In the present study, we aimed to determine the oxidative damage in rat heart tissue induced by ruthenium(II)-NHC (Ru) and gold(I)-NHC (Au) complexes which have anticarcinogenic effects and not used clinically yet. For this purpose, 35 Sprague-Dawley rats were randomly divided into 5 equal groups. In the control group, rats treated with saline, Ru and Au complexes were intraperitoneally given high (10 mg/kg) and low (5 mg/kg) doses as only one administration. The animals were killed, and heart tissues were taken on day 10 of the drug administration for the determination of the biochemical parameters (malondialdehyde, superoxide dismutase, reduced glutathione and catalase levels). It was determined that both Ru and Au complexes treatment significantly caused oxidative damage compared to the control group. Additionally, it was shown that Au treatment caused more adverse effects than Ru treatment. Also, it was clearly found that the occurred effects were generally determined in a dose-dependent manner. In conclusion, when these compounds synthesized for the treatment of cancer were used, they caused oxidative damage in heart tissue. However, Ru complex could be preferred for cancer treatment in terms of user safety.
Aebi H. ( 1984) Catalase in vitro assay methods. Methods in Enzymology105: 121-126.
2.
Babu E., Gopalakrishnan VK, Sriganth IN, Gopalakrishnan R., and Sakthisekaran D. (1995) Cis-platin ınduced nephrotoxicity and the modulating effect of glutathione ester. Molecular and Cellular Biochemistry144: 7-11.
3.
Ciftci O., Ozdemir I., Vardi N., and Gurbuz N. ( 2010) Novel platinum-N-heterocyclic carbene complex is more cardiotoxic than cis-platin in rats. Human Experimental Toxicology DOI: 10.1177/0960327110390064.
Custódio JB, Cardoso CM, Santos MS, Almeida LM, Vicente JA, and Fernandes MA ( 2009) Cis-platin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: prevention by thiol group protecting agents. Toxicology2;259:18-24.
6.
Demir S., Özdemir İ., and Çetinkaya B. (2009) Synthesis and catalytic properties of novel ruthenium N-heterocyclic-carbene complexes. The Journal of Organometallic Chemistry694: 4025-4031.
7.
Hara M., Yoshida M., Nishijima H., Yokosuka M., Iigo M., Ohtani-Kaneko R., et al. (2001) Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin-ınduced nephrotoxicity in rats. Journal of Pineal Research30: 129-138.
8.
Hartinger CG and Dyson PJ ( 2009) Bioorganometallic chemistry-from teaching paradigms to medicinal applications. Chemical Society Reviews38: 391-401.
9.
Kreuser ED, Keppler BK, Berdel WE, Piest A., and Thiel E. ( 1992) Synergistic antitumor interactions between newly synthesized ruthenium complexes and cytokines in human colon carcinoma cell lines. Seminars in Oncology19: 73-81.
10.
Li H. and Qian ZM ( 2002) Transferrin/transferrin receptor-mediated drug delivery . Medical Research Reviews22: 225-250.
11.
Lowry OH, Rosebrough NJ, Farr AL, and Randall RJ ( 1951) Protein measurement with pholin phenol reagent. Journal of Biological Chemistry193: 265-275.
12.
Luo J., Tsuji T., Yasuda H., Sun Y., Fujigaki Y., and Hishida A. ( 2008) The molecular mechanisms of the attenuation of cisplatin-induced acute renal failure by N-acetylcysteine in rats. Nephrology Dialysis Transplant23: 2198-2205.
13.
Mansour MA, Mostafa AM, Nagi NM, Khattab MM, and Al-Shabanah OA ( 2002) Protective effect of aminoguanidine against nephrotoxicity ınduced by cisplatin in normal rats. Comparative Biochemistry and Physiology Part C132: 123-128.
14.
Mazumder UK, Gupta M., Karki SS, Bhattacharya S., Rathinasamy S., and Sivakumar T. ( 2005) Synthesis and pharmacological activities of some mononuclear Ru(II) complexes. Bioorganic & Medicinal Chemistry13: 5766-5773.
15.
McKeage MJ, Maharaj L., and Berners-Price SJ (2002) Mechanisms of cytotoxicity and antitumor activity of gold(I) phosphine complexes: the possible role of mitochondria. Coordination Chemistry Reviews232: 127-135.
16.
Mirabelli CK, Hill DT, Faucette LF, McCabe FL, Girard GR, Bryan DB, et al. (1987) Antitumor activity of bis (diphenylphosphino) alkanes, their gold(I) coordination complexes, and related compounds. Journal of Medical Chemistry30: 2181-2190.
17.
Mirabelli CK, Johnson RK, Hill DT, Faucette LF, Girard GR, Keu GY, et al. (1986) Correlation of the in vitro cytotoxic and in vivo antitumor activities of gold(I) coordination complexes. Journal of Medical Chemistry29: 218-223.
18.
Montjean D., Ménézo Y., Benkhalifa M., Cohen M., Belloc S., Cohen-Bacrie P., and De Mouzon J. ( 2010) Malonaldehyde formation and DNA fragmentation: two independent sperm decays linked to reactive oxygen species. Zygote18: 265-268.
19.
Ozdemir İ., Temelli N., and Günal S., and Demir S. ( 2010) Gold(I) complexes of N-heterocyclic carbene ligands containing benzimidazole: Synthesis and antimicrobial activity. Molecules15: 2203-2210.
20.
Sadzuka Y., Shoji T., and Takino Y. ( 1992) Mechanism of the increase in lipid peroxide induced by cisplatin in the kidneys of rats. Toxicology Letters62: 293-300.
21.
Schiller HJ, Reilly PM, and Bulkley GB ( 1993) Tissue perfusion in critical illnesses. Antioxidant therapy . Critical Care Medicine21: 92-102.
22.
Sedlak J. and Lindsay RH ( 1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry25: 192-205.
23.
Sheikh-Hamad D., Timmins K., and Jalali Z. ( 1997) Cisplatin ınduced renal toxicity: possible reversal by N-cetylcysteine treatment. Journal of the American Society of Nephrology8: 1640-1644.
24.
Shimeda Y., Hirotani Y., Akimoto Y., Shindou K., Ijiri Y., Nishihori T., and Tanaka K. ( 2005) Protective effects of capsaicin against cisplatin-induced nephrotoxicity in rats. Biological and Pharmacological Bulletin28: 1635-1638.
25.
Simon TM, Kunishima DH, Vilbert GJ, and Lorber A. ( 1981) Screen trial with a coordinated gold compound auranofin using mouse lymphocytic leukemia P388. Cancer Research41: 94-97.
26.
Sun Y., Oberley LW, and Li Y. ( 1988) A simple method for clinical assay of superoxide dismutase . Clinical Chemistry34: 497-500.
27.
Wang J., He D., Zhang Q., Han Y., Jin S., and Qi F. ( 2009) Resveratrol protects against Cisplatin induced cardio-toxicity by alleviating oxidative damage. Cancer Biotheraphy and Radiopharmaceuticals24: 675-680.
28.
Yagi K. ( 1998) Simple assay for the level of total lipid peroxides in serum or plasma. Methods in Molecular Biology108: 101-106.
29.
Yüce A., Ateşşahin A., Ceribaşi AO, and Aksakal M. ( 2007) Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats. Basic Clinical Pharmacology and Toxicology101: 345-349.
