Investigation into the Protective Effects of Escin on Blood Cells and Cyclophosphamide-Induced Bone Marrow Toxicity in Rats

Abstract

Cyclophosphamide (CPM) is an extensively used antineoplastic drug that induces toxicity in the health cell because of its metabolites. The main disadvantage of this drug is myelosuppression. Escin (ES) is a natural mixture of triterpenoid saponins that has biological properties such as antioxidant, anti-inflammation, and anti-edematous. The present study aims to investigate the possible effects of ES upon the toxic effects of CPM on blood cells and bone marrow. Spraque Dawley male rats were chosen and categorized into 4 different groups, including the control group, 200 mg/kg CPM, 10 mg/kg ES and ES+CPM. Rats in all groups were discontinued 1 day after injections. After the animals were cut under anesthesia, bone marrow and blood samples were collected. A fall in the number of erythrocyte, hemoglobin, hematocrit, leukocyte (97%), platelets (45%), and bone marrow cells (93.6%) was seen in the CPM group. Conversely, blood cells (erythrocyte, hemoglobin, hematocrit, leukocyte, and platelets), as well as bone marrow cells in ES + CPM had increased by comparison with CPM. Our results show that treating rats with a selected dose range of ES may help decrease the toxic effects of CPM upon blood cells and bone marrow.

Keywords

• Escin
• Cytoprotective
• Cyclophosphamide
• Hematotoxicity
• Rats

Siklofosfamid Nedenli Kan Hücreleri ve Kemik İliği Toksisitesi Üzerine Escinin Koruyucu Etkilerinin Sıçanlarda Araştırılması

Abstract

Siklofosfamid (CPM), metabolitleri nedeniyle kanserli hücrelerin yanı sıra sağlıklı dokularda da toksisiteye neden olan yaygın olarak kullanılan bir antineoplastik ilaçtır. Bu ilacın ana dezavantajı miyelosupresyondur. Escin (ES), antioksidan, antienflamasyon ve anti-ödem gibi biyolojik özelliklere sahip doğal bir triterpenoid saponin karışımıdır. Bu çalışma, CPM'nin kan hücreleri ve kemik iliği üzerindeki toksik etkileri üzerine ES’nin olası etkilerini araştırmayı amaçlamaktadır. Spraque Dawley erkek sıçanlar, kontrol grubu, 200 mg / kg CPM, 10 mg / kg ES ve CPM+ES olmak üzere 4 farklı gruba ayrıldı. Tüm gruplardaki sıçanlar enjeksiyonlardan 1 gün sonra kesildi. Hayvanlar anestezi altında kesildikten sonra kemik iliği ve kan örnekleri alındı. CPM grubunda eritrosit, hemoglobin, hematokrit, lökosit (% 97), trombositler (% 45) ve kemik iliği hücreleri (% 93.6) sayısında kontrol grubuna göre bir azalma vardı. Tersine, ES + CPM' grubundaki kan hücreleri (eritrosit, hemoglobin, hematokrit, lökosit ve trombositler) ve kemik iliği hücreleri CPM verilen grup ile karşılaştırıldığında artmıştır. Sonuçlarımız, ES ile sıçanların tedavi edilmesinin, CPM'nin kan hücreleri ve kemik iliği üzerindeki toksik etkilerini azaltmaya yardımcı olabileceğini göstermektedir.

Keywords

• Escin
• Sitoprotektif
• Siklofosfamid
• Hematotoksisite
• Sıçan

References

1. Ayhanci, A., Heybeli, N., Sahin, İ. K., Cengiz, M. Myelosuppression and Oxidative Stress Induced by Cyclophosphamide in Rats: The Protective Role of Selenium. Adıyaman Üniversitesi Fen Bilimleri Dergisi, 9(2), 252-265.
2. Kumari, J., Shaoo, P. K. (2005). Effects of cyclophosphamide on the immune system and disease resistance of Asian catfish Clarias batrachus. Fish Shellfish Immunolology, 19: 307–316..
3. Shah, A. S., Wakade, A. S., Juvekar, A. R. (2008). Immunomodulatory activity of methanolic extract of Murraya koenigii (L) Spreng leaves. Ind J Exp Biolology, 46 (7): 505–509.
4. George, K. S., Rajesh, R., Sunil Kumar, S., Sulekha, B., Balaram, P. (2008). A polyherbal ayurvedic drug Indukantha Ghritham as an adjuvant to cancer chemotherapy via immunomodulation. Immunobiology, 213:641–649
5. Langford, C. A. (1997). Complications of cyclophosphamide therapy. Eur Arch Otorhinolaringol, 254:65–72.
6. Manda, K., & Bhatia, A. L. (2003). Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice. Cell Biol. Toxicolology, 19:367–372.
7. Kumar, K. B. H., Kuttan, R. (2005) Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice. Phytomedicine, 12:494–500.
8. Fu, F., Hou, Y., Jiang, W., Wang, R., Liu, K. (2005). Escin: inhibiting inflammation and promoting gastrointestinal transit to attenuate formation of postoperative adhesions. World J. Surg,. 29, 1614–1620.

9. Sirtori, C.R. (2001). Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol. Res,. 44, 183–193.
10. Cengiz, M., Kutlu, H. M., Peker Cengiz, B., Ayhancı, A. (2020). Escin attenuates oxidative damage, apoptosis and lipid peroxidation in a model of cyclophosphamide-induced liver damage. Drug and Chemical Toxicology, 1-8.
11. Cengiz, M., Yeşildağ, Ö., Ayhanci, A. (2018). Siklofosfamid Nedenli Hematoksisite Üzerine Karvakrolün Sitoprotektif Etkileri. Türkiye Tarımsal Araştırmalar Dergisi, 5(2), 125-130.
12. Liang, J., Huang, M., Duan, W., Yu, X. Q., Zhou, S. (2007). Design of new oxazaphosphorine anticancer drugs. Curr Pharm Design, 13:963– 978.
13. George, K. S., Rajesh, R., Sunil-Kumar, S., Sulekha, B., Balaram, P. (2008). A polyherbal ayurvedic drug—Indukantha Ghritham as an adjuvant to cancer chemotherapy via immunomodulation. Immunobiology, 213:641–649.
14. Ayhanci, A., Yaman, S., Appak, S., Gunes, S. (2009). Hematoprotective effect of seleno-L-methionine on cyclophosphamide toxicity in rats. Drug and Chemical Toxicology, 32:4, 424-428.
15. Fraiser, L. H., Kanekal, S., Kehrer, J. P. (1991) Cyclophosphamide toxicity: characterizing and avoiding the problem. Drugs, 42:781–795.
16. Schuurman, H. J., Smith, H. T., Cozzi, E. (2005). Tolerability of cyclophosphamide and methotrexate induction immunosuppression in nonhuman primates. Toxicology, 213:1–12.
17. Moore, F. R., Urda, G. A., Krıshna, G., Theıss, 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.
18. Cengiz, M. (2018). Hematoprotective effect of boron on cyclophosphamide toxicity in rats. Cell Mol. Biol., (Noisy le Grand). 64 (5) 62-65.
19. 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 themalere productive and hematologic systems. Biology of Reproduction, 37(2):317-26.
20. Hu, X.M., Zeng, F.D. (2004). Protective effects of sodium beta-aescin on ischemia reperfusion injury in rat brain. Acta Pharm. Sin., 39 (6), 419–423.
21. Jiang, N., Xin, W., Wang, T. et al. (2011). Protective effect of aescin from the seeds of Aesculus hippocastanum on liver injury induced by endotoxin in mice. Phytomedicine, 18(14), 1276–1284.