The C60-fullerene porphyrin adducts for prevention of the doxorubicin-induced acute cardiotoxicity in rat myocardial cells

Acta Med Iran. 2010 Sep-Oct;48(5):342-50.

Abstract

This is a fullerene-based low toxic nanocationite designed for targeted delivery of the paramagnetic stable isotope of magnesium to the doxorubicin (DXR)-induced damaged heart muscle providing a prominent effect close to about 80% recovery of the tissue hypoxia symptoms in less than 24 hrs after a single injection (0.03 - 0.1 LD50). Magnesium magnetic isotope effect selectively stimulates the ATP formation in the oxygen-depleted cells due to a creatine kinase (CK) and mitochondrial respiratory chain-focusing "attack" of 25Mg2+ released by nanoparticles. These "smart nanoparticles" with membranotropic properties release the overactivating cations only in response to the intracellular acidosis. The resulting positive changes in the energy metabolism of heart cell may help to prevent local myocardial hypoxic (ischemic) disorders and, hence, to protect the heart muscle from a serious damage in a vast variety of the hypoxia-induced clinical situations including DXR side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Carboxylic Acids / chemistry*
  • Cell Hypoxia
  • Creatine Kinase / metabolism
  • Cytoprotection
  • Doxorubicin / toxicity*
  • Drug Carriers
  • Energy Metabolism / drug effects
  • Fullerenes / chemistry*
  • Hydrogen-Ion Concentration
  • Lethal Dose 50
  • Magnesium / chemistry
  • Magnesium / pharmacology*
  • Male
  • Metal Nanoparticles
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxygen Consumption / drug effects
  • Porphyrins / chemistry*
  • Rats
  • Rats, Wistar
  • Surface Properties
  • Time Factors

Substances

  • Antibiotics, Antineoplastic
  • C60 carboxyfullerene
  • Carboxylic Acids
  • Drug Carriers
  • Fullerenes
  • Porphyrins
  • Doxorubicin
  • Adenosine Triphosphate
  • Creatine Kinase
  • Magnesium