PROTECTIVE EFFECTS OF Β-GLUCAN AND G-CSF ON THE PHYSIOLOGICAL ALTERATIONS INDUCED BY CYCLOPHOSPHAMIDE IN MICE

Authors

  • Dr. Idriss H. Mohamed Zoology Department, Faculty of Science, Omar AL-Mukhtar University, Albida.

DOI:

https://doi.org/10.53555/eijas.v1i3.16

Keywords:

Cyclophosphamide, G-CSF, β-glucan, antioxidants, hepatocytes

Abstract

Cyclophosphamide (CTX) is a DNA alkylating chemotherapeutic agent, causing hepatocytes injury. Granulocyte colony stimulating factor (G-CSF) promotes granulocyte counts and antioxidants to increase. This study aimed to investigate the effect of certain natural products such as β- glucan from medicinal fungi as adjuvant systems to reduce toxicity of chemotherapy, enhance the effects of G-CSF to mobilize stem cells and improve the quality of hepatocytes functions. Naïve mice were injected with CTX, G-CSF and β-glucan for five days then physiological parameters were measured. The results showed that CTX administration decreased the parameters of red blood cell distribution width (RDW) counts and total white blood cells)WBC( count. Furthermore, CTX administration has hepatocyte oxidative stresseffectwhich is characterized by increasing prooxidants xanthine oxidase (OX), thiobarbituric acid-reactive substances (TBARS) and decreasing of antioxidants glutathione peroxidase (GPx).As a result, hepatocytes injury, characterized by elevating of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities occurred. The treatment of mice with G-CSF and β-glucansuccess fully normalized the physiological parameters by returning WBCs, RDW and lymphocytes counts to normal levels, hepatocytes oxidative stress characterized by decreasing Prooxidants OX,TBARS and increasing antioxidants GPx reflected by significant decrease in the serum activities of AST and ALT activities.

References

. Ahmed AR, Hombal SM.Cycophosphamide (Cytoxan). A review on relevantpharmacology and clinical uses (1984). J Am Acad Dematol, 11:1115-26.

. Moore MJ. Clinical pharmacokinetics of cyclophosphamide (1991). Clin Pharmacokinet, 20:194-208.

. Khan TS, Sundin A, Juhlin C, Wilander E, Oberg K, Eriksson B. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment ofrecurrent or metastatic adrenocortical cancer (2004). Med Oncol, 21:167-7.

. Huang Z, Raychowdhury MK, Waxman DJ. Impact of liver P450 reductasesuppression on cyclophosphamide activation, pharmacokinetics and antitumoralactivity in cytochrome P450-based cancer gene therapy model (2000). Cancer GeneTher, 7:1034-42.

. Salem, M. L.; Al-Khami, A. A.; El-Nagaar, S. A.; Zidan, A. A.; Al-Sharkawi, I. M.; Marcela Diaz-Montero, C. and Cole, D. J. (2012): Kinetics of rebounding of lymphoid and myeloid cells in mouse peripheral blood, spleen and bone marrow after treatment with cyclophosphamide. Cell Immunol, 276: 67-74.

. Colvin, O. M. (1999): An overview of cyclophosphamide development and clinical applications. Curr Pharm Des, 5: 555-560.

. Zhu L, Yin Y, Xing J, et al. (2009). Therapeutic efficacy of Bifidobacterium longummediated human granulocyte colony-stimulating factor and/or endostatin combined with cyclophosphamide in mouse-transplanted tumors. Cancer Sci. 100(10):19861990.

. Feldman, B.F., J.G., Zinkl and N.C. Jain, (2000). Schalm’s Veterinary Hematology. 1st Edn. Wiley, Ames, ISBN-10: 0683306928, pp: 1344.

. Burits, C.A., and E.R., Ashwood, (3rd Ed), 1999.Tietz text book of clinical chemistry. Philadelphia, WB Saunders, pp: 1840-1845.

. P. R., Kind, and E. J., King, (1954) “Estimation of plasma phosphates by determination of hydrolyzed phenol with antipyrin,” Jof ClinPath. 7: 322–326.

. Tappel, L. and Zalkin, H., (1959).Inhibition oflipid peroxidation in mitochondria by vitamin E. J of Arch Biochem and Bio. 80: 333-336.

. Litwack, G., Bothwell, J. W., Williams, J. N., Jr., and Elvehjem, C. A., (1953).A colorimetric assay for xanthine oxidase in rat liver homogenates.The Jof Biolo Chem. 200: 303-310.

. Paglia, D. E., and Valentine, W. N., (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. The J of Labor and Clin Med.70: 158-169.

. Drury, R. And Wallington, 1986.CarltonsHistologicalTechnique. 4th Edn. Oxford University Press,

N.Y,.Toronto.

. Huyan, X. H.; Lin, Y. P.; GAO, T.; Chen, R. Y. and Fan, Y. M. (2011): Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb/c mice. Int Immunopharmacol, 11: 1293-1297.

. Liu, F.; Wu, H. Y.; Wesselschmidt, R.; Kornaga, T. and Link, D. C. (1996): Impaired production and increased apoptosis of neutrophils in granulocyte colonystimulating factor receptor-deficient mice. Immunity, 5: 491-501.

. Demetri, G. D. and Griffin, J. D. (1991): Granulocyte colony-stimulating factor and its receptor. Blood, 78: 2791-2808.

. Mathew, S. and Kuttan, G. (1997): Antioxidant activity of Tinospora cordifolia and its usefulness in the amelioration of cyclophosphamide induced toxicity. J Exp Clin Cancer Res, 16: 407-411.

. Premkumar, K.; Pachiappan, A.; Abraham, S. K.; Santhiya, S. T.; Gopinath, P. M. and Ramesh, A. (2001): Effect of Spirulina fusiformis on cyclophosphamide and mitomycin-C induced genotoxicity and oxidative stress in mice. Fitoterapia, 72: 906911.

. Soni S, Shrivastava V. Carbendazim induced histopathological changes and some enzyme activities (GOT, GPT, ACP and ALP) in liver and kidneys of male Rattus rattus.Int J Pharm Sci Health Care. 2013; 5(3):19-35.

. Davila, J. C.; Lenherr, A. and Acosta, D. (1989): Protective effect of flavonoids on drug-induced hepatotoxicity in vitro. Toxicology, 57: 267-286.

. Arayne, M. S.; Sultana, N. and Bahadur, S. S. (2007): The berberis story: Berberis vulgaris in therapeutics. Pak J Pharm Sci, 20: 83-92.

Downloads

Published

2015-09-27