TRANSMISSION ELECTRON MICROSCOPE STUDY OF THЕAMELIORATING EFFECT OF ARONIA MELANOCARPA ON DOXORUBICIN-INDUCED CARDIOTOXICITY

V. Pavlova1*, B. Alexieva1, I. Sainova1, TZ. Markova2, E. Nikolova1,
S. Kuzmanova3, M. Krachanova4 and P. Denev4
1Institute of Experimental Morphology, Pathology and Anthropology with Museum,
Bulgarian Academy of Sciences, Acad. G. Bonchev str., bl. 25, Sofia 1113, Bulgaria.
2 Department of Pharmacology and Toxicology in MedicalUniversity,
15 Acad. I. Geshovblvd, Sofia 1431, Bulgaria.
3Department of Preclinical and Clinical Pharmacology and Biochemistry,
MedicalUniversity, Varna, Bulgaria.
4Laboratory of Biologically Active Substances, Institute of Organic Chemistry with
Centre of Phytochemistry, Plovdiv, Bulgaria.
Research Article

ABSTRACT

Doxorubicin (DOX) is one of the most effectiveand commonly used antitumor drugswith high
antineoplastic activity to a broad spectrum of cancers.The therapeutic value of DOX, however,
is limited by its dose dependent cardiotoxicity. The free radical-induced cardiac oxidative
stress and reactive oxygen species –caused damage is considered as one of the underlying
mechanisms of DOX-induced cardiotoxicity. Aronia melanocarpa (Black chokeberry) fruits are
rich sources of phenolic substances with one of the most potent antioxidant activities among
plant species. Aronia melanocarpa polyphenols promote the restoration of the main
intracellular antioxidant glutathione (GSH) in the state of oxidative stress, which is crucial for
counteracting the free radical-induced intracellular injury. The aim of our study was to
investigate the possible protective effect of Aronia Melanocarpa fruit juice (AMFJ) against
DOX-induced cardiotoxicity and oxidative stress in an in vivo mouse model. The
administration of DOX (20 mg/kg i. p.) to Balb/c experimental mice caused significant
decrease of tissue glutathione level in heart samples, as well as marked ultrastructural
changes with different degree of damage of cardiomyocytes, examined by electrone
microscope. These biochemical and histological alterations were effectively attenuated on
pretreatment with AMFJ. We concluded that AMFJ had ameliorating effect on DOX-induced
cardiotoxicity and the mechanism of this cytoprotective action is related to the enhancement of
GSH antioxidant pool and reduction of cellular oxidative stress induced by DOX treatment.
Keywords: Antioxidants, Black chokeberry, Cardiotoxicity, Chemotherapy