Articles

The C60-Fullerene Porphyrin Adducts for Prevention of the Doxorubicin-Induced Acute Cardiotoxicity in Rat Myocardial Cells

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.

Wallace KB, Starkov AA. Mitochondrial targets of drug toxicity. Annu Rev Pharmacol Toxicol 2000;40:353-88.

Souid AK, Tacka KA, Galvan KA, Penefsky HS. Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem Pharmacol 2003;66(6):977-87.

Wallace KB. Doxorubicin-induced cardiac mitochondrionopathy. Pharmacol Toxicol 2003;93(3):105-15.

Tokarska-Schlattner M, Wallimann T, Schlattner U. Multiple interference of anthracyclines with mitochondrial creatine kinases: preferential damage of the cardiac isoenzyme and its implications for drug cardiotoxicity. Mol Pharmacol 2002;61(3):516-23.

Buchachenko AL, Kouznetsov DA, Arkhangelsky SE, Orlova MA, Markarian AA. Spin biochemistry: intramitochondrial nucleotide phosphorylation is a magnesium nuclear spin controlled process. Mitochondrion 2005;5(1):67-9.

Buchachenko AL, Kouznetsov DA, Orlova MA, Markarian AA. Magnetic isotope effect of magnesium in phosphoglycerate kinase phosphorylation. Proc Natl Acad Sci U S A 2005;102(31):10793-6.

Buchachenko AL, Kouznetsov DA, Arkhangelsky SE, Orlova MA, Markarian AA. Spin biochemistry: magnetic 24Mg-25Mg-26Mg isotope effect in mitochondrial ADP phosphorylation. Cell Biochem Biophys 2005;43(2):243-51.

Kouznetsov DA, Arkhangelsky SE, Berdieva AG, Khasigov PZ, Orlova MA. A novel electrophoretic technique designed to modify the ratio of magnesium isotopes inside the creatine kinase active sites. A preliminary report. Isotopes in environmental and health studies 2004;40(3):221-7.

Tishkov VI, Varfolomeyev SD. Editors. [25Mg]-Releasing nanoparticles for the ATP depletion correction in the hypoxia damaged myocardial cells. In: Biocatalysis; 2005, 26 June-1 July; Moscow –St. Petersburg, Russian Federation. Moscow: MSU Press; 2005.

Tyler DD, Gonze J. The preparation of heart mitochondria,from laboratory animals. In: Estabrook RW, Pullman ME, editors. Methods in Enzymology. London: Academic Press Inc; 1967. p. 75-122.

Lowry OH. Protein measurement with the folin phenolmreagent. J Biol Chem 1951;193(1):265-75.

Gouloumis A, Liu SG, Sastre A, Vazquez P, Echegoyen L, Torres T. Synthesis and electrochemical properties of phthalocyanine: fullerene hybrids. Chemistry 2000;6(19):3600-7.

Alonso CMA, Neves MGPMS, Tome AC, Silva AMS, Cavaliero JAS. Synthesis and Diels-Alder reactions of 2- (buta-1,3-dien-2-yl)-5,10,15,20-tetraphenylporphyrin. Tetrahedron Letters 2000;41(30):5679-84.

Hannink RHJ. Nanostructure Control of Materials. UK: CRC Press-Taylor & Francis; 2005.

Sidorov LN, Yurovskaya MA, Borshchevsky AY, Trushkov IV, Ioffe IN. Fullerenes. Russia: Examen Publications; 2005. (in Russian).

Schaefer DM, Reifenberger R, Patil A, Andres RP. Fabrication of two-dimensional arrays of nanometer- size clusters with the atomic force microscope. Appl Phys Lett 1995;66(8):1012-5.

Schmitt L, Ludwig M, Gaub HE, Tampé R. A metalchelating microscopy tip as a new toolbox for singlemolecule experiments by atomic force microscopy. Biophys J 2000;78(6):3275-85.

Fotiadis D, Scheuring S, Müller SA, Engel A, Müller DJ. Imaging and manipulation of biological structures with theAFM. Micron 2002;33(4):385-97.

Abrams GA, Bentley E, Nealey PF, Murphy CJ. Electron microscopy of the canine corneal basement membranes. Cells Tissues Organs 2002;170(4):251-7.

Kuznetsov DA, Govorkov AV, Zavijalov NV, Sibileva TM, Richter V, Drawczek JA. Fast estimation of ATP/ADP ratio as a special step in pharmacological and toxicological studies using the cell-free translation systems. J Biochem Biophys Methods 1986;13(1):53-6.

Vinogradov SA, Wilson DF. Metallotetrabenzoporphyrins. New phosphorescent probes for oxygen measurements. J Chem Soc Perkin Trans II 1995;2(1):103-111.

Lo LW, Koch CJ, Wilson DF. Calibration of oxygendependent quenching of the phosphorescence of Pd-mesotetra (4-carboxyphenyl) porphine: a phosphor with general application for measuring oxygen concentration in biological systems. Anal Biochem 1996;236(1):153-60.

Waugh T, Telashima H. Mitochondria. 1st ed. Raleigh– Durham, NC: Research Triangle Publications; 2004.

Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005;113(7):823-39.

Berdyshev TS, Shtark VL. Lipophilic xenobiotics in the tissue respiration medicinal control. In: Larin SS, Vazhankin OG, editors. Perspectives in experimental pharmaceutical chemistry. 1st edition. Novosibirsk - Tomsk – Moscow: Novosibirsk State University Press; 2004. p. 47-68. (in Russian).

European Patent Application EP1992339. Use of a magnesium isotope for treating hypoxia and a medicament comprising the same. [Online] 2008 Nov 19. Available from: URL:http://www.freepatentsonline.com/EP1992339.html

Malsch NH. Biomedical Nanotechnology. 1st ed. UK: CRC Press - Taylor & Francis Group; 2005.

Ravi Kumar MN. Nano and microparticles as controlled drug delivery devices. J Pharm Pharm Sci 2000;3(2):234-58.

Pankhurst QA, Connolly J, Jones SK, Dobson J. Application of magnetic nanoparticles in biomedicine. J Phys D Appl Phys 2003;36(13):R167-R81. 30. Hughes GA. Nanostructure-mediated drug delivery. Nanomedicine 2005;1(1):22-30.

Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 2002;54(5):631-51.

Freitas RA. What is nanomedicine? Nanomed Nanotechnol Nanotechnol Biol Med 2005; 1(1): 2-10.

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IssueVol 48, No 5 (2010) QRcode
SectionArticles
Keywords
Fullerene nanoparticles doxorubicin-induced cardiotoxicity 25Mg2 mitochondrial dysfunctions.

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How to Cite
1.
Shetab Boushehri SV, Ostad SN, Sarkar S, Kuznetsov DA, Buchachenko AL, Orlova MA, Minaii B, Kebriaeezadeh A, Rezayat SM. The C60-Fullerene Porphyrin Adducts for Prevention of the Doxorubicin-Induced Acute Cardiotoxicity in Rat Myocardial Cells. Acta Med Iran. 1;48(5):342-350.