ΑΝΑΛΥΣΗ ΤΩΝ ΑΛΛΗΛΕΠΙΔΡΑΣΕΩΝ ΑΝΘΡΑΚΥΚΛΙΝΩΝ-ΣΙΔΗΡΟΠΟΡΦΥΡΙΝΩΝ ΣΤΟ ΑΙΜΟΠΟΙΗΤΙΚΟ ΣΥΣΤΗΜΑ

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.

Grantor dc:publisher

Aristotle University Of Thessaloniki (AUTH)

Year dc:date

1991

Authors dc:creator

• Παπαδοπούλου, Λευκοθέα
• Papadopoulou, Lefkothea

• 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

Language dc:language

gre

Identifier

10.12681/eadd/1649

OAI identifier oai:identifier

oai:10442/1649