Role of 5-Fluorouracil Chitosan Nanoparticles on Decreasing the Oxidative Stress in Mice Bearing Ehrlich Carcinoma
DOI:
https://doi.org/10.21608/jntas.2020.36757.1025Keywords:
5-fluorouracil chitosan nanoparticles (5FUCNPs), Ehrlich carcinoma, angiogenic markersAbstract
5-Fluorouracil (5-FU) as anticancer drug has many side effects. Site-specific delivery of 5-FU would reduce the systemic side effects and provide effective and safe therapy. Chitosan nanoparticles (CNPs) are used in drug delivery systems. In the present study the effects of 5-fluorouracil chitosan nanoparticles (5FUCNPs) on decreasing the oxidative stress were investigating within a model of female mice bearing solid Ehrlich carcinoma (EC). 7 days After solid tumor induction, 5-FUCNPs were administrated by gavages (0.5 mg/kg body weight) to mice for 15 days. Tumor size was monitored; oxidative stress markers were assessed. In addition, the angiogenic markers concentrations were evaluated. In vitro, 5FUCNPs showed high cytotoxic effect on EC tumor cells. Gavages of EC-bearing mice with 5FUCNPs significantly reduced tumor size, increased MDA level, decreased GSH level and recorded great destruction in tumor tissues. Meanwhile, in liver tissue MDA level significantly decreased and GSH level increased. On the other hand, a significant decrease in the levels of angiogenic markers were recorded. In conclusion: CNPs as a drug carrier for 5-FU have a role in reducing tumor growth and may represent a novel class of anticancer drug.
References
Abbasalipourkabir, R.; Salehzadeh, A. and Abdullah, R. (2011): Cytotoxicity Effect of Solid Lipid Nanoparticles on Human Breast Cancer Cell Lines. Biotechnology; 10: 528.
Agrawal, S.S.; Saraswati, S.; Mathur, R. and Pandey, M. (2011): Cytotoxic and antitumor effects of brucine on Ehrlich ascites tumour and human cancer cell line. Life Sci.; 89: 147.
Ahmed, M.I.; Salahy, E.E.; Fayed, S.T.; El-Hefnawy, N.G. and Khalifa, A. (2001): Human papillomavirus infection among Egyptian females with cervical carcinoma: relationship to spontaneous apoptosis and TNF-alpha. Clin. Biochem.; 34(6): 491.
Alvarez-Lorenzo, C.; Sosnik, A. and Concheiro, A. (2011): PEO-PPO block copolymers for passive micellar targeting and overcoming multidrug resistance in cancer therapy. Curr. Drug Targets; 12: 1112.
Banerjee, T.; Mitra, S.; Singh, A.K.; Sharma, R.K. and Maitra, A.N. (2002): Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles. Int. J. Pharm.; 243(1–2): 93.
Beutler, E.; Duron, O. and Kelly, B.M. (1963): Improved method for the determination of blood glutathione. J. Lab. Clin. Med.; 61: 882.
Burns, E.R. and Beland, S.S. (1983): Induction by 5-fluorouracil of major phase difference in the circadian profiles of DNA synthesis between the Ehrlich ascites carcinoma and five normal organs. Cancer Lett.; 20: 235.
Dor, Y.; Porat, R. and Keshet, E. (2001): Vascular endothelial growth factor and vascular adjustments to perturbations in oxygen homeostasis. Am. J. Physiol. Cell Physiol.; 280: 1367.
Driscoll, K.E. (2000): TNF-alpha and MIP-2: Role in particle-induced inflammation and regulation by oxidative stress. Toxicol. Lett.; 112–113: 177.
El-Merzabani, M.M.; El-Aaser, A.A.; Attia, M.A.; El-Duweini, A.K. and Ghazal, A.M. (1979): Screening system for Egyptian plants with potential anti-tumour activity. Planta Med.; 36: 150.
Estanqueiro, M.; Amaral, M.H.; Conceição, J. and Lobo, J.M.S. (2015): Nanotechnological carriers for cancer chemotherapy: The state of the art. Colloids Surf. B; 126: 631.
Feghali, C.A. and Wright, T.M. (1997): Cytokines in acute and chronic inflammation. Front. Biosci.; 2: d12.
Fen, W.; Feng, G.; Minbo, L.; Huihui, Y.; Yongping, H. and Jianwen, L. (2009): Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells. Toxicol. In Vitro; 23: 808.
Fubini, B. and Hubbard, A. (2003): Reactive oxygen species and reactive nitrogen species generation by silica in inflammation and fibrosis. Free Radic. Biol. Med.; 34: 1507.
Ghoneum, M.; Badr El-Din, N.K.; Noaman, E. and Tolentino, L. (2008): Saccharomyces cerevisiae, the Baker’s Yeast, suppresses the growth of Ehrlich carcinoma-bearing mice. Cancer Immunol. Immunother.; 57: 581.
Hu, Y.; Jiang, X.; Ding, Y.; Ge, H.; Yuan, Y. and Changzheng, Y. (2002): Synthesis and characterization of chitosan-poly(acrylic acid) nanoparticles. Biomaterials; 23: 3193.
Kerbel, R.S. (2008): Tumor angiogenesis. The New England J. of Med.; 358(19): 2039.
Mitra, S.; Gaur, U.; Ghosh, P.C. and Maitra, A.N. (2001): Tumor targeted delivery of encapsulated dextran–doxorubicin conjugate using chitosan nanoparticles as carrier. J. Control. Release; 74(1–3): 317.
Okuda, M.; Li, K.; Beard, M.R.; Showalter, L.A.; Scholle, F.; Lemon, S.M. and Weinman, S.A. (2002): Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology; 122(2): 366.
Ozaslan, M.; Karagoz, I.D.; Kilic, I.H. and Guldur, M.E. (2011): Ehrlich ascites carcinoma. Afr. J. Biotechnol.; 10(13): 2375.
Peters, K.; Unger, R.E.; Gatti, A.M.; Sabbioni, E.; Tsaryk, R. and Kirkpatrick, C.J. (2007): Metallic nanoparticles exhibit paradoxical effects on oxidative stress and proinflammatory response in endothelial cells in vitro. Int. J. Immunopathol. Pharmacol.; 20: 685.
Qi, L.; Xu, Z.; Li, Y.; Jiang, X. and Han, X. (2005): In vitro effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 cells. World J. Gastroenterol.; 11(33): 5136.
Ravi Kumar, M.N.V. (2000): A review of chitin and chitosan applications. React. Funct. Polym.; 46: 1.
Savita, B. and Amarnath, M. (2009): Dextran–doxorubicin/chitosan nanoparticles for solid tumor therapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.; 1(4): 415.
Thanoo, B.C.; Sunny, M.C. and Jayakrishnan, A. (1992): Cross-linked chitosan microspheres: Preparation and evaluation as a matrix for the controlled release of pharmaceuticals. J. Pharm. Pharmacol.; 44: 283.
Wang, X.; Wang, Y.; Chen, Z. and Shin, D. (2009): Advances of cancer therapy by nanotechnology. Cancer Res. Treat.; 41(1): 1.
Wettergren, Y.; Carlsson, G.; Odin, E. and Gustavsson, B. (2012): Pretherapeutic uracil and dihydrouracil levels of colorectal cancer patients are associated with sex and toxic side effects during adjuvant 5-fluorouracil-based chemotherapy. Cancer; 118: 2935.
Yang, H.C. and Hon, M.H. (2009): The effect of the molecular weight of chitosan nanoparticles and its application on drug delivery. Microchem. J.; 92(1): 87.
Yoshioka, T.; Kawada, K.; Shimada, T. and Mouri, M. (1979): Lipid peroxidation in maternal and cord blood and protective mechanism against activated oxygen toxicity in the blood. Am. J. Obstet. Gynecol.; 135: 372.
Zhang, D.Y.; Shen, X.Z.; Wang, J.Y.; Dong, L.; Zheng, Y.L. and Wu, L.L. (2008): Preparation of chitosan-poly(aspartic acid)-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice. World J. Gastroenterol.; 14: 3554.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
