Siklofosfamid Nedenli Hematoksisite Üzerine Karvakrolün Sitoprotektif Etkileri

Öz

Siklofosfamid (SP) klinikte kanser ve malign olmayan hastalıkların tedavisinde yaygın olarak kullanılan alkilleyici sitotoksik bir ilaçtır. Ancak yüksek doz SP, kan ve kemik iliğinde toksisiteye neden olmaktadır. Bu çalışma, deneysel olarak oluşturulmuş hematoksisitede uçucu yağların temel bileşeni olan ve antioksidan özellikleri bilinen karvakrol (KAR)’ün kan ve kemik iliğinde olası koruyucu etkilerini saptamak amacıyla yapılmıştır. Çalışma, Sprague-Dawley cinsi 63 adet erkek sıçan, her grupta 7 hayvan olacak şekilde 9 gruba ayrılmıştır. Anestezi altında intrakardiyak kan alımı yapıldıktan sonra sıçanların femurundan kemik iliği çıkarılmıştır. İntraperitonal (i.p.) SP uygulaması doz artışına paralel olarak sırasıyla lökosit (% 77, % 86), trombosit (% 30, % 35) ve kemik iliği çekirdekli hücre sayılarını (% 82, % 94) azalttı. Siklofosfamid ile birlikte 5 ve 10 mg kg-1 KAR verilen deney gruplarındaki lökosit, trombosit ve kemik iliği çekirdekli hücre sayılarının sadece SP verilen gruplara göre önemli bir oranda arttığı görülmüştür (p<0.001). Siklofosfamid nedenli myelosupresyon ve hematoksisitenin önlenmesinde 10 mg kg-1 KAR, 5 mg kg-1 karvakrole göre daha koruyucu olmuştur. Veriler, KAR dozunun belirli oranlarda değiştirilmesiyle, artan SP dozuna karşı daha güçlü bir koruyucu etkinliğin sağlanabileceğini düşündürmektedir.

Anahtar Kelimeler

• Siklofosfamid,hematoksisite,karvakrol,hücre koruyucu

Cytoprotective Effects of Carvacrol on Cyclophosphamide Induced Hematoxicity

Öz

Cyclophosphamide (CP) is an alkylating cytotoxic drug commonly used clinically for the treatment of cancer and non-malignant diseases. However, high doses of CP causes blood and bone marrow toxicity. This study was conducted to investigate the possible protective effects of carvacrol (CAR), which is the basic component of essential oils and has antioxidant properties, in blood and bone marrow in experimental hematoxicity. In the study, 63 male Sprague-Dawley rats were divided into 9 groups as 7 animals in each group. After receiving intracardiac blood from animals under anesthesia, the bone marrow from the femur of the rats was carefully removed. Intraperitoneal (i.p.) CP administration reduced leukocyte (77%, 86%), thrombocyte (30%, 35%) and bone marrow nucleated cell counts (82%, 94%), respectively, parallel to the dose increase. Leukocyte, thrombocyte and bone marrow nucleated cell counts in CP and 5 and 10 mg kg-1 CAR administered groups was significantly increased (p<0.001) compared to the CP alone. In the prevention of CP-induced myelosuppression and hematoxicity, 10 mg kg-1 CAR was more protective than 5 mg kg-1 CAR. The data suggest that by modifying the CAR dose at certain ratios, a stronger protective effect against the increased CP dose can be achieved.

Anahtar Kelimeler

• Cyclophosphamide,hematoxicity,carvacrol,cell protective

Kaynakça

1. Aechbach, R., Löliger, J., Scott, B.C., Murcia, A., Butler, J., Halliwell, B., Aruoma, O.I., 1994. Antioxidant actions of thymol, carvacrol, 6-gingerol, zingerone and hydroxy tyrosol. Food Chemical Toxicology, 32(1): 31-36.
2. Ayhanci, A., Uyar, R., Aral, E., Kabadere, S., Appak, S., 2008. Protective effect of zinc on cyclophosphamide-induced hematoxicity and urotoxicity. Biological Trace Element Research, 126(3): 186-193.
3. Ehrenfried, J.A., Ko, T.C., Thompson, E.A., Evers, B.M., 1997. Cell cycle-mediated regulation of hepatic regeneration. Surgery, 122(5): 927-935.
4. Fairchild, W.V., Spencer, C.R., Solomon, H.D., Gangai, M.P., 1979. The incidence of bladder cancer after cyclophosphamide therapy. Journal of Urology, 122(2): 163-164.
5. İpek, E., Zeytinoğlu, H., Okay, S., Tüylü, B.A., Kürkcüoğlu, M., Başer, K.H.C., 2005. Genotoxicity and antigenotoxicity of origanum oil and carvacrol evaluated by ames Salmanella/microsomal test. Food Chemistry, 93(3): 551-556.
6. Kalaycıoğlu, M.E., Lichtin, A.E., Andrese, S.W., Tuason, L., Bolwell, B.J., 1995. High-dose busulfan and cyclophosphamide followed by autologous bone morrow transplantation and/or peripheral blood progenitor cell rescue for metastatic breast cancer. American Journal of Clinical Oncolology, 18(6): 491-494.
7. Kawabata, T.T., Chapman, M.Y., Kim, D.H., Stevens, W.D., Holsapple, M.P., 1990. Mechanism of in vitro immunusuppression by hepatocyte generated cyclophosphamide metabolites and 4-hydroxi cyclophosphamide. Biochemical Pharmacology, 40(5): 927-935.
8. Kayaalp, S.O., 1989. Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. Feryal Matbaacılık, Ankara.

9. Kumar, K.B.H., Kuttan, R., 2004. Chemoprotective activity of an extract of phyllanthus amarus against cyclophosphamide-induced toxicity in Mice. Phytomedicine, 12(6-7): 494-500.
10. Moore, F.R., Urda, G.A., Krishna, G., Theiss, J.C., 1995. An invivo/invitro method for assessing micronucleus and chromosome aberration induction in rat bone morrow and spleen. 1. Studies with cyclophosphamide. Mutation Research/Environmental Mutagenesis and Related Subjects, 335(2): 191-199.
11. Pool, B.L., Bos, R.P., Niemeyer, U., Theuws, J.L.G., Schmalhl, D., 1988. Invitro/invivo effect of mesna on the genotoxicity and toxicity of cyclophosphamide a study aimed at clarifying theultmechanim of mesna’s anticarsinogenic activity. Toxicology Letters, 41: 49-56.
12. Sanz, N., Fernandez, C.D., Simon, L.F., Alvarez, A.,Cascales, M., 1998. Necrogenic and regeneratives responses of liver of newly weaned rats against a sublethal dose of thioacetamide. Biochimica et Biophysica Acta, 1384(1): 66-78.
13. Senthilkumar, S., Devaki, T., Manohar, B.M., Babu, M.S., 2006. Effect of squalene on cyclophosphamide-induced toxicity. Clinica Chimitica Acta, 364(1-2): 335-42.
14. Tran, T., Casabianca, H., Loustalot, M.F.G., 2006. Deuterium/hydrogen ratio analysis of thymol, carvacrol, gamma-terpinene and p-cymene in thyme, savory and oregano essential oils by gas chromatography-pyrolysis-isotoperatio mass spectrometry. Journal of Chromatography A, 1132(1-2): 219-27.
15. Trasler, J.M., Hales, B.F., Robaire, B., 1987. A time- course study of chronic paternal cyclophosphamide treatment in rats: Effects on pregnancy outcome and the male reproductive and hematologic systems. Biology of Reproduction, 37(2): 317-326.
16. Uyar, R., Bayçu, C., Gürer, F., Erol, K., Cingi, M.Ġ., Özdemir, M., Alpan, R.S., 1990. Metotreksat’ın kemik iliğindeki toksisitesini verapamil ile azaltılabilir mi? Osmangazi Tıp Dergisi, 18(1): 29- 39.
17. Yeşildağ, O., 2012. Siklofosfamid nedenli hematoksisite üzerine karvakrol’ün sitoprotektif etkileri. Yüksek lisans tezi, Eskişehir Osmangazi Üniversitesi, Fen Bilimleri Enstitüsü, Eskişehir.