Abstract
Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its’ analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2′:6′,2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied. Cisplatin and the analogues were perfused at concentration of 10−6 and 10−5 M during 30 min. The results of this study showed that examined platinum complexes had different ability to induce oxidative stress of isolated perfused rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and 2,2′:6′,2″-terpyridine, related to amino ligands (cisplatin) directly influenced the strength to induce production of oxidative stress biomarkers. Introducing 2,2′:6′,2″-terpyridine ligands provoked the smallest changes in antioxidant enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that undoubtedly indicated that this complex had the lowest impact on redox status in heart tissue. These findings may be useful in synthesis of novel platinum analogues with lower potential for oxidative stress induction. However, the fact that platinum complexes could induce toxic effects in the heart by other mechanisms should be taken into the consideration.
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Kart A, Cigremis Y, Karaman M, Ozen H (2010) Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit. Exp Toxicol Pathol 62:45–52. doi:10.1016/j.etp.2009.02.066
Yousef MI, Saad AA, El-Shennawy LK (2009) Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats. Food Chem Toxicol 47:1176–1183. doi:10.1016/j.fct.2009.02.007
Paolicchi A, Sotiropuolou M, Perego P, Daubeuf S, Visvikis A, Lorenzini E, Franzini M, Romiti N, Chieli E, Leone R, Apostoli P, Colangelo D, Zunino F, Pompella A (2003) Gamma-glutamyl transpeptidase catalyses the extracellular detoxification of cisplatin in a human cell line derived from the proximal convoluted tubule of the kidney. Eur J Cancer 39:996–1003
Townsend DM, Tew KD, He L, King JB, Hanigan MH (2009) Role of glutathione S-transferase Pi in cisplatin-induced nephrotoxicity. Biomed Pharmacother 63:79–85. doi:10.1016/j.biopha.2008.08.004
Yang Z, Schumaker LM, Egorin MJ, Zuhowski EG, Guo Z, Cullen KJ (2006) Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mitochondrial membrane of head and neck squamous cell carcinoma: possible role in apoptosis. Clin Cancer Res 12:5817–5825. doi:10.1158/1078-0432.CCR-06-1037
Dzagnidze A, Katsarava Z, Makhalova J, Liedert B, Yoon MS, Kaube H, Limmroth V, Thomale J (2007) Repair capacity for platinum-DNA adducts determines the severity of cisplatin-induced peripheral neuropathy. J Neurosci 27:9451–9457. doi:10.1523/JNEUROSCI.0523-07.2007
Kintzel PE (2001) Anticancer drug-induced kidney disorders. Drug Saf 24:19–38
Rabik CA, Dolan ME (2007) Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 33:9–23. doi:10.1016/j.ctrv.2006.09.006
Raja W, Mir MH, Dar I, Banday MA, Ahmad I (2013) Cisplatin induced paroxysmal supraventricular tachycardia. Indian J Med Paediatr Oncol 34:330–332. doi:10.4103/0971-5851.125262
Guglin M, Aljayeh M, Saiyad S, Ali R, Curtis AB (2009) Introducing a new entity: chemotherapy-induced arrhythmia. Europace 11:1579–1586. doi:10.1093/europace/eup300
Dolci A, Dominici R, Cardinale D, Sandri MT, Panteghini M (2008) Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use. Am J Clin Pathol 130:688–695. doi:10.1309/AJCPB66LRIIVMQDR
Khan S, Chen CL, Brady MS, Parameswaran R, Moore R, Hassoun H, Carvajal RD (2012) Unstable angina associated with cisplatin and carboplatin in a patient with advanced melanoma. J Clin Oncol 30:e163–e164. doi:10.1200/JCO.2011.38.7852
Ryberg M (2012) Recent advances in cardiotoxicity of anticancer therapies. Am Soc Clin Oncol Educ Book 2012:555–559. doi:10.14694/EdBook_AM.2012.32.555
Dugbartey GJ, Peppone LJ, de Graaf IA (2016) An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures. Toxicology 371:58–66. doi:10.1016/j.tox.2016.10.001
El-Awady ESE, Moustafa YM, Abo-Elmatty DM, Radwan A (2011) Cisplatin-induced cardiotoxicity: mechanisms and cardioprotective strategies. Eur J Pharmacol 650:335–341. doi:10.1016/j.ejphar.2010.09.085
Ma H, Jones KR, Guo R, Xu P, Shen Y, Ren J (2010) Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: role of endoplasmic reticulum stress. Clin Exp Pharmacol Physiol 37:460–465. doi:10.1111/j.1440-1681.2009.05323.x
Chirino YI, Pedraza-Chaverri J (2009) Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol 61:223–242. doi:10.1016/j.etp.2008.09.003
Baek SM, Kwon CH, Kim JH, Woo JS, Jung JS, Kim YK (2003) Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal proximal tubular epithelial cells. J Lab Clin Med 142:178–186. doi:10.1016/S0022-2143(03)00111-2
Weijl NI, Hopman GD, Wipkink-Bakker A, Lentjes EG, Berger HM, Cleton FJ, Osanto S (1998) Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Ann Oncol 9:1331–1337
Rosic G, Selakovic D, Joksimovic J, Srejovic I, Zivkovic V, Tatalović N, Orescanin-Dusic Z, Mitrovic S, Ilic M, Jakovljevic V (2016) The effects of N-acetylcysteine on cisplatin-induced changes of cardiodynamic parameters within coronary autoregulation range in isolated rat hearts. Toxicol Lett 242:34–46. doi:10.1016/j.toxlet.2015.11.028
Chowdhury S, Sinha K, Banerjee S, Sil PC (2016) Taurine protects cisplatin induced cardiotoxicity by modulating inflammatory and endoplasmic reticulum stress responses. BioFactors 42:647–664. doi:10.1002/biof.1301
Najam R, Bano N, Mirza T, Hassan S (2014) Adverse effects on cardiovascular status and lipid levels of albino Wistar rats treated with cisplatin and oxaliplatin in combination with 5 Fluorouracil. Pak J Pharm Sci. 27(5):1409–1418
Dasari S, Tchounwou PB (2014) Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 740:364–378. doi:10.1016/j.ejphar.2014.07.025
Rixe O, Ortuzar W, Alvarez M, Parker R, Reed E, Paull K, Fojo T (1996) Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute’s Anticancer Drug Screen panel. Biochem Pharmacol 52:1855–1865
Zhang CX, Lippard SJ (2003) New metal complexes as potential therapeutics. Curr Opin Chem Biol 7:481–489
Bugarčić ŽD, Bogojeski J, Petrović B, Hochreuther S, van Eldik R (2012) Mechanistic studies on the reactions of platinum(II) complexes with nitrogen- and sulfur-donor biomolecules. Dalton Trans 41:12329–12345. doi:10.1039/c2dt31045g
Bugarcic ZD, Heinemann FW, van Eldik R (2004) Substitution reactions of [Pt(terpy)X]2+ with some biologically relevant ligands. Synthesis and crystal structure of [Pt(terpy)(cyst-S)](ClO4)2.0.5H2O and [Pt(terpy)(guo-N7)](ClO4)2.0.5guo.1.5H2O. Dalton Trans 21:279–286. doi:10.1039/b311056g
Pouna P, Bonoron-Adèl S, Gouverneur G, Tariosse L, Besse P, Robert J (1995) Evaluation of anthracycline cardiotoxicity with the model of isolated, perfused rat heart: comparison of new analogues versus doxorubicin. Cancer Chemother Pharmacol 35:257–261
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite and [15 N] nitrate in biological fluids. Anal Biochem 126:131–138
Auclair C, Voisin E (1985) Nitroblue tetrazolium reduction. In: Ra Greenvvald (ed) Handbook of methods for oxygen radical research. CRC Press Une, Boca Raton, pp 123–132
Pick E, Keisari Y (1980) A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Methods 38:161–170
Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Aebi H (1984) Catalase in vitro. Methods Enzymol 105(121–126):25
Beutler E (1984) Superoxide dismutase. In: Beutler E (ed) Red cell metabolism a manual of biochemical methods. Grune & Stratton, Philadelphia, pp 83–85
Saksida T, Nikolic I, Vujicic M, Nilsson UJ, Leffler H, Lukic ML et al (2013) Galectin-3 deficiency protects pancreatic islet cells from cytokine-triggered apoptosis in vitro. J Cell Physiol 228:1568–1576
Galanski M, Keppler BK (1995) Synthesis and characterization of new ethylenediamine platinum(IV) complexes containing lipophilic carboxylate ligands. Metal Drugs 2:57–63
Demkow U, Biatas-Chromiec B, Stelmaszczyk-Emmel A, Radzikowska E, Wiatr E, Radwan-Rohrenschef P, Szturmowicz M (2011) The cardiac markers and oxidative stress parameters in advanced non-small cell lung cancer patients receiving cisplatin-based chemotherapy. EJIFCC 22:6–15
Mythili Y, Sudharsan PT, Selvakumar E, Varalakshmi P (2004) Protective effect of dl-alpha-lipoic acid on cyclophosphamide induced oxidative cardiac injury. Chem Biol Interact 151:13–19. doi:10.1016/j.cbi.2004.10.004
El-Sawalhi MM, Ahmed LA (2014) Exploring the protective role of apocynin, a specific NADPH oxidase inhibitor, in cisplatin-induced cardiotoxicity in rats. Chem Biol Interact 207:58–66. doi:10.1016/j.cbi.2013.11.008
Saleh RM, Awadin WF, El-Shafei RA, Elseady YY, Wehaish FE, Elshal MF (2015) Cardioprotective role of tadalafil against cisplatin-induced cardiovascular damage in rats. Eur J Pharmacol 765:574–581. doi:10.1016/j.ejphar.2015.09.015
Lushchak VI (2012) Glutathione homeostasis and functions: potential targets for medical interventions. J Amino Acid 2012:736837. doi:10.1155/2012/736837
Abdellatief SA, Galal AA, Farouk SM, Abdel-Daim MM (2017) Ameliorative effect of parsley oil on cisplatin-induced hepato-cardiotoxicity: a biochemical, histopathological, and immunohistochemical study. Biomed Pharmacother 86:482–491. doi:10.1016/j.biopha.2016.12.038
Hussein A, Ahmed AA, Shouman SA, Sharawy S (2012) Ameliorating effect of dl-α-lipoic acid against cisplatin-induced nephrotoxicity and cardiotoxicity in experimental animals. Drug Discov Ther 6:147–156
Warner BB, Stuart L, Gebb S, Wispé JR (1996) Redox regulation of manganese superoxide dismutase. Am J Physiol 271(1 Pt 1):L150–L158
Kim JW, Sahm H, You J, Wang M (2010) Knock-down of superoxide dismutase 1 sensitizes cisplatin-resistant human ovarian cancer cells. Anticancer Res 30(7):2577–2581
Fridovich I (1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64:97–112
Valdivia A, Pérez-Alvarez S, Aroca-Aguilar JD, Ikuta I, Jordán J (2009) Superoxide dismutases: a physiopharmacological update. J Physiol Biochem. 65(2):195–208
Landriscina M, Maddalena F, Laudiero G, Esposito F (2009) Adaptation to oxidative stress, chemoresistance, and cell survival. Antioxid Redox Signal 11(11):2701–2716. doi:10.1089/ars.2009.2692
Stohs SJ, Bagchi D (1995) Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18:321–336
Gardner CR, Laskin JD, Dambach DM, Sacco M, Durham SK, Bruno MK, Cohen SD, Gordon MK, Gerecke DR, Zhou P, Laskin DL (2002) Reduced hepatotoxicity of acetaminophen in mice lacking inducible nitric oxide synthase: potential role of tumor necrosis factor-alpha and interleukin-10. Toxicol Appl Pharmacol 184:27–36
Harstad EB, Klaassen CD (2002) iNOS-null mice are not resistant to cadmium chloride-induced hepatotoxicity. Toxicology 175:83–90
Nishikawa M, Nagatomi H, Nishijima M, Ohira G, Chang BJ, Sato E, Inoue M (2001) Targeting superoxide dismutase to renal proximal tubule cells inhibits nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice. Cancer Lett 171:133–138
Davis CA, Nick HS, Agarwal A (2001) Manganese superoxide dismutase attenuates Cisplatin-induced renal injury: importance of superoxide. J Am Soc Nephrol 12:2683–2690
Pecorelli A, Bocci V, Acquaviva A, Belmonte G, Gardi C, Virgili F, Ciccoli L, Valacchi G (2013) NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells. Toxicol Appl Pharmacol 267(1):30–40
Surh YJ, Kundu JK, Na HK (2008) Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 74(13):1526–1539
Liu Q, Si T, Xu X, Liang F, Wang L, Pan S (2015) Electromagnetic radiation at 900 MHz induces sperm apoptosis through bcl-2, bax and caspase-3 signaling pathways in rats. Reprod Health 12:65. doi:10.1186/s12978-015-0062-3
Liu Q, Hu S, He Y, Zhang J, Zeng X, Gong F, Liang L (2017) The protective effects of Zhen-Wu-Tang against cisplatin-induced acute kidney injury in rats. PLoS ONE 12(6):e0179137. doi:10.1371/journal.pone.0179137
Howe-Grant ME, Lippard SJ (1980) Aqueous platinum(II) chemistry: binding to biological macromolecules. In: Siegel H (ed) Metal ions in biological systems, 11th edn. Marcel Dekker, New York, pp 63–125
Summa N, Schiessl W, Puchta R, van Eikema Hommes N, van Eldik R (2006) Thermodynamic and kinetic studies on reactions of Pt(II) complexes with biologically relevant nucleophiles. Inorg Chem 45:2948–2959. doi:10.1021/ic051955r
Bogojeski J, Bugarčić ŽD, Puchta R, Eldik R (2010) Kinetic studies on the reactions of different bifunctional platinum(II) complexes with selected nucleophiles. Eur JIC 2010:5439–5445
Hofmann A, Jaganyi D, Munro OQ, Liehr G, van Eldik R (2003) Electronic tuning of the lability of Pt(II) complexes through pi-acceptor effects. Correlations between thermodynamic, kinetic, and theoretical parameters. Inorg Chem 42:1688–1700
Hofmann A, Dahlenburg L, van Eldik R (2003) Cyclometalated analogues of platinum terpyridine complexes: kinetic study of the strong sigma-donor cis and trans effects of carbon in the presence of a pi-acceptor ligand backbone. Inorg Chem 42:6528–6538
Petrovic BV, Djuran MI, Bugarcic ZD (1999) Binding of platinum(II) to some biologically important thiols. Met Based Drugs 6:355–360
Jaganyi D, Hofmann A, van Eldik R (2001) Controlling the lability of square-planar Pt(II) complexes through electronic communication between π-acceptor ligands. Angew Chem Int Ed Engl 40:1680–1683
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Stojic, I.M., Zivkovic, V.I., Srejovic, I.M. et al. Cisplatin and cisplatin analogues perfusion through isolated rat heart: the effects of acute application on oxidative stress biomarkers. Mol Cell Biochem 439, 19–33 (2018). https://doi.org/10.1007/s11010-017-3132-8
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DOI: https://doi.org/10.1007/s11010-017-3132-8