Ratlarda siklofosfamidin sebep olduğu kardiyotoksisitede propolisin koruyucu rolü

Abstract

Çalışmada, kanser ve malignant olmayan hastalıkların tedavisinde etkili olduğu kanıtlanmış geniş klinik kullanımlı
alkilleyici kemoterapötik bir ilaç olan siklofosfamid (CP)’in kardiyotoksisitesi üzerine propolisin etkileri incelenmiştir. Ratlar; kontrol
grubu, propolis uygulanan grup (200 mg/kg/gün gavaj, 7 gün), CP uygulanan grup (150 mg/kg i.p. tek doz) ve CP+propolis uygulanan
grup şeklinde 4 gruba ayrılmıştır. Propolis uygulamasına CP uygulamasından 2 gün önce başlanmış ve 7 gün süre ile devam edilmiştir.
Kalp dokuları biyokimyasal ve histopatolojik incelemeler için alınmıştır. Kalp dokusunda malondialdehid (MDA), redükte glutatyon
(GSH) düzeyleri, katalaz (CAT), glutatyon peroksidaz (GSH-Px), glutatyon-S-transferaz (GST) ve süperoksit dismutaz (SOD)
aktiviteleri tayini yapılmıştır. Histopatolojik inceleme için kalp dokusu örnekleri uygun yöntemlerle hazırlanıp Masson’nun Trichrome
ve Hematoksilen-Eozin tekniği ile boyandıktan sonra incelenmiştir. CP uygulanan grupta MDA, GSH düzeyleri ve CAT aktivitesinde
artış, GSH-Px, GST ve SOD aktivitelerinde düşüş saptanmıştır (p<0.05). CP+propolis uygulanan grupta MDA, GSH düzeyleri ve
antioksidan enzim aktivitelerinin normal düzeylere ulaştığı gözlenmiştir. Propolis uygulanan grup ile CP+propolis uygulanan gruplarda
istatistiksel olarak önemli bir değişiklik gözlenmemiştir. Histopatolojik incelemelerde kontrol grubunda kalp dokusuna ait kesitler
normal yapıda gözlenmiştir. Propolis uygulanan grupta kalp dokusu kontrol grubu ile benzer yapı göstermiştir. CP uygulanan grupta
kalp kası lifleri arasında bazı alanlarda hemoraji ve vasküler konjesyon gözlenmiştir. CP+propolis uygulaması yer yer vasküler
konjesyona yol açmıştır. CP’e bağlı kardiyotoksisitenin patogenezinde oksidatif stresin rol oynayabileceği, propolisin CP’e bağlı yan
etkileri azaltabileceği görülmektedir.  

Keywords

• Antioksidan,kalp,malondialdehid,propolis,siklofosfamid

References

1. 1. Aebi H (1974): Catalase. 673-678. In: Bergmeyer HU (Ed). Methods of enzymatic analysis. 2nd English ed. Weinheim: Verlag Chemie.
2. 2. Aktürk E, Kurtoğlu E, Harputluoğlu H (2011): Kanser ilaçlarının kardiyovasküler yan etkileri: bu yan etkiler nasıl belirlenmeli, tedavi ve takip nasıl yapılmalı? İnönü Üniversitesi Tıp Fakültesi Dergisi 2011; 18(2), 137-142.
3. 3. Asiri Y (2010): Probucol attenuates cyclophosphamideinduced oxidative apoptosis, p53 and bax signal expression in rat cardiac tissues. Oxid Med Cell Longev, 3(5), 308- 316.
4. 4. Bansal AK, Bansal M, Soni G ve ark. (2005): Modulation of N-nitrosodiethylamine (NDEA) induced oxidative stress by vitamin E in rat erythrocytes. Hum Exp Toxicol, 24(6), 297-302.
5. 5. Bansal AK, Bansal M, Soni G ve ark. (2005): Protective role of vitamin E pre-treatment on Nnitrosodiethylamine induced oxidative stress in rat liver. Chem Biol Interact, 156(2-3), 101-111.
6. 6. Beutler E (1984): Red cell metabolism. 160. A manual of biochemical methods. Grune and Starton (Editors)2nd Edition, New York.
7. 7. Block KI, Koch AC, Mead MN ve ark. (2007): Impact of antioxidant suplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials. Cancer Treat Rev, 33(5), 407-418.
8. 8. Braverman AC, Antin JH, Plappert MT ve ark. (1991): Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol, 9, 1215-1223.

9. 9. Cetik S, Ayhancı A, Şahintürk V (2015): Protective effect of carvacrol against oxidative stress and heart injury in cyclophosphamide-induced cardiotoxicity in rat. Br Arch Biol Technol, 58(4), 596-76.
10. 10. Chakraborty M, Kamath JV, hattacharjee A (2014): Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against cyclophosphamide-induced myocardial damage. Toxicol Int, 21(2), 196.
11. 11. Chunyi, G, Jian, Z, Yueran ve ark. (2000): Experimental and clinical studies on the effect of extract of propolis on decreasing the toxicity of chemotherapeutant. Chinese J Biochem Pharm, 2, 90-92.
12. 12. Ellman GL, Courtney KD, Andres V ve ark. (1961): A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol, 7, 88-95.
13. 13. El-Naggar SA, Alm-Eldeen AA, Germoush MO ve ark. (2015): Ameliorative effect of propolis against cyclophosphamide-induced toxicity in mice. Pharm Biol, 53(2), 235-241.
14. 14. Erkurt ME, Kuku İ, Kaya E ve ark. (2009): Kanser kemoterapisi ve böbrek. İnönü Üniversitesi Tıp Fakültesi Dergisi, 16(1), 63-68.
15. 15. Fatani AG, Darweesh AQ, Rizwan L ve ark. (2010): Carnitine deficiency aggravates cyclophosphamideinduced cardiotoxicity in rats. Chemotherapy, 56(1), 71-81.
16. 16. Fisher-Wellman K, Bell HK, Bloomer RJ (2009): Oxidative stress and antioxidant defense mechanisms linked to exercise during cardiopulmonary and metabolic disorders. Oxid Med Cell Longev, 2, 43-51.
17. 17. Floyd JD, Nguyen DT, Lobins RL ve ark. (2005): Cardiotoxicity of cancer therapy. J Clin Oncol, 23, 7685- 7696.
18. 18. Friedman HS, Colvin OM, Aisaka K ve ark. (1990): Glutathione protects cardiac and skeletal muscle from cyclophosphamide-induced toxicity. Cancer Res, 50(8), 2455-2462.
19. 19. Fuliang HU, Hepburn HR, Xuan H ve ark. (2005): Effects of propolis on blood glucose, blood lipid and free radicals in rats with diabetes mellitu. Pharmacol Res, 51(2), 147–152.
20. 20. Gershwin ME, Goetzl EJ, Steinberg AD (1974): Cyclophosphamide: use in practice. Ann Intern Med, 80, 531-540.
21. 21. Goldberg MA, Antin JH, Guinan EC ve ark. (1986): Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor. Blood, 68, 1114-1118.
22. 22. Gunes S, Ayhanci A, Sahinturk V ve ark. (2017): Carvacrol attenuates cyclophosphamide-induced oxidative stress in rat kidney. Can J Physiol Pharmacol, 95(7), 844- 849.
23. 23. Habig WH, Pabst MJ, Jakoby WB (1974): Glutathione Stransferases. The first enzymatic step in mercapturic acid formation. J Biol Chem, 249, 130-139.
24. 24. Horacek JM (2011): Biomarkers of cardiac injury in detection of cardiotoxicity induced by chemotherapeutic agents. Mil Med Sci Lett, 80, 103-117.
25. 25. Ince S, Kucukkurt I, Demirel HH ve ark. (2014): Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere, 108, 197-204.
26. 26. Janero DR, Hreniuk D, Sharif HM (1991): Hydrogen peroxide- induced oxidative stress to the mammalian heartmuscle cell (cardiomyocyte): lethal peroxidative membrane injury. J Cell Physiol, 149, 347-64.
27. 27. Karagöz Y (2015): Etkileşimli (İnteraksiyonlu) Varyans Analizi. 277-284. Güncellenmiş 2. Basım, SPSS 22 Uygulamalı Biyoistatistik. Nobel, Ankara.
28. 28. Liu CC, Hsu JM, Kuo LK ve ark. (2013): Caffeic acid phenethyl ester as an adjuvant therapy for advanced prostate cancer. Med Hypotheses, 80, 617–619.
29. 29. Lowry OH, Rosenbrough NJ, Farr AL ve ark. (1951): Protein measurement with the folin-phenol reagent. J Biol Chem, 193, 265-257.
30. 30. Luna LG (1968): Manuel of histologic staining methods of Armed Forces Institute of Pathology. 1-36, McGraw-Hill Book Co, New York.
31. 31. Masuda H, Chancellor MB, Kihara K ve ark. (2006): 15- deoxy-delta12, 14-prostaglandin J2 attenuates development of cyclophoshamide-induced Cystitisin rats. Urology, 67, 435.
32. 32. Mizuoka H, Shikata N, Yang J ve ark. (1999): Biphasic effect of colchicine on acute liver injury induced by carbon tetrachloride or by dimethylnitrosamine in mice. J Hepatol, 31(5), 825-833.
33. 33. Mokhtar IY, Afrah FS (2009): Propolis protection from reproductive toxicity caused by aluminium chloride in male rats. Food Chem Toxicol, 47, 1168-1175.
34. 34. Motawi TM, Sadik NA, Refaat A (2010): Food and Chemical Toxicology. Cytoprotective effects of DL-alphalipoic acid or squalene on cyclophosphamide induced oxidative injury: An experimental study on rat myocardium, testicles and urinary bladder. Food Chem Toxicol, 48(8–9), 2326–2336.
35. 35. Mythili Y, Sudharsan PT, Selvakumar E ve ark. (2004): Protective effect of DL-α-lipoic acid on cyclophosphamide induced oxidative cardiac injury. Chem Biol Interact, 151(1), 13-19.
36. 36. Nagi MN, Al-Shabanah OA, Hafez MM ve ark. (2011): Thymoquinone supplementation attenuates cyclophosphamide-induced cardiotoxicity in rats. J Biochem Mol Toxicol, 25(3), 135-142.
37. 37. Özkocaman V (2007): Ekstramedüller toksisite: Değerlendirme, derecelendirme, prognostik faktörler. THD 2007, 22-32.
38. 38. Pascual C, Gonzales R, Torricella RG (1994): Scavenging action of propolis extract against oxygen radicals. J Ethnopharmacol, 41, 9-13.
39. 39. Pascual C, Karzai W, Meier-Helmann A ve ark. (1998): Total plasma antioxidant capacity is not always decreased in sepsis. Crit Care Med, 26, 705-709.
40. 40. Perini P, Calabrese M, Rinaldi L ve ark. (2007): The safety profile of cyclophosphamide in multiple sclerosis therapy. Expert Opin Drug Saf, 6, 183-190.
41. 41. Placer ZA, Cushman L, Johnson BC (1966): Estimation of products of lipid peroxidation in biological fluids. Anal Biochem, 16, 359-364.
42. 42. Povirk LF, Shuker DE (1994): DNA damage and mutagenesis induced by nitrogen mustards. Mutat Res Genet Toxicol, 318, 205-226
43. 43. Santos HD, Cruz WS (2001): A terapia nutritional com vitaminas, antioxidantes e o tratamento quimioterapico oncolgico. Rev Bras Cancerologia, 47, 303-308.
44. 44. Sayed-Ahmed MM, Aldelemy ML, Al-Shabanah OA ve ark. (2014): Inhibition of gene expression of carnitine palmitoyltransferase I and heart fatty acid binding protein in cyclophosphamide and ifosfamide-induced acute cardiotoxic rat models. Cardiovasc Toxicol, 14(3), 232- 242.
45. 45. Scheller S, Wilczok T, Imielski S ve ark. (1990): Free radical scavenging by ethanol extract of propolis. Int J Radiat Biol, 57(3): 461-465.
46. 46. Senkus E, Jassem J (2011): Cardiovascular effects of systemic cancer treatment. Cancer Treat Rev, 37, 300-311.
47. 47. Seven I, Aksu T, Seven PT (2012): The effects of propolis and vitamin C supplemented feed on performance, nutrient utilization and carcass characteristics in broilers exposed to lead. Livestock Sci, 148(1), 10-15.
48. 48. Shanmugarajan TS, Arunsundar M, Somasundaram I ve ark. (2008): Cardio protective effect of Ficus hispida Linn on cyclophosphamide provoked oxidative myocardial injury in a rat model. Int J Pharmacol, 1, 1-10.
49. 49. Simone CB, Simone NL, Simone V ve ark. (2007): Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 2. Altern Ther Health Med, 13(2), 40-47.
50. 50. Slordal L, Spigset O (2006): Heart failure induced by noncardiac drugs. Drug Saf, 29, 567-86.
51. 51. Souid AK, Tacka KA, Galvan KA ve ark. (2003): Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem Pharmacol, 66, 977-987.
52. 52. Sun Y, Oberly LW, Ying LA (1988): Simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497- 500.
53. 53. Swamy AV, Patel UM, Koti BC ve ark. (2013): Cardioprotective effect of Saraca indica against cyclophosphamide induced cardiotoxicity in rats: A biochemical, electrocardiographic and histopathological study. Indian J Pharmacol, 45(1), 44-48.
54. 54. Taniguchi I (2005): Clinical Significance of cyclophosphamide-induced cardiotoxicity. Intern Med, 44, 89-90.
55. 55. Toreti VC, Sato HH, Pastore GM ve ark. (2013): Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evidence-Based Complementary and Alternative Medicine Evid Based Complement Alternat Med, 2013, 1-13
56. 56. Tripathi DN, Jena GB (2009): Intervention of astaxanthin against cyclophosphamide-induced oxidative stress and DNA damage: A study in mice. Chem Biol Interact., 180, 398-406.
57. 57. Wang L, Albasi C, Faucet-Marquis V ve ark. (2009): Cyclophosphamide removal from water by nanofiltration and reverse osmosis membrane. Water Res, 43, 4115-4122.
58. 58. Yahalom J, Portlock CS (2008): Cardiac Toxicity. In:Devita VT, Hellman TS and Rosenberg‟s SA (Eds). Cancer, Philadelphia 8th edition, Chapter 63, 2678-2688.
59. 59. Yilmaz S, Kaya E, Comaklı S (2017): Vitamin E, α tocopherol, attenuates toxicity and oxidative stress induced by aflatoxin in rats. Adv Clin Exp Med, 26(6), 907-917