Effect of Disulphide Derivative of Dihydroartemisinin on the Haematological Indices of N-Methyl-N-Nitrosourea Injected Rats.
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Dihydroartemisinin (DHA) possesses anticancer activity but limited by its short half-life. Recently, a novel cancer chemotherapeutic agent, a disulphide derivative of DHA (sDHA) has been synthesized with the aim of extending its half-life. N-methyl-N-nitrosourea (MNU) has been largely used to induce cancer in the study of a variety of novel cancer chemotherapeutic agents. MNU induced carcinogenesis causes alterations in haematological parameters. This study evaluates the effect of sDHA on the haematological indices of MNU injected rats. MNU (50 mg/kg) was administered intravenously as single dose to different animal groups (n=10), followed ten days later by oral treatment with sDHA (37.42, 74.83 and 112.25 mg/kg), Tween 80 (0.3 ml) and distilled water (0.3 ml) once daily for 28 days. Animals were observed for 52 days after drug treatments after which the animals were sacrificed and blood collected for assay of haematological parameters [Hb, RBC, PCV, MCH, MCHC, PLT, WBC and WBC differentials (eosinophils, neutrophils, lymphocytes, monocytes and basophils)]. MNU significantly (p<0.0001) increased serum levels of WBC and differentials and decreased the levels of all red blood indices studied. Oral treatment with sDHA resulted in significant (p<0.001) dose-dependent reductions in the serum levels of MNU-induced elevations of WBC and differentials and increased MNU-induced reduction of PCV and PLT levels in a dose-dependent manner, and that of RBC, Hb, MCH and MCHC at the highest dose administered (112.25mg/kg). The study shows that sDHA has the potential to ameliorate the MNU-induced alterations in haematological indices in rats.
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Références
Ali.S. (2014). Questions and guide to answers (Q&A) in internal medicine: give an account on compartment syndrome, hyperhomocysteinemia, brain natriuretic peptide, and viral autoimmune manifestations. Egypt Journal of Internal Medicine; 26:186-92
Ashton, M., Sy N.D., Huong, N.V., Gord,i T., Hai, T.N., Huong, D.X., Niêu, N.T. and Cng, LD. (1998). Artemisinin kinetics and dynamics during oral and rectal treatment of uncomplicated malaria. Clinical Pharmacology and therapeutics 63(4):482-493
Bassey, U.B. (2015). Synthesis, characteristics and antimalarial study of the deoxy and disulphide derivatives of dihydroartemisinin. M.Sc Thesis, Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Nigeria. Supervisor: Prof. E.E. Essien.
Golding, B, T., Bleasdale, C., Mcginnis, J., Watson, W. P.(1997). The mechanism of decomposition of N-methyl- N-nitrosourea (MNU) in water and a study of its reactions with 2?-deoxyguanosine, 2?-deoxyguanosine 5?-monophosphate and d(GTGCAC). Tetrahedron 53(11):4063-4082.
Iqbal, M., Younis, M., Shoukat, N., Shaikh, S, Akram, N., Abbas, R., Shahzad, K. A., Mazhar, K, Rehman, F. (2015). Hematological study of cancer patients with radio-chemotherapy. Science letters3(2):75-79.
Jiao, Y., Ge, C.M., Meng, H.G., Cao, J.P., Tong, J., Fan, S.J. (2007).Dihydroartemisinin is an inhibitor of ovarian cancer cell growth. Acta Pharmacol Sin; 28(7):1045–56.
Li, Y. (2012).Qinghaosu (artemisinin): Chemistry and pharmacology. Acta Pharmacol Sin; 33(9):1141–6.
Macejova’, D. and Brtko, J. (2001). Chemically induced carcinogenesis: A comparison of 1-Methyl-1-Nitrosourea, 7, 12-dimethylbenzanthracene, diethylnitroso-amine and azoxymethane models.(Minireview). Endocrine regulations. vol. 35, 53-59
Mani, S., Ram, B.R., Kuldeep, D., Babu, L.J., Subramaniyam, S., Gopikunte,J.R., Inbaraj, S., Kuppusamy, K., Singaram,B. and Arumugam, G. (2014). Effect of Morinda citrifolia(Noni) Fruit Juice on Antioxidant, Haematoloical and Biochemical Parameters in N-Methyl-N-Nitrosourea (NMU) induced Mammary carcinogenesis in Sprague-Dawley Rats. International Journal of Pharmacology: 10(2):109-119.
Meyer, J.E., Cohen S.J. (2011). Beyond first-line therapy: Combining chemotherapy and radioembolization for hepatic colorectal metastases. Journal of Nuclear Medical Radiation Therapy; 2:103.
Muriithi, N.J., Maina, G. S., Mugendi, N.M., Maina, M.B., Kiambi, M.J., Kelvin, J.K., Aliyu, U. A., John, M.K., Ann, N.W., Abdirahman, Y.A., Ngugi, M. P. and Eliud, N.M. (2015). Determination of Hematological Effects of Methanolic Leaf Extract of S. incanum in Normal Mice. Pharm Anal Acta; 6(10):429-435
Ochei, J., and Kolhatkar, A. (2008). Complete blood count: In Medical Laboratory Science Theory and Practice. 7th Edition Tata McGrawHill, pp 273 –277.
Parikh, R.R., Gildener-Leapman, N., Narendran, A., Lin, H., Lemanski, N., Bennett, J.A, (2005). Prevention of N-Methyl-N-Nitrosourea-Induced Breast Cancer by a-Fetoprotein (AFP)-Derived Peptide, a Peptide Derived from the Active Site of AFP. Clinical Cancer Research; 11:8512-20.
Rajkhowa, S., Hussain, I., Hazarika, K.K.,Sarmah, P., Deka, R.C. (2013). Quantitative structure-activity relationships of the antimalarial agent artemisinin and some of its derivatives - a DFT approach. Comb Chem High Throughput Screen; 16(8):590-602.
Rodrigues, B., McNeill, J.H. (1992). The diabetic heart: metabolic causes for the development of cardiomyopathy. Cardiovascular Research 26: 913-922
Tarun, V., Yash, P., Diksha, J.(2014). An updated review on cancer.International Journal of Pharmacological Research; 4(2):91-102.
Tsubura, A., lai, Y., Miki, H., Sasaki, T., Uehara, N., Yuri,T. and Yoshizawa, K. (2011). Review: Animal Models of N-Methyl-N-nitrosourea-induced Mammary Cancer and Retinal Degeneration with Special Emphasis on Therapeutic Trials. in vivo25: 11-22
Varlotto, J., Stevenson, M.A.(2005). Anemia, tumor hypoxemia and the cancer patient. Int J RadiatOncolBiolPhys;. 63: 25-36. 3.
CCAC- Canadian Council On Animal Care. The Care and Use of Farm Animals in Research, Teaching and Testing. 12-15. Ottawa; 2009.