO THE DEVELOPMENT OF STROMAL CELL ENVIRONMENT AND OUTGROWTH OF HEMOPOIETIC AND FIBROBLASTOID COLONIES (CFU-GM, CFU-F) FROM PLATED BONE MARROW CELLS. THEREFORE, THE ABILITY OF HEMIN TO COUNTERACT ANTHRACYCLINES CYTOTOXICITY APPEARS TO BE OF CLINICAL VALUE IN PROTECTING BONE MARROW AND PERHAPS HEART FROM ADR- MYELOSUPPRESSION AND CARDIOTOXICITY, THUS IMPROVING WELL BEING OF PATIENTS UNDERGOING CHEMOTHERAPY TREATMENT.","abstract_has_math":false,"creators":["Παπαδοπούλου, Λευκοθέα","Papadopoulou, Lefkothea"],"institution":"Aristotle University Of Thessaloniki (AUTH)","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1991,"date_issued":"1991","date_published":"1991","updated_at":"2026-07-24T02:25:02Z","subjects":["Αιμοποίηση","ΑΙΜΟΠΡΩΤΕΙΝΕΣ","Ανθρακυκλίνες","Αντινεοπλασματικά φάρμακα","Μυοκάρδιο","ΠΟΡΦΥΡΙΝΕΣ","AIMINH","Anthracyclines","Antineoplastic agents","Cardiovascular tissue","Hemin","HEMOPOIESIS","HEMOPROTEINS","PROPHYRINS","Ιατρική και Επιστήμες Υγείας","Βασική Ιατρική","Medical and Health Sciences","Basic Medicine"],"languages":["gre"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["10.12681/eadd/1649"],"render_values":[{"text":"10.12681/eadd/1649","href":"https://doi.org/10.12681/eadd/1649","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10442/hedi/1649","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Παπαδοπούλου, Λευκοθέα","Papadopoulou, Lefkothea"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["1991"]},{"key":"dc:publisher","label":"Institution","values":["Aristotle University Of Thessaloniki (AUTH)","Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ)"]},{"key":"dc:type","label":"Dc Type","values":["PhD Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Αιμοποίηση","ΑΙΜΟΠΡΩΤΕΙΝΕΣ","Ανθρακυκλίνες","Αντινεοπλασματικά φάρμακα","Μυοκάρδιο","ΠΟΡΦΥΡΙΝΕΣ","AIMINH","Anthracyclines","Antineoplastic agents","Cardiovascular tissue","Hemin","HEMOPOIESIS","HEMOPROTEINS","PROPHYRINS","Ιατρική και Επιστήμες Υγείας","Βασική Ιατρική","Medical and Health Sciences","Basic Medicine"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["gre"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["10.12681/eadd/1649","http://hdl.handle.net/10442/hedi/1649"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["ADRIAMYCIN (ADR) AND DAUNOMYCIN (DAU) AUNOMYCIN (DAU) ARE TWO OF THE MOST WIDELY AND USED CHEMOTHERAPEUTIC AGENTS FOR TREATMENT OF VARIOUS NEOPLASMS. HOWEVER,THEIR USE IS LIMITED DUE TO THEIR BONE MARROW (MYELOSUPPRESSION) AND CARDIOVASCULAR TOXICITY. UNFORTUNATELY, IT HASN'T BEEN A UNIFIED THEORY TO EXPLAIN THE PLEOTROPIC EFFECTS OF ADR ON SEVERAL TISSUES. THE OBSERVATIONS THAT HEMIN (IRON-PROTOPORPHYRIN IX) COUNTERACTS ADR-INDUCED CYTOTOXICITY SELECTIVELY IN NORMAL AND MALIGNANT HEMOPOIETIC CELLS, LED US TO PROPOSE THAT ADR MAY INTERACT WITH HEMOPROTEINS OF VITAL IMPORTANCE TO BOTH DIVIDING AND NON-DIVINDING CELLS. IN THECONTEXT OF THIS RATIONALE, WE USED [3H(G)]-DAU AND OBSERVED THAT IT INTERACTS SELECTIVELY WITH MITOCHONDRIAL COMPONENTS (OF LARGE M.W.) BY FORMING RELATIVELYSTABLE COMPLEXES. THESE COMPONENTS ARE ENRICHED IN CYTOCHROME C OXIDASE. DETAILED ANALYSIS OF HOW CYTOCHROME C OXIDASE INTERACTS WITH [3H(G)]-DAU INDICATES THAT [3H(G)]-DAU PREFERENTIALLY INTERACTS WITH PEPTIDES CARRYING HEME AS PROSTHETIC GROUPS AND LESS SELECTIVELY WITH CARDIOLIPIN, A PHOSPHOLIPID TIGHTLY ATTACHED TO ENZYME BACKBONE. ADR, LIKE DAU, CAUSES A DOSE- DEPENDENT INHIBITION OF NATURE CYTOCHROME C OXIDASE AT RELATIVELY HIGH CONCENTRATIONS (100-200 MM). THE DEGREE OF ADR-INDUCED INHIBITION OF NATURE CYTOCHROME OXIDASE ACTIVITY SUBSTATIALLY DECREASED BY ADDITION OF EXOGENOUS HEMIN. ALTHOUGH I.P. INJECTION OF HEMIN IN SINGLE-DOSE ADR- TREATED ANIMALS DID NOT FULLY COUNTERACT ADR-INDUCED MYELOSUPPRESSION, IT FACILITATED QUICKER RECOVERY OF BONE MARROW AND CONTRIBUTED TO THE DEVELOPMENT OF STROMAL CELL ENVIRONMENT AND OUTGROWTH OF HEMOPOIETIC AND FIBROBLASTOID COLONIES (CFU-GM, CFU-F) FROM PLATED BONE MARROW CELLS. THEREFORE, THE ABILITY OF HEMIN TO COUNTERACT ANTHRACYCLINES CYTOTOXICITY APPEARS TO BE OF CLINICAL VALUE IN PROTECTING BONE MARROW AND PERHAPS HEART FROM ADR- MYELOSUPPRESSION AND CARDIOTOXICITY, THUS IMPROVING WELL BEING OF PATIENTS UNDERGOING CHEMOTHERAPY TREATMENT.","ΟΙ ΑΝΘΡΑΚΥΚΛΙΝΕΣ ΧΡΗΣΙΜΟΠΟΙΟΥΝΤΑΙ ΕΥΡΕΩΣ ΣΤΗ ΧΗΜΕΙΟΘΕΡΑΠΕΥΤΙΚΗ ΑΓΩΓΗ ΔΙΑΦΟΡΩΝ ΝΕΟΠΛΑΣΜΑΤΩΝ. Η ΧΟΡΗΓΗΣΗ ΤΟΥΣ, ΟΜΩΣ, ΠΕΡΙΟΡΙΖΕΤΑΙ ΛΟΓΩ ΑΝΕΠΙΘΥΜΗΤΩΝ ΕΝΕΡΓΕΙΩΝ ΠΟΥ ΠΡΟΚΑΛΟΥΝ, ΟΙ ΣΗΜΑΝΤΙΚΟΤΕΡΕΣ ΤΩΝ ΟΠΟΙΩΝ ΕΙΝΑΙ Η ΜΥΕΛΟΚΑΤΑΣΤΟΛΗ ΚΑΙ Η ΚΑΡΔΙΟΤΟΞΙΚΟΤΗΤΑ. ΜΕΧΡΙ ΣΤΙΓΜΗΣ ΔΕΝ ΕΙΝΑΙ ΓΝΩΣΤΟΣ ΕΝΑΣ ΕΝΙΑΙΟΣ ΜΗΧΑΝΙΣΜΟΣ, ΜΕΣΩ ΤΟΥ ΟΠΟΙΟΥ ΟΙ ΑΝΘΡΑΚΥΚΛΙΝΕΣ ΑΣΚΟΥΝ ΚΥΤΤΑΡΟΤΟΞΙΚΟΤΗΤΑ ΕΠΙ ΤΟΥ ΑΙΜΟΠΟΙΗΤΙΚΟΥ ΣΥΣΤΗΜΑΤΟΣ ΚΑΙ ΤΟΥ ΜΥΟΚΑΡΔΙΟΥ. ΟΙ ΠΑΡΑΤΗΡΗΣΕΙΣ ΚΑΤΑ ΤΙΣ ΟΠΟΙΕΣ Η ΑΙΜΙΝΗ ΑΝΤΑΓΩΝΙΖΕΤΑΙ ΤΗΝ ΤΟΞΙΚΟΤΗΤΑ ΤΗΣ ADR ΕΠΙ ΛΕΥΧΑΜΙΚΩΝ ΚΑΙ ΦΥΣΙΟΛΟΓΙΚΩΝ ΑΙΜΟΠΟΙΗΤΙΚΩΝ ΚΥΤΤΑΡΩΝ ΣΕ ΚΑΛΛΙΕΡΓΕΙΕΣ ΠΡΟΕΤΡΕΨΑΝ ΝΑ ΔΙΕΥΚΡΙΝΙΣΤΕΙ ΑΝ ΟΙ ΑΝΘΡΑΚΥΚΛΙΝΕΣ (ADR ΚΑΙ DAU) ΑΛΛΗΛΕΠΙΔΡΟΥΝ ΜΕ ΑΙΜΟΠΡΩΤΕΙΝΕΣ ΖΩΤΙΚΗΣ ΣΗΜΑΣΙΑΣ ΤΟΣΟ ΣΕ ΤΑΧΕΩΣ ΠΟΛΛΑΠΛΑΣΙΑΖΟΜΕΝΑ ΚΥΤΤΑΡΑ (ΟΠΩΣ ΤΑ ΑΙΜΟΠΟΙΗΤΙΚΑ) ΟΣΟ ΚΑΙ ΣΕ ΜΗ- ΔΙΑΙΡΟΥΜΕΝΑ ΚΥΤΤΑΡΑ (ΟΠΩΣ ΤΑ ΚΥΤΤΑΡΑ ΤΟΥ ΜΥΟΚΑΡΔΙΟΥ). ΧΡΗΣΙΜΟΠΟΙΩΝΤΑΣ [3Η(G)]- DAU ΔΙΕΥΚΡΙΝΙΣΤΗΚΕ ΟΤΙ Η DAU ΑΝΤΙΔΡΑ ΕΚΛΕΚΤΙΚΑ ΜΕ ΜΕΓΑΛΟΥ ΜΒ ΜΙΤΟΧΟΝΔΡΙΑΚΑ ΠΡΩΤΕΙΝΙΚΑ ΚΛΑΣΜΑΤΑ ΕΜΠΛΟΥΤΙΣΜΕΝΑ ΣΕ ΟΞΕΙΔΑΣΗ ΤΟΥ ΚΥΤΟΧΡΩΜΑΤΟΣ C. Η ΑΝΤΙΔΡΑΣΗ ΑΥΤΗ ΠΡΕΠΕΙ ΝΑ ΕΠΙΤΕΛΕΙΤΑΙ ΜΕΣΩ ΔΥΟ ΤΟΥΛΑΧΙΣΤΟΝ ΘΕΣΕΩΝ ΣΥΝΔΕΣΗΣ, ΕΚ ΤΩΝ ΟΠΟΙΩΝ Η ΣΗΜΑΝΤΙΚΟΤΕΡΗ ΦΑΙΝΕΤΑΙ ΝΑ ΑΠΟΤΕΛΕΙΤΑΙ ΑΠΟ ΤΗΝ ΠΡΟΣΘΕΤΙΚΗ ΟΜΑΔΑ ΤΗΣ ΑΙΜΗΣ ΚΑΙ Η ΑΛΛΗ ΑΠΟ ΤΟ ΦΩΣΦΟΛΙΠΟΕΙΔΕΣ ΚΑΡΔΙΟΛΙΠΙΝΗ.ΤΟΣΟ Η ADR ΟΣΟ ΚΑΙ Η DAU ΑΝΑΣΤΕΛΛΟΥΝ, ΣΕ ΥΨΗΛΕΣ ΣΥΓΚΕΝΤΡΩΣΕΙΣ (100-200 ΜΜ), ΤΗΔΡΑΣΤΙΚΟΤΗΤΑ ΤΟΥ ΕΝΖΥΜΟΥ \"ΟΞΕΙΔΑΣΗ ΤΟΥ ΚΥΤΟΧΡΩΜΑΤΟΣ C\". ΠΑΡΟΥΣΙΑ ΤΗΣ ΑΙΜΙΝΗΣ ΗΑΝΑΣΤΟΛΗ ΑΥΤΗ ΠΕΡΙΟΡΙΖΕΤΑΙ ΚΑΤΑ 30%-50%. ΕΠΙΠΛΕΟΝ, Η ΑΙΜΙΝΗ ΠΕΡΙΟΡΙΖΕΙ ΤΟ ΒΑΘΜΟ ΤΗΣ ΠΡΟΚΑΛΟΥΜΕΝΗΣ ΑΠΟ ΤΗΝ ADR ΜΥΕΛΟΚΑΤΑΣΤΟΛΗΣ IN VIVO ΣΕ ΠΕΙΡΑΜΑΤΟΖΩΑ, ΕΠΙΤΡΕΠΟΝΤΑΣ ΕΤΣΙ ΤΑΧΥΤΕΡΗ ΑΝΑΛΗΨΗ ΤΟΥ ΜΥΕΛΟΥ ΤΩΝ ΟΣΤΩΝ ΚΑΙ ΔΙΑΤΗΡΗΣΗ ΤΗΣ ΑΝΑΠΑΡΑΓΩΓΙΚΗΣ ΙΚΑΝΟΤΗΤΑΣ ΤΩΝ ΠΡΟΔΡΟΜΩΝ ΚΥΤΤΑΡΩΝ ΤΟΥ ΜΥΕΛΟΥ (ΑΙΜΟΠΟΙΗΤΙΚΩΝ ΚΑΙ ΙΝΟΒΛΑΣΤΟΕΙΔΩΝ) ΝΑ ΣΧΗΜΑΤΙΣΟΥΝ ΑΝΤΙΣΤΟΙΧΑ ΑΠΟΙΚΙΕΣ (CFU-GM, CFU-F) ΚΑΙ \"ΣΤΡΩΜΑ\" ΣΕ ΚΑΛΛΙΕΡΓΕΙΕΣ. Η ΙΚΑΝΟΤΗΤΑ ΑΥΤΗ ΤΗΣ ΑΙΜΙΝΗΣ ΝΑ ΑΝΤΑΓΩΝΙΖΕΤΑΙ ΤΗΝ ΚΥΤΤΑΡΟΤΟΞΙΚΟΤΗΤΑ ΤΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ ΣΤΟ ΕΠΙΠΕΔΟ ΤΟΥ ΜΥΕΛΟΥ ΤΩΝ ΟΣΤΩΝ ΚΑΙ ΠΙΘΑΝΟΝ ΚΑΙ ΤΟΥ ΜΥΟΚΑΡΔΙΟΥ ΘΑ ΜΠΟΡΟΥΣΕ ΝΑ ΤΥΧΕΙ ΚΛΙΝΙΚΗΣ ΕΦΑΡΜΟΓΗΣ ΣΤΟΝ ΕΛΕΓΧΟ ΤΗΣ ΜΥΕΛΟΚΑΤΑΣΤΟΛΗΣ ΚΑΙ ΤΗΣ ΚΑΡΔΙΟΤΟΞΙΚΟΤΗΤΑΣ ΤΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ ΚΑΤΑ ΤΗ ΘΕΡΑΠΕΥΤΙΚΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΜΗ-ΑΙΜΟΠΟΙΗΤΙΚΩΝ ΝΕΟΠΛΑΣΜΑΤΩΝ."]},{"key":"dc:title","label":"Title","values":["ΑΝΑΛΥΣΗ ΤΩΝ ΑΛΛΗΛΕΠΙΔΡΑΣΕΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ-ΣΙΔΗΡΟΠΟΡΦΥΡΙΝΩΝ ΣΤΟ ΑΙΜΟΠΟΙΗΤΙΚΟ ΣΥΣΤΗΜΑ","INTERACTIONS BETWEEN ANTHRACYCLINES AND IRON-PROPHYRINS IN HEMOPOIETIC SYSTEM"]}]}],"canonical_facts":{"dc:creator":["Παπαδοπούλου, Λευκοθέα","Papadopoulou, Lefkothea"],"dc:date":["1991"],"dc:description":["ADRIAMYCIN (ADR) AND DAUNOMYCIN (DAU) AUNOMYCIN (DAU) ARE TWO OF THE MOST WIDELY AND USED CHEMOTHERAPEUTIC AGENTS FOR TREATMENT OF VARIOUS NEOPLASMS. HOWEVER,THEIR USE IS LIMITED DUE TO THEIR BONE MARROW (MYELOSUPPRESSION) AND CARDIOVASCULAR TOXICITY. UNFORTUNATELY, IT HASN'T BEEN A UNIFIED THEORY TO EXPLAIN THE PLEOTROPIC EFFECTS OF ADR ON SEVERAL TISSUES. THE OBSERVATIONS THAT HEMIN (IRON-PROTOPORPHYRIN IX) COUNTERACTS ADR-INDUCED CYTOTOXICITY SELECTIVELY IN NORMAL AND MALIGNANT HEMOPOIETIC CELLS, LED US TO PROPOSE THAT ADR MAY INTERACT WITH HEMOPROTEINS OF VITAL IMPORTANCE TO BOTH DIVIDING AND NON-DIVINDING CELLS. IN THECONTEXT OF THIS RATIONALE, WE USED [3H(G)]-DAU AND OBSERVED THAT IT INTERACTS SELECTIVELY WITH MITOCHONDRIAL COMPONENTS (OF LARGE M.W.) BY FORMING RELATIVELYSTABLE COMPLEXES. THESE COMPONENTS ARE ENRICHED IN CYTOCHROME C OXIDASE. DETAILED ANALYSIS OF HOW CYTOCHROME C OXIDASE INTERACTS WITH [3H(G)]-DAU INDICATES THAT [3H(G)]-DAU PREFERENTIALLY INTERACTS WITH PEPTIDES CARRYING HEME AS PROSTHETIC GROUPS AND LESS SELECTIVELY WITH CARDIOLIPIN, A PHOSPHOLIPID TIGHTLY ATTACHED TO ENZYME BACKBONE. ADR, LIKE DAU, CAUSES A DOSE- DEPENDENT INHIBITION OF NATURE CYTOCHROME C OXIDASE AT RELATIVELY HIGH CONCENTRATIONS (100-200 MM). THE DEGREE OF ADR-INDUCED INHIBITION OF NATURE CYTOCHROME OXIDASE ACTIVITY SUBSTATIALLY DECREASED BY ADDITION OF EXOGENOUS HEMIN. ALTHOUGH I.P. INJECTION OF HEMIN IN SINGLE-DOSE ADR- TREATED ANIMALS DID NOT FULLY COUNTERACT ADR-INDUCED MYELOSUPPRESSION, IT FACILITATED QUICKER RECOVERY OF BONE MARROW AND CONTRIBUTED TO THE DEVELOPMENT OF STROMAL CELL ENVIRONMENT AND OUTGROWTH OF HEMOPOIETIC AND FIBROBLASTOID COLONIES (CFU-GM, CFU-F) FROM PLATED BONE MARROW CELLS. THEREFORE, THE ABILITY OF HEMIN TO COUNTERACT ANTHRACYCLINES CYTOTOXICITY APPEARS TO BE OF CLINICAL VALUE IN PROTECTING BONE MARROW AND PERHAPS HEART FROM ADR- MYELOSUPPRESSION AND CARDIOTOXICITY, THUS IMPROVING WELL BEING OF PATIENTS UNDERGOING CHEMOTHERAPY TREATMENT.","ΟΙ ΑΝΘΡΑΚΥΚΛΙΝΕΣ ΧΡΗΣΙΜΟΠΟΙΟΥΝΤΑΙ ΕΥΡΕΩΣ ΣΤΗ ΧΗΜΕΙΟΘΕΡΑΠΕΥΤΙΚΗ ΑΓΩΓΗ ΔΙΑΦΟΡΩΝ ΝΕΟΠΛΑΣΜΑΤΩΝ. Η ΧΟΡΗΓΗΣΗ ΤΟΥΣ, ΟΜΩΣ, ΠΕΡΙΟΡΙΖΕΤΑΙ ΛΟΓΩ ΑΝΕΠΙΘΥΜΗΤΩΝ ΕΝΕΡΓΕΙΩΝ ΠΟΥ ΠΡΟΚΑΛΟΥΝ, ΟΙ ΣΗΜΑΝΤΙΚΟΤΕΡΕΣ ΤΩΝ ΟΠΟΙΩΝ ΕΙΝΑΙ Η ΜΥΕΛΟΚΑΤΑΣΤΟΛΗ ΚΑΙ Η ΚΑΡΔΙΟΤΟΞΙΚΟΤΗΤΑ. ΜΕΧΡΙ ΣΤΙΓΜΗΣ ΔΕΝ ΕΙΝΑΙ ΓΝΩΣΤΟΣ ΕΝΑΣ ΕΝΙΑΙΟΣ ΜΗΧΑΝΙΣΜΟΣ, ΜΕΣΩ ΤΟΥ ΟΠΟΙΟΥ ΟΙ ΑΝΘΡΑΚΥΚΛΙΝΕΣ ΑΣΚΟΥΝ ΚΥΤΤΑΡΟΤΟΞΙΚΟΤΗΤΑ ΕΠΙ ΤΟΥ ΑΙΜΟΠΟΙΗΤΙΚΟΥ ΣΥΣΤΗΜΑΤΟΣ ΚΑΙ ΤΟΥ ΜΥΟΚΑΡΔΙΟΥ. ΟΙ ΠΑΡΑΤΗΡΗΣΕΙΣ ΚΑΤΑ ΤΙΣ ΟΠΟΙΕΣ Η ΑΙΜΙΝΗ ΑΝΤΑΓΩΝΙΖΕΤΑΙ ΤΗΝ ΤΟΞΙΚΟΤΗΤΑ ΤΗΣ ADR ΕΠΙ ΛΕΥΧΑΜΙΚΩΝ ΚΑΙ ΦΥΣΙΟΛΟΓΙΚΩΝ ΑΙΜΟΠΟΙΗΤΙΚΩΝ ΚΥΤΤΑΡΩΝ ΣΕ ΚΑΛΛΙΕΡΓΕΙΕΣ ΠΡΟΕΤΡΕΨΑΝ ΝΑ ΔΙΕΥΚΡΙΝΙΣΤΕΙ ΑΝ ΟΙ ΑΝΘΡΑΚΥΚΛΙΝΕΣ (ADR ΚΑΙ DAU) ΑΛΛΗΛΕΠΙΔΡΟΥΝ ΜΕ ΑΙΜΟΠΡΩΤΕΙΝΕΣ ΖΩΤΙΚΗΣ ΣΗΜΑΣΙΑΣ ΤΟΣΟ ΣΕ ΤΑΧΕΩΣ ΠΟΛΛΑΠΛΑΣΙΑΖΟΜΕΝΑ ΚΥΤΤΑΡΑ (ΟΠΩΣ ΤΑ ΑΙΜΟΠΟΙΗΤΙΚΑ) ΟΣΟ ΚΑΙ ΣΕ ΜΗ- ΔΙΑΙΡΟΥΜΕΝΑ ΚΥΤΤΑΡΑ (ΟΠΩΣ ΤΑ ΚΥΤΤΑΡΑ ΤΟΥ ΜΥΟΚΑΡΔΙΟΥ). ΧΡΗΣΙΜΟΠΟΙΩΝΤΑΣ [3Η(G)]- DAU ΔΙΕΥΚΡΙΝΙΣΤΗΚΕ ΟΤΙ Η DAU ΑΝΤΙΔΡΑ ΕΚΛΕΚΤΙΚΑ ΜΕ ΜΕΓΑΛΟΥ ΜΒ ΜΙΤΟΧΟΝΔΡΙΑΚΑ ΠΡΩΤΕΙΝΙΚΑ ΚΛΑΣΜΑΤΑ ΕΜΠΛΟΥΤΙΣΜΕΝΑ ΣΕ ΟΞΕΙΔΑΣΗ ΤΟΥ ΚΥΤΟΧΡΩΜΑΤΟΣ C. Η ΑΝΤΙΔΡΑΣΗ ΑΥΤΗ ΠΡΕΠΕΙ ΝΑ ΕΠΙΤΕΛΕΙΤΑΙ ΜΕΣΩ ΔΥΟ ΤΟΥΛΑΧΙΣΤΟΝ ΘΕΣΕΩΝ ΣΥΝΔΕΣΗΣ, ΕΚ ΤΩΝ ΟΠΟΙΩΝ Η ΣΗΜΑΝΤΙΚΟΤΕΡΗ ΦΑΙΝΕΤΑΙ ΝΑ ΑΠΟΤΕΛΕΙΤΑΙ ΑΠΟ ΤΗΝ ΠΡΟΣΘΕΤΙΚΗ ΟΜΑΔΑ ΤΗΣ ΑΙΜΗΣ ΚΑΙ Η ΑΛΛΗ ΑΠΟ ΤΟ ΦΩΣΦΟΛΙΠΟΕΙΔΕΣ ΚΑΡΔΙΟΛΙΠΙΝΗ.ΤΟΣΟ Η ADR ΟΣΟ ΚΑΙ Η DAU ΑΝΑΣΤΕΛΛΟΥΝ, ΣΕ ΥΨΗΛΕΣ ΣΥΓΚΕΝΤΡΩΣΕΙΣ (100-200 ΜΜ), ΤΗΔΡΑΣΤΙΚΟΤΗΤΑ ΤΟΥ ΕΝΖΥΜΟΥ \"ΟΞΕΙΔΑΣΗ ΤΟΥ ΚΥΤΟΧΡΩΜΑΤΟΣ C\". ΠΑΡΟΥΣΙΑ ΤΗΣ ΑΙΜΙΝΗΣ ΗΑΝΑΣΤΟΛΗ ΑΥΤΗ ΠΕΡΙΟΡΙΖΕΤΑΙ ΚΑΤΑ 30%-50%. ΕΠΙΠΛΕΟΝ, Η ΑΙΜΙΝΗ ΠΕΡΙΟΡΙΖΕΙ ΤΟ ΒΑΘΜΟ ΤΗΣ ΠΡΟΚΑΛΟΥΜΕΝΗΣ ΑΠΟ ΤΗΝ ADR ΜΥΕΛΟΚΑΤΑΣΤΟΛΗΣ IN VIVO ΣΕ ΠΕΙΡΑΜΑΤΟΖΩΑ, ΕΠΙΤΡΕΠΟΝΤΑΣ ΕΤΣΙ ΤΑΧΥΤΕΡΗ ΑΝΑΛΗΨΗ ΤΟΥ ΜΥΕΛΟΥ ΤΩΝ ΟΣΤΩΝ ΚΑΙ ΔΙΑΤΗΡΗΣΗ ΤΗΣ ΑΝΑΠΑΡΑΓΩΓΙΚΗΣ ΙΚΑΝΟΤΗΤΑΣ ΤΩΝ ΠΡΟΔΡΟΜΩΝ ΚΥΤΤΑΡΩΝ ΤΟΥ ΜΥΕΛΟΥ (ΑΙΜΟΠΟΙΗΤΙΚΩΝ ΚΑΙ ΙΝΟΒΛΑΣΤΟΕΙΔΩΝ) ΝΑ ΣΧΗΜΑΤΙΣΟΥΝ ΑΝΤΙΣΤΟΙΧΑ ΑΠΟΙΚΙΕΣ (CFU-GM, CFU-F) ΚΑΙ \"ΣΤΡΩΜΑ\" ΣΕ ΚΑΛΛΙΕΡΓΕΙΕΣ. Η ΙΚΑΝΟΤΗΤΑ ΑΥΤΗ ΤΗΣ ΑΙΜΙΝΗΣ ΝΑ ΑΝΤΑΓΩΝΙΖΕΤΑΙ ΤΗΝ ΚΥΤΤΑΡΟΤΟΞΙΚΟΤΗΤΑ ΤΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ ΣΤΟ ΕΠΙΠΕΔΟ ΤΟΥ ΜΥΕΛΟΥ ΤΩΝ ΟΣΤΩΝ ΚΑΙ ΠΙΘΑΝΟΝ ΚΑΙ ΤΟΥ ΜΥΟΚΑΡΔΙΟΥ ΘΑ ΜΠΟΡΟΥΣΕ ΝΑ ΤΥΧΕΙ ΚΛΙΝΙΚΗΣ ΕΦΑΡΜΟΓΗΣ ΣΤΟΝ ΕΛΕΓΧΟ ΤΗΣ ΜΥΕΛΟΚΑΤΑΣΤΟΛΗΣ ΚΑΙ ΤΗΣ ΚΑΡΔΙΟΤΟΞΙΚΟΤΗΤΑΣ ΤΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ ΚΑΤΑ ΤΗ ΘΕΡΑΠΕΥΤΙΚΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΜΗ-ΑΙΜΟΠΟΙΗΤΙΚΩΝ ΝΕΟΠΛΑΣΜΑΤΩΝ."],"dc:identifier":["10.12681/eadd/1649","http://hdl.handle.net/10442/hedi/1649"],"dc:language":["gre"],"dc:publisher":["Aristotle University Of Thessaloniki (AUTH)","Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης (ΑΠΘ)"],"dc:subject":["Αιμοποίηση","ΑΙΜΟΠΡΩΤΕΙΝΕΣ","Ανθρακυκλίνες","Αντινεοπλασματικά φάρμακα","Μυοκάρδιο","ΠΟΡΦΥΡΙΝΕΣ","AIMINH","Anthracyclines","Antineoplastic agents","Cardiovascular tissue","Hemin","HEMOPOIESIS","HEMOPROTEINS","PROPHYRINS","Ιατρική και Επιστήμες Υγείας","Βασική Ιατρική","Medical and Health Sciences","Basic Medicine"],"dc:title":["ΑΝΑΛΥΣΗ ΤΩΝ ΑΛΛΗΛΕΠΙΔΡΑΣΕΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ-ΣΙΔΗΡΟΠΟΡΦΥΡΙΝΩΝ ΣΤΟ ΑΙΜΟΠΟΙΗΤΙΚΟ ΣΥΣΤΗΜΑ","INTERACTIONS BETWEEN ANTHRACYCLINES AND IRON-PROPHYRINS IN HEMOPOIETIC SYSTEM"],"dc:type":["PhD Thesis"]},"updated_at":"2026-07-24T02:25:02Z"}