Search Results

1 - 10 of 57 items :

  • "Adriamycin" x
Clear All

Abstract

Adriamycin (doxorubicin) is a chemical substance in the anthracycline class with a wide range of applications in oncology and hematology. The mechanism of action of Adriamycin is related to formation of irregular bonds between nucleobases of DNA and inhibition of key enzymes of DNA synthesis - topoisomerase I and II as well as to formation of free radicals damaging DNA.

A major limitation in the drug use is associated with its adverse effects such as cardiotoxicity and hepatotoxicity.

The mechanism of myocardial injury by Adriamycin is linked to an increase in oxidative stress associated with impaired mitochondrial function and structure.

Cardiotoxicity of anthracyclines is classified as: acute, chronic or late (delayed).

Hepatotoxicity of Adriamycin as a damage of the liver is associated with a dysfunction of this organ. Adriamycin studies have shown increased level of transaminase present in 40% of patients treated with Adriamycin. The state was transient and asymptomatic, returning to the initial level even when treatment continued.

Knowledge of cancer diseases contributed to a successive creation of two improved forms of Adriamycin (doxorubicin) – nonpegylated and pegylated formulas of the drug.

The mechanism of anticancer effects of liposomal Adriamycin is similar to the mechanism of conventional Adriamycin, but placement of the molecules of active substance in liposomes has significant influence on the distribution of the drug.

In order to increase the distribution of the drug, a special form of liposomal Adriamycin has been created by covering the surface of the liposomes with a hydrophilic polymer - (MPEG). This process, known as pegylation, decreases the interactions between the lipid bilayer membrane and the plasma components. Pegylated form of the drug is associated with a higher incidence of acute complications.

caspase-12 mediated cardiac apoptosis in both male and female rats. FEBS 2004, 577, 483-490. 10. Kaufmann S.H., Hengartner M.O.: Programmed cell death: alive and well in the new millennium. Trends Cell Biol 2001, 11, 526-534. 11. Mehmet H.: Caspases find a new place to hide. Nature 2000, 403, 29-30. 12. Mendocha J.: Localisation of different types of cell death in hepatic acinus depending on dose and time of adriamycin action. Thesis. Medical University in Lublin, Poland, 2009. 13. Muraoka S., Miura T.: Inactivation of mitochondrial succinatedehydrogenase by adriamycin

. Histol. 2009, 32:235-45. 10. Baylis C: Nitric oxide synthase derangements and hypertension in kidney disease. Curr. Opin. Nephrol. Hypertens. 2012, 21:1-6. 11. Sun YBY, Qu X, Zhang X, Caruana G, Bertram JF, Li: Glomerular endothelial cell injury and damage precedes that of podocytes in adriamycin-induced nephropathy. PLoS One 2013, 8:1-12. 12. Rangan GK, Wang Y, Harris DCH: Pharmacologic modulators of nitric oxide exacerbate tubulointerstitial inflammation in proteinuric rats. J Am Soc Nephrol. 2001, 12:1696-1705. 13. Muller V, Tain YL, Croker B, Baylis C: Chronic

/scripts/cder/daf/index.cfm?event=overview. process&ApplNo=020212 18. Boucek RJ, Jr, Steele A, Miracle A, Atkinson J. Effects of angiotensin-converting enzyme inhibitor on delayedonset doxorubicin-induced cardiotoxicity. Cardiovasc Toxicol. 2003;3:319-29. 19. Abd El-Aziz MA, Othman AI, Amer M, El-Missiry MA. Potential protective role of angiotensin-converting enzyme inhibitors captopril and enalapril against adriamycin-induced acute cardiac and hepatic toxicity in rats. J Appl Toxicol. 2001;21:469-73. 20. Hiona A, Lee AS, Nagendran J, Xie X, Connolly AJ, Robbins RC, et al. Pretreatment with angiotensin

References 1. Abdel-aleem S. et al.: Acute and chronic effects of adriamycin on fatty acid oxidation in isolated cardiac myocytes. J. Mol. Cell Cardiol., 29, 789, 1997. 2. Bachur N.R., Gordon S.L., Gee M.V.: A general mechanism for microsomal activation of quinone anticancer agents to free radicals. Cancer Res., 38, 1745, 1978. 3. Bizzi A. et al.: Adriamycin causes hyperlipemia as a consequence of nephrotoxicity. Toxicol. Lett., 18, 291, 1983. 4. Brown J.M.: The hypoxic cell: a target for selective cancer therapy- eighteenth Bruce F. Cain Memorial Award lecture

., Gutterridge J.M.C.: Free Radicals in Biology and Medicine. University Press, New York, 1999. 9. Hong Y.M., Kim H.S., Yoon H.: Serum lipid and fatty acid profiles in adriamycin-treated rats after administration of L-carnitine. Pediatr. Res., 51, 249, 2002. 10. Kerner J., et al.: Encyclopedia of biological chemistry., 2: 505-507, 2004. 11. Keyes G., Heimberg M.: Inf luence of thyroid status on lipid metabolism in the perfused rat liver. J. Clin. Invest., 64, 182, 1979. 12. Lebrecht D., et al.: Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain

. Minotti, P. Menna, E. Salvatorelli, G. Cairo and L. Gianni, Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity, Pharmacol. Rev. 56 (2004) 185-229; DOI: 10.1124/pr.56.2.6. 10. R. Nithipongvanitch, W. Ittarat, M. P. Cole, J. Tangpong, D. K. S. Clair and T. D. Oberley, Mitochondrial and nuclear p53 localization in cardiomyocytes: redox modulation by doxorubicin (Adriamycin)?, Antioxid. Redox Signal. 9 (2007) 1001-1008; DOI:10.1089/ars.2007.1632. 11. E. H. Herman and V. J. Ferrans, Amelioration of chronic

decrease triggered by subtoxic concentration of aclarubicin in human leukemia cell lines. Leuk. Res.   26 : 927-931. Rogalska A., Koceva-Chyła A. & Jóźwiak Z. (2008) Aclarubicin-induced ROS generation and collapse of mitochondrial membrane potential in human cancer cell lines. Chem. Biol. Interact.   176 : 58-70. Rogalska A., Marczak A. & Jóźwiak Z. (2008) Aklarubicyna - alternatywa dla komórek opornych na antracykliny I generacji. Post. Biol. Kom.   1 : 97-111. Shinohara K & Tanaka KR (1980) The effects of adriamycin (doxorubicin HCl) on human red blood cells

REFERENCES 1. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56:185-229. 2. Praet M, Pollakis G, Goormaghtigh E, Ruysschaert JM. Damages of the mitochondrial membrane in Adriamycin treated mice. Cancer Lett. 1984;25:89-96. 3. Zhou S, Starkov A, Froberg MK, Leino RL, Wallace KB. Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin. Cancer Res. 2001;61:771-7. 4. Arai M, Tomaru K, Takizawa T, Sekguchi

and [4Fe-4S]-reactivity of its secondary alcohol metabolite. Chem Res Toxicol. 2000;13:1336-41. 12. Halliwell B. Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol. 2006;141:312-22 13. Berthiaume JM, Wallace KB. Adriamycin-induced oxidative mitochondrial cardiotoxicity. Cell Biol Toxicol . 2007;23:15-25. 14. Wouters BG, Delahoussaye YM, Evans JW, Birrell GW, Dorie MJ, Wang J et al. Mitochondrial dysfunction after aerobic exposure to the hypoxic cytotoxin tirapazamine. Cancer Res . 2001;61:145-52. 15. Matysiak