Determination of protective effectiveness of Nerium oleander distillation in doxorubicin-induced organ damages

Year 2014, Volume: 30 Issue: 2, 63 - 67, 01.06.2014

Burak Dik Ayşe Er Orhan Çorum

Abstract

Aim: The aim of this study was to investigate that effect of Nerium oleander (NO) distillate on doxorubicin-induced oxidative damage and other side effects. Materials and Methods: NO leaves were collected, distillated and lyophilized. In the current research, 28 rats were divided into 4 groups; Control, Doxorubicin (3 mg/kg, every other day, intraperitoneally), NO (1 mg/kg, SID, PO) and Doxorubicin (3 mg/kg, every other day, intraperitoneally) + NO (1 mg/kg, SID, PO). All treatments were performed 11 days. At 24 hours after the last administration, blood samples were taken from the hearts under general anesthetizes, and euthanized immediately. Also, heart, liver and kidney were taken and homogenized. Tissue thiobarbituric acid reactive substances (TBARS) levels, serum biochemical and hemogram values were measured by ELISA, autoanalyzer and blood cell counter, respectively. Results: Heart TBARS values of the doxorubicin group were lower (P<0.05) than Doxorubicin + NO distillate group, while kidney TBARS values of the doxorubicin group were higher (P<0.05) than the NO distillate group. Although doxorubicin decreased (P<0.05) blood cell counts, hemoglobin and hematocrit levels compared to Control group, administration of doxorubicin + NO distillate ameliorated only hematocrit levels. Doxorubicin decreased (P<0.05) serum total protein and albumin levels compared to Control group, while Doxorubicin + NO distillate increased (P<0.05) aspartate aminotransferase and blood urea nitrogen levels and decreased (P<0.05) total protein, albumin and creatinine levels.Conclusions: It may be stated that levels of NO distillate used in the current research do not prevent the doxorubicin caused side effects.

Keywords

Doxorubicin, Nerium oleander, side effect

Doksorubisinin neden olduğu organ hasarlarında Nerium oleander distilatının koruyucu etkinliğinin belirlenmesi

Abstract

Amaç: Araştırmanın amacı doksorubisinin neden olduğu oksidatif hasar ve diğer yan etkilere Nerium oleander (NO) distilatının etkisini araştırmaktır. Gereç ve Yöntem: NO yaprakları toplandıktan sonra distilasyonu yapılarak liyofilize edildi. Araştırmada 28 adet rat, Kontrol, Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama), NO (1 mg/kg/gün, oral) ve Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama) + NO (1 mg/kg/gün, oral) olmak üzere 4 gruba ayrıldı ve uygulamalar 11 gün süresince yapıldı. Son uygulamadan 24 saat sonra anestezi altındaki ratların kalplerinden kan alındı ve hemen ötenazi edildi. Ayrıca kalp, karaciğer ve böbrek organları alınarak homojenize edildi. Organ tiobarbiturik asit türevi reaktif maddeler (TBARS) düzeyleri ELISA, serum biyokimyasal değerleri otoanalizörle ve tam kan değerleri kan hücresi sayım cihazında belirlendi. Bulgular: Doksorubisin grubunun böbrek TBARS değeri NO distilatı grubundan yüksek (P

Keywords

Doksorubisin, Nerium oleander, yan etki

References

• Abdel-Raheem IT, Abdel-Ghany AA, 2009. Hesperidin alleviates doxorubicin-induced cardiotoxicity in rats. J Egypt Natl Canc Inst, 21,175-184.
• Akyol H, 2004. Kemoterapinin temel ilkeleri, XIII. TPOG Ulusal Pediatrik Kanser Kongresi, Hemşire Programı, pp: 159- 163.
• Alshabanah OA, Hafez MM, Al-Harbi MM, Hassan ZK, Al Rejaie SS, Asiri YA, Sayed-Ahmed MM, 2010. Doxorubicin toxicity can be ameliorated during antioxidant L-carnitine supplementation. Oxid Med Cell Longev, 3,428-433.
• Ayla S, Oktar H, Tanrıverdi G, Cengiz M, Ozkılıc AC, Can G, Özücer B, Eser M, Sibel Demirci S, Batur S, 2009. Doksorubisin nedenli sıçan hepatotoksisitesine nikotinaidin (koruyucu) etkisi. AÜJST, 10, 229-238.
• Barton CL, 2001. Chemotherapy, in: Small Animal Clinical Pharmacology and Therapeutics, Ed: Boothe DM, WB Saunders Company, USA, pp:330-348.
• Bas AL, Demirci S, Yazihan N, Uney K, Ermis Kaya E, 2012. Nerium oleander distillate improves fat and glucose metabolism in high-fat diet-fed streptozotocin-induced diabetic rats. Int J Endocrinol, Article ID:947187.
• Baytop T, 1984. Türkiye’de Bitkilerle Tedavi, İ. Ü. Yayınları, No: 3255, İstanbul, Türkiye, pp:411.
• Borst P, Jonkers J, Rottenberg S, 2007. What makes tumors multidrug resistant?, Cell Cycle 6, 2782-2787.
• Dik B, Sayın Z, Çorum O, 2013. Nerium oleander distilatının antimikrobiyal etkisinin araştırılması. Eurasian J Vet Sci, 29, 150-152.
• Dik B, Uney K, Ozdemir O, Demirci S, Yazıhan NA, Bas AL, 2012. Acute oral toxicity of Nerium oleander distilate in rats (Abstract). J Vet Pharmacol Therap, 35, 78-102.
• Doğan F, 2011. Veteriner hekimliğinde farmakovijilans. Eurasian J Vet Sci, 27, 19-25.
• El-Moselhy MA, El-Sheikh AA, 2014. Protective mechanisms of atorvastatin against doxorubicin-induced hepato-renal toxicity. Biomed Pharmacother, 68, 101-110.
• Hohenhaus AE, Peaston A, Maddison JE, 2002. Cancer chemotherapy, in: Small Animal Clinical Pharmacology, Eds: Maddison JE, Page SW, Church D, WB Saunders, NY, USA, pp:293-326. Hrenak J, Arendasova K, Rajkovicova R, Aziriova S, et al, 2013. Protective effect of captopril, olmesartan, melatonin and compound 21 on doxorubicin-induced nephrotoxicity in rats. Physiol Res, 62, 181-189.
• Kars MD, Gündüz U, Uney K, Baş AL, 2013. Exploring a natural MDR reversal agent: potential of medicinal food supplement Nerium oleander leaf distillate. Asian Pac J Trop Biomed, 3, 644-649.
• Kars MD, Kars G, Gunduz U, Uney K, Bas AL, 2011. Effect of Nerium oleander distillate on MCF-7 breast cancercell lines, Abstracts / Current Opinion in Biotechnology, 22, 126.
• Kav S, Hanoğlu Z, Algier L, 2008. Türkiyede kanserli hastalarda tamamlayıcı ve alternatif tedavi yöntemlerinin kullanım: Literatür taraması, UHOD, 1, 32-38.
• Kaya S, Ünsal A, 2002. İlaçların istenmeyen etkileri, in: Veteriner Hekimliğinde Farmakoloji, Eds: Kaya S, Pirinçci İ, Bilgili A, Cilt 1, üçüncü baskı, Medisan, Ankara, Türkiye, pp:142-152.
• Lorusso V, Manzione L, Silvestris N, 2007. Role of liposomal anthracyclines in breast cancer. Annals of Oncology,18,70-73. Lykkesfeldt J, 2007. Malondialdehyde as biomarker of oxidative damage to lipids caused by smoking. Clin Chim Acta, 380, 50-58.
• Ozdemir O, Ciftci MK, Maden M, 2011. Oleander poisoning in cattle. Eurasian J Vet Sci, 27, 73-76.
• Turan N, Akgün-Dar K, Kuruca SE, Kilicaslan-Ayna T, Seyhan VG, Atasever B, Meriçli F, Carin M, 2006. Cytotoxic effects of leaf, stem and root extracts of Nerium oleander on leukemia cell lines and role of the p-glycoprotein in this effect. J Exp Ther Oncol, 6, 31-38.
• Turgut K, 2000. Veteriner Klinik Laboratuar Teşhis, Bahçı- vanlar Yayınevi, Konya, Türkiye. Yazar E, Tras B, 2002.Serbest oksijen radikalleri, antioksidan enzimler ve antibiyotikler. Türk Vet Hek Derg, 14, 42-44
• Yazihan N, Bas AL, Ermis E, Demirci S, Uney K, 2013. Increased glucose uptake and insulin binding activity of Nerium oleander in hepatocytes and adipocytes. Kafkas Univ Vet Fak Derg,19, 25-30.
• Yıldırım M, Şahin E, 2008. Veteriner farmakoloji ve toksikolojide transport proteinleri. İstanbul Üniv Vet Fak Derg, 34, 9-17.
• Zolfagharzadeh F, Roshan VD, 2013. Pretreatment hepatoprotective effect of regular aerobic training against hepatic toxicity induced by doxorubicin in rats. Asian Pac J Cancer Prev, 14, 2931-2936.