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Oleuropein Ameliorates Cisplatin-induced Hematological Damages Via Restraining Oxidative Stress and DNA Injury

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Abstract

The prevalence of cancer, in the world is increasing steadily. Despite intense research efforts, no approved therapy is yet available. Cisplatin is a chemotherapeutic drug but induces acute tissue injury. Oleuropein (OLE) is a major phenolic compound and used as a possible natural antioxidant, antimicrobial, and anticancer agent. We hypothesized that antioxidant activity of OLE may decrease cisplatin-induced oxidative stress and prevent to the development of chemotherapeutic complications including abnormality in hematological condition. Male Sprague Dawley rats were used in the experiments. Rats were randomly assigned to one of eight groups: control group; group treated with i.p. injection in a single dose of 7 mg/kg/day cisplatin; groups treated with 50, 100 and 200 mg/kg/day OLE (i.p.); and groups treated with OLE for 3 days starting at 24 h following cisplatin injection. First, hematological assessment was appreciated between control and experimental groups. Second, total oxidative stress (TOS) and total antioxidant capacity (TAC) levels of blood were measured by biochemical studies. In addition to this, oxidative DNA damage was determined by measuring as increases in 8-hydroxy-deoxyguanosine (8-OH-dG) adducts. The treatment with cisplatin elevated the TOS and 8-OH-dG levels that were then reversed by OLE. Reductions in antioxidant capacity with respect to corresponding controls were also restored by OLE treatment. These findings suggest that the OLE treatment against cisplatin-induced toxicity improves the function of blood cells and helps them to survive in the belligerent environment created by free radicals.

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References

  1. Li WB, Li Y, Yu C, He YM (2015) Reversal of multidrug resistance by the Chinese medicine Yiqi Jianpi Huaji decoction and the mechanism of action in human gastric cancer SGC7901/VCR Cells. Evid Based Complement Altern Med. doi:10.1155/2015/390812

    Google Scholar 

  2. Livingston RB (1989) Cisplatin in the treatment of solid tumors: effect of dose and schedule. J Natl Cancer Inst 81:724–725

    Article  CAS  PubMed  Google Scholar 

  3. Rasoulian B, Kaeidi A, Pourkhodadad S, Dezfoulian O, Rezaei M, Wahhabaghai H, Alirezaei M (2014) Effects of pretreatment with single-dose or intermittent oxygen on Cisplatin-induced nephrotoxicity in rats. Nephro Urol Mon. doi:10.5812/numonthly.19680

    Google Scholar 

  4. Cetin D, Hacımuftuoglu A, Tatar A, Turkez H, Togar B (2015) The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology. doi:10.1007/s10616-015-9896-3

    Google Scholar 

  5. Wheeler HE, Wing C, Delaney SM, Komatsu M, Dolan ME (2015) Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells. PLoS ONE. doi:10.1371/journal.pone.0118020

    Google Scholar 

  6. Kim HJ, Park DJ, Kim JH, Jeong EY, Jung MH, Kim TH, Yang JI, Lee GW, Chung HJ, Chang SH (2015) Glutamine protects against cisplatin-induced nephrotoxicity by decreasing cisplatin accumulation. J Pharmacol Sci 127:117–126

    Article  CAS  PubMed  Google Scholar 

  7. Osman AM, Telity SA, Damanhouri ZA, Al-Harthy SE, Al-Kreathy HM, Ramadan WS, Elshal MF, Khan LM, Kamel F (2015) Chemosensitizing and nephroprotective effect of resveratrol in cisplatin–treated animals. Cancer Cell Int. doi:10.1186/s12935-014-0152-2

    Google Scholar 

  8. Waseem M, Bhardwaj M, Tabassum H, Raisuddin S, Parvez S (2015) Cisplatin hepatotoxicity mediated by mitochondrial stress. Drug Chem Toxicol 38:452–459

    Article  CAS  PubMed  Google Scholar 

  9. Bhuvarahamurthy V, Balasubramanian N, Govindasamy S (1996) Effect of radiotherapy and chemoradiotherapy on circulating antioxidant system of human uterine cervical carcinoma. Mol Cell Biochem 158:17–23

    CAS  PubMed  Google Scholar 

  10. Takeuchi T, Nakajima M, Morimoto K (1996) Relationship between the intracellular reactive oxygen species and the induction of oxidative DNA damage in human neutrophil-like cells. Carcinogenesis 17:1543–1548

    Article  CAS  PubMed  Google Scholar 

  11. Satoh M, Kashihara N, Fujimoto S, Horike H, Tokura T, Namikoshi T, Sasaki T, Makino H (2003) A novel free radical scavenger, edarabone, protects against cisplatin-induced acute renal damage in vitro and in vivo. J Pharmacol Exp Ther 305:1183–1190

    Article  CAS  PubMed  Google Scholar 

  12. Saleh S, El-Demerdash E (2005) Protective effects of l-arginine against cisplatin-induced renal oxidative stress and toxicity: role of nitric oxide. Basic Clin Pharmacol Toxicol 97:91–97

    Article  CAS  PubMed  Google Scholar 

  13. Appenroth D, Frob S, Kersten L, Splinter FK, Winnefeld K (1997) Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats. Arch Toxicol 71:677–683

    Article  CAS  PubMed  Google Scholar 

  14. Sener G, Satiroglu H, Kabasakal L, Arbak S, Oner S, Ercan F, Keyer-Uysa M (2000) The protective effect of melatonin on cisplatin nephrotoxicity. Fundam Clin Pharmacol 14:553–560

    Article  CAS  PubMed  Google Scholar 

  15. Nisar S, Feinfeld DA (2002) N-acetylcysteine as salvage therapy in cisplatin nephrotoxicity. Ren Fail 24:529–533

    Article  PubMed  Google Scholar 

  16. Ali BH, Al Moundhri MS (2006) Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research. Food Chem Toxicol 44:1173–1183

    Article  CAS  PubMed  Google Scholar 

  17. Karimi G, Aghasizadeh M, Razavi M, Taghiabadi E (2011) Protective effects of aqueous and ethanolic extracts of Nigella sativa L. and Portulaca oleracea L. on free radical induced hemolysis of RBCs. Daru 19:295–300

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Obied HK, Karuso P, Prenzler PD, Robards K (2007) Novel secoiridoids with antioxidant activity from Australian olive mill waste. J Agric Food Chem 55:2848–2853

    Article  CAS  PubMed  Google Scholar 

  19. Bulotta S, Celano M, Lepore SM, Montalcini T, Pujia A, Russo D (2014) Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases. J Transl Med 12:219–225

    Article  PubMed  PubMed Central  Google Scholar 

  20. Casamenti F, Grossi C, Rigacci S, Pantano D, Luccarini I, Stefani M (2015) Oleuropein aglycone: a possible drug against degenerative conditions. In vivo evidence of its effectiveness against Alzheimer’s disease. J Alzheimer’s Dis 45:679–688

    CAS  Google Scholar 

  21. Al-Azzawie HF, Alhamdani MSS (2006) Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits. Life Sci 78:1371–1377

    Article  CAS  PubMed  Google Scholar 

  22. Omagari K, Kato S, Tsuneyama K, Hatta H, Sato M, Hamasaki M, Sadakane Y, Tashiro T, Fukuhata M, Miyata Y, Tamaru S, Tanaka K, Mune M (2010) Olive leaf extract prevents spontaneous occurrence of non-alcoholic steatohepatitis in SHR/NDmcr-cp rats. Pathology 42:66–72

    Article  CAS  PubMed  Google Scholar 

  23. Zukovec TD, Zivkovic L, Cabarkapa A, Djelic N, Bajic V, Dekanski D (2015) Dry olive leaf extract counteracts l-thyroxine-induced genotoxicity in human peripheral blood leukocytes in vitro. Oxid Med Cell Longev. doi:10.1155/2015/762192

    Google Scholar 

  24. Barbaro B, Toietta G, Maggio R, Arciello M, Tarocchi M, Galli A (2014) Effects of the olive-derived polyphenol oleuropein on human health. Int J Mol Sci 15:18508–18524

    Article  PubMed  PubMed Central  Google Scholar 

  25. National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington

    Google Scholar 

  26. Erel O (2004) A novel automated method to measure total anti-oxidant response against potential free radical reactions. Clin Biochem 37:112–119

    Article  CAS  PubMed  Google Scholar 

  27. Erel O (2005) A novel automated colorimetric method for measur-ing total oxidant status. Clin Biochem 38:1103–1111

    Article  CAS  PubMed  Google Scholar 

  28. Nie JH, Chen ZH, Liu X, Wu YW, Li JX, Cao Y, Hei TK, Tong J (2012) Oxidative damage in various tissues of rats exposed to radon. J Toxicol Environ Health 75:694–699

    Article  CAS  Google Scholar 

  29. Chan R, Mascarenhas L, Boles RG, Kerkar N, Genyk Y, Venkatramani R (2015) Hepatoblastoma in a patient with methylmalonic aciduria. Am J Med Genet A 167:635–638

    Article  Google Scholar 

  30. Gao LP, Li Z, Guo ZY, Zhao YM (2013) The effects of vitamin C on DDP-induced anemia in rats. Toxicol Mech Methods 23:383–388

    Article  CAS  PubMed  Google Scholar 

  31. Ghosh S, Bandyopadhyay S, Bhattacharya DK, Mandal C (2005) Altered erythrocyte membrane characteristics during anemia in childhood acute lymphoblastic leukemia. Ann Hematol 84:76–84

    Article  CAS  PubMed  Google Scholar 

  32. Niforou K, Cheimonidou C, Trougakos IP (2014) Molecular chaperones and proteostasis regulation during redox imbalance. Redox Biol 2:323–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Baliga R, Zhang Z, Baliga M, Ueda N, Shah SV (1998) In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int 53:394–401

    Article  CAS  PubMed  Google Scholar 

  34. Onat H, Inanc SE, Dalay N, Karaloglu D, Erturk N, Yasasever V (1993) Effect of cisplatin on erythropoietin and iron changes. Eur J Cancer 29:777–781

    Article  Google Scholar 

  35. Cazzola M (2000) Mechanisms of anaemia in patients with malignancy: implications for the clinical use of recombinant human erythropoietin. Med Oncol 17:11–16

    Google Scholar 

  36. Bosing B, Tunsmeyer J, Mischke R, Beyerbach M, Kastner SB (2012) Clinical usability and practicability of Alfaxalone for short-term anaesthesia in the cat after premedication with Buprenorphine. Tierarztl Prax Ausg K Kleintiere Heimtiere 40:17–25

    CAS  PubMed  Google Scholar 

  37. Harris AG, Sinitsina I, Messmer K (2002) Validation of OPS imaging for microvascular measurements during isovolumic hemodilution and low hematocrits. Am J Physiol Heart Circ Physiol 282:1502–1509

    Article  Google Scholar 

  38. Tedesco I, Russo M, Russo P, Iacomino G, Russo GL, Carraturo A, Faruolo C, Moio L, Palumbo R (2000) Antioxidant effect of red wine polyphenols on red blood cells. J Nutr Biochem 11:114–119

    Article  CAS  PubMed  Google Scholar 

  39. Lopez-Revuelta A, Sanchez-Gallego JI, Hernandez A, Sanchez-Yague J, Llanillo M (2006) Membrane cholesterol contents influence the protective effects of quercetin and rutin in erythrocytes damaged by oxidative stress. Chem Biol Interact 161:79–91

    Article  CAS  PubMed  Google Scholar 

  40. Li Y, Nishimura T, Teruya K, Maki T, Komatsu T, Hamasaki T, Kashiwagi T, Kabayama S, Shim SY, Katakura Y, Osada K, Kawahara T, Otsubo K, Morisawa S, Ishii Y, Gadek Z, Shirahata S (2002) Protective mechanism of reduced water against alloxan-induced pancreatic beta-cell damage: scavenging effect against reactive oxygen species. Cytotechnology 40:139–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Moghadam GT, Hosseini-Zijoud SM, Shayesteh TH, Ghasemi H, Ranjbar A (2014) Attenuation of cisplathin-induced toxic oxidative stress by propofol. Anesth Pain Med 4:14–21

    Google Scholar 

  42. Manna C, Galletti P, Cucciolla V, Moltedo O, Leone A, Zappia V (1997) The protective effect of the olive oil polyphenol (3,4-dihydroxyphenyl)-ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells. J Nutr Biochem 127:286–292

    CAS  Google Scholar 

  43. Manna C, Galletti P, Cucciolla V, Montedoro G, Zappia V (1999) Olive oil hydroxytyrosol protects human erythrocytes against oxidative damages. J Nutr Biochem 10:159–165

    Article  CAS  PubMed  Google Scholar 

  44. Hashimoto T, Ibi M, Matsuno K, Nakashima S, Tanigawa T, Yoshikawa T, Yabe-Nishimura C (2004) An endogenous metabolite of dopamine, 3,4-dihydroxyphenylethanol, acts as a unique cytoprotective agent against oxidative stress-induced injury. Free Radic Biol Med 36:555–564

    Article  CAS  PubMed  Google Scholar 

  45. Alirezaei M, Dezfoulian O, Neamati S, Rashidipour M, Tanideh N, Kheradmand A (2012) Oleuropein prevents ethanol-induced gastric ulcers via elevation of antioxidant enzyme activities in rats. J Physiol Biochem 68:583–592

    Article  CAS  PubMed  Google Scholar 

  46. Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE (2015) Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: a randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. doi:10.1200/JCO.2014.57.3105

    PubMed  PubMed Central  Google Scholar 

  47. Fabiani R, Rosignoli P, De Bartolomeo A, Fuccelli R, Servili M, Montedoro GF, Morozzi G (2008) Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. J Nutr 138:1411–1416

    CAS  PubMed  Google Scholar 

  48. De la Puerta R, Ruiz-Gutierrez V, Hoult JR (1999) Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil. Biochem Pharmacol 57:445–449

    Article  PubMed  Google Scholar 

  49. Zbidi H, Salido S, Altarejos J, Perez-Bonilla M, Bartegi A, Rosado JA, Salido GM (2009) Olive tree wood phenolic compounds with human platelet antiaggregant properties. Blood Cells Mol Dis 42:279–285

    Article  CAS  PubMed  Google Scholar 

  50. Hu Z, Zeng Q, Zhang B, Liu H, Wang W (2014) Promotion of p53 expression and reactive oxidative stress production is involved in zerumbone-induced cisplatin sensitization of non-small cell lung cancer cells. Biochimie 107:257–262

    Article  CAS  PubMed  Google Scholar 

  51. Rybak LP, Husain K, Morris C, Whitworth C, Somani S (2000) Effect of protective agents against cisplatin ototoxicity. Am J Otol 21:513–520

    CAS  PubMed  Google Scholar 

  52. Wu Q, Ni X (2015) ROS-mediated DNA methylation pattern alterations in carcinogenesis. Curr Drug Targets 16:13–19

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was funded by Atatürk University (Grant Number: BAP- 2015/94).

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, Atatürk University, Erzurum, Turkey

    Fatime Geyikoğlu, Murat Bakır, Kübra Koç, Mir Khalil Hosseinigouzdagani & Salim Çeriğ

  2. Üzümlü Vocational School, Erzincan University, Erzincan, Turkey

    Suat Çolak

  3. Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey

    Hasan Türkez

  4. Department of Pharmacy, University “G. d’Annunzio” Chieti-Pescara, Chieti, Italy

    Hasan Türkez

  5. Department of Biology, Faculty of Art and Science, Erzincan University, Erzincan, Turkey

    Merve Sönmez

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  1. Fatime Geyikoğlu
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Correspondence to Fatime Geyikoğlu.

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Geyikoğlu, F., Çolak, S., Türkez, H. et al. Oleuropein Ameliorates Cisplatin-induced Hematological Damages Via Restraining Oxidative Stress and DNA Injury. Indian J Hematol Blood Transfus 33, 348–354 (2017). https://doi.org/10.1007/s12288-016-0718-3

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