Protective Effect of Captopril against Doxorubicin-Induced Oxidative Stress in Isolated Rat Liver Mitochondria Effect of captopril on doxorubicin toxicity
Iranian Journal of Pharmaceutical Sciences,
Vol. 6 No. 2 (2010),
1 April 2010
,
Page 91-98
https://doi.org/10.22037/ijps.v6.41255
Abstract
Doxorubicin (DOX) is an anthracycline antibiotic that has been used for a long time in therapy of an array of human malignancies either alone or in combination with other cytotoxic agents. The dose-dependent cardiotoxicity of DOX significantly limits its anticancer efficacies. Oxidative stress caused by enhanced production of reactive oxygen species is an important contributor to DOX mitochondrial toxicity. In the present study, DOX produced a significant elevation in TBARS, which is an indicator of lipid peroxidation, and significantly inhibited the activity of superoxide dismutase in rat liver mitochondria. Mitochondrial GSH dramatically decreased while GSSG was increased upon treatment of mitochondria by DOX. Co-treatment with captopril significantly reduced the lipid peroxidation in mitochondria and prevented
the inhibition of superoxide dismutase activity induced by DOX. Captopril also significantly increased the level of GSH in DOX-treated mitochondria. These results, therefore, suggest that captopril acts as an antioxidant and can protect the mitochondria against DOX-induced oxidative stress. This effect appears to be due to the sulfhydryl groups of captopril which may act as antioxidant or scavenger of
reactive oxygen species.
Keywords:
- Captopril
- Doxorubicin
- Oxidative stress
- Rat liver mitochondria
How to Cite
Hossein Niknahad, Alireza Taghdiri, Afshin Mohammadi-Bardbori, & Abbas Rezaeian Mehrabadi. (2010). Protective Effect of Captopril against Doxorubicin-Induced Oxidative Stress in Isolated Rat Liver Mitochondria: Effect of captopril on doxorubicin toxicity. Iranian Journal of Pharmaceutical Sciences, 6(2), 91–98. https://doi.org/10.22037/ijps.v6.41255
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[32] Pritsos CA, Sokoloff M, Gustafson DL. PZ-51 (Ebselen) in vivo protection against adriamycininduced mouse cardiac and hepatic lipid peroxidation and toxicity. Biochem Pharmacol 1992; 44: 839-41.
[33] Julka D, Sandhir R, Gill KD. Adriamycin-induced oxidative stress in central nervous system. Biochem Mol Biol Int 1993; 29:807-820.
[34] Liesuy SF, Arnaiz SL. Hepatotoxicity of mitoxantrone and ADR. Toxicology 1990; 63:187-98.
[35] Butterfield DM. B-Amyloid-associated free radical oxidative stress and neurotoxicity mplications for Alzheimer’s disease. Chem Res Toxicol 1997; 10: 495-506.
[36] Green P, Leeuwenburgh C. Mitochondrial dysfunction is an early indicator of ADR-induced apoptosis. Biochim Biophys Acta Mol Bas Dis 2002; 1588: 94-101.
[37] Frei B. Reactive oxygen species and antioxidant vitamins: mechanism of action. Am J Med 1994; 97 (suppl. 3A): 5S-13S.
[38] Keizer H, Pinedo H, Schuurhuis G, Joenje H.Doxorubicin (adriamycin): a critical review of free radical dependent mechanism of cytotoxicity.Pharmacol Ther 1990; 219-31.
[39] Fernandez-Checa JC, Kaplovitz N, Garcia-Ruitz C, Colell A. Mitochondrial glutathione:importance and transport. Semin Liver Dis 1998; 18: 389-401.
[40] Jaeschke H. Glutathione disulfide as index of oxidant stress in rat liver during hypoxia. Am J Physiol 1990; 258: 499-505.
[2] 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.
[3] Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction oxidative stress and risk of cardiovascular events in patients with coronary artery disease. Circ Res 2001; 104: 2673-8.
[4] Landmesser U, Spiekermann S, Dikalov S, Tatge H, Wilke R, Kohler C, Harrison DG, Hornig B, Drexler H. Vascular oxidative stress and endothelial dysfunction in patients with chronic heart failure: role of xanthine oxidase and extracellular superoxide dismutase. Circ Res 2002; 106: 3073-8.
[5] Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N, Takeshita A. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 2001; 88: 529 -35.
[6] Xu X, Persson HL, Richardson DR. Molecular pharmacology of the interaction of anthracyclines with iron. Mol Pharmacol 2005; 68: 261-71.
[7] Wallace KB. ADR-induced mitochondria cardiomyopathy. In Mitochondria in Pathogenesis. New York: Kluwer Academic/Plenum, 2001; pp. 465-86.
[8] Moore L, Landon EJ, Cooney DA. Inhibition of the cardiac mitochondrial calcium pump by adriamycin in vitro. Biochem Med 1977; 18: 131-8.
[9] Bachman E, Zbinden G. Effect of ADR and rubidazone on respiratory function and Ca2+ transport in rat heart mitochondria. Toxicol Lett 1979; 3: 29-34.
[10] Revis NW, Marusic N. Effects of ADR and its aglycone metabolite on calcium sequestration by rabbit heart liver and kidney mitochondria. Life Sci 1979; 25: 1055-64.
[11] Sokolove PM, Shinaberry RG. Na+-independent release of Ca2+ from rat heart mitochondria: induction by adriamycin aglycone. Biochem Pharmacol 1988; 37: 803-12.
[12] Solem LE, Henry TR, Wallace KB. Disruption of mitochondrial calcium homeostasis following chronic ADR administration. Toxicol Appl Pharmacol 1994; 129: 214-22.
[13] Chularojmontri L, Wattanapitayakul SK, Herunsalee A, Charuchongkolwongse S, Niumsakul S, Srichairat S. Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on ADR-induced cardiotoxicity. Biol Pharm Bull 2005; 28: 1165-71.
[14] Singal K, Li T, Kumar D, Danelisen I, Iliskovic N. Adriamycin-induced heart-failure: mechanism and modulation.Mol Cell Biochem 2000; 207: 77-85.
[15] Ghazi-Khansari M, Mohammadi-bardbori A.Captopril ameliorated mitochondrial toxicity due to paraquat. Toxicol In Vitro 2007; 21: 403-7.
[16] Mohammadi-Bardbori A, Ghazi-Khansari M.Alternative electron acceptors: proposed mechanism of paraquat mitochondrial toxicity. Environ Toxicol Pharmacol 2008; 26: 1-5.
[17] Parving HH, Lehnert H, Brochner-Mortensen J,Gomis R, Andersen S, Arner P. The effect or irbersartan on the development of diabetic nephrophathy in patients with type 2 diabetes. New Engl J Med 2001 ;345: 870-8.
[18] Park JB, Intengan HD, Schiffrin EL. Reduction of resistance artery stiffness by treatment with the AT1-receptor antagonist losartan in essential hypertension. JRAAS 2000; 1: 40-5.
[19] De Cavanagh E, Inserra F, Ferder L, Fraga C.Enalapril and captopril enhance glutathionedependent antioxidant defences in mouse tissues. Am J Physiol 2000; 278: 572-7.
[20] Rueckschloss U, Quinn MT, Holtz J, Morawietz H. Dose-dependent regulation of NADPH oxidase expression by angiotensin II in human endothelial cells: protective effect of angiotensin II type 1 receptor blockade in patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2002; 22: 1845-51.
[21] Ghazi-Khansari M, Mohammadi-bardbori A, Hosseini MJ. Using Janus green B to study paraquat toxicity in rat liver mitochondria: role of ACE inhibitors (thiol and nonthiol ACEi). Ann NY Acad Sci 2006; 1090: 98-107.
[22] Mohammadi-Bardbori A, Ghazi-Khansari M.Comparative measurement of cyanide and paraquat mitochondrial toxicity using two different mitochondrial toxicity assays. Toxicol Mech Methods 2007; 17: 1-5.
[23] Tamba M, Torreggiani A. Free radical scavenging and copper chelation: a potentially beneficial action of captopril. Free Radic Res 2000; 32:199-211.
[24] Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 1983; 65: 55-63.
[25] Babincova M, Altanerova V, Altaner E, Baeova Z, Babinec P. ADR mediated free iron release from ferritin magnetopartions for cancer therapy at higher temperatures: implications for cancer therapy. Eur Cell Mater 2002; 2: 140-1.
[26] Tietze F. Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione. Anal Biochem 1969; 27:502.
[27] Zachrias ES, Shelley RH, Pang NS. Protective effect of liposome-associated α-tocopherol against paraquat –induced acute lung toxicity. Biochem Pharmacol 1992; 44: 18118.
[28] Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem 1979; 72: 248-59.
[29] Perego P, Corna E, De Cesare M, Gatti L, Polizzi D, Pratesi G, Supino R, Zunino F. Role of apoptosis and apoptosis-related genes in cellular response and antitumor efficacy of anthracyclines.Curr Med Chem 2001; 8: 31-7.
[30] Zhong W, Oberley LW, Oberley TD, Yan T, Domann FE, St. Clair DK. Inhibition of cell growth and sensitization to oxidative damage by overexpression of manganese superoxide dismutase in rat glioma cells. Cell Growth Differ 1996; 7: 1175-86.
[31] Venkatesan N. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol 1998; 124: 425-7.
[32] Pritsos CA, Sokoloff M, Gustafson DL. PZ-51 (Ebselen) in vivo protection against adriamycininduced mouse cardiac and hepatic lipid peroxidation and toxicity. Biochem Pharmacol 1992; 44: 839-41.
[33] Julka D, Sandhir R, Gill KD. Adriamycin-induced oxidative stress in central nervous system. Biochem Mol Biol Int 1993; 29:807-820.
[34] Liesuy SF, Arnaiz SL. Hepatotoxicity of mitoxantrone and ADR. Toxicology 1990; 63:187-98.
[35] Butterfield DM. B-Amyloid-associated free radical oxidative stress and neurotoxicity mplications for Alzheimer’s disease. Chem Res Toxicol 1997; 10: 495-506.
[36] Green P, Leeuwenburgh C. Mitochondrial dysfunction is an early indicator of ADR-induced apoptosis. Biochim Biophys Acta Mol Bas Dis 2002; 1588: 94-101.
[37] Frei B. Reactive oxygen species and antioxidant vitamins: mechanism of action. Am J Med 1994; 97 (suppl. 3A): 5S-13S.
[38] Keizer H, Pinedo H, Schuurhuis G, Joenje H.Doxorubicin (adriamycin): a critical review of free radical dependent mechanism of cytotoxicity.Pharmacol Ther 1990; 219-31.
[39] Fernandez-Checa JC, Kaplovitz N, Garcia-Ruitz C, Colell A. Mitochondrial glutathione:importance and transport. Semin Liver Dis 1998; 18: 389-401.
[40] Jaeschke H. Glutathione disulfide as index of oxidant stress in rat liver during hypoxia. Am J Physiol 1990; 258: 499-505.
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