Cytoprotectivity of the natural honey against the toxic effects of Doxorubicin in mice
Affiliation(s)
Department of Biology, Faculty of Science, University of King Abdulaziz, Jeddah, KSA. Department of Biology, Faculty of Science, University of Kerkuk, Kerkuk, Iraq.
Department of Biology, Faculty of Science, University of King Abdulaziz, Jeddah, KSA. Department of Biology, Faculty of Science, University of Kerkuk, Kerkuk, Iraq.
ABSTRACT
The protectivity of the natural honey has been assessed against the toxicity of Doxorubicin (DOX) in liver tissues of 106 male Albino mice Mus musculus strain weighing 37 ± 3 gm. The body and liver weights, morphological behavior changes, liver function and pathological effects on liver were recorded. Toxicity study of DOX showed that the LD50 and LD were 20 and 30 mg/Kg, respectively. Intra-peritoneal (i.p.) injection of DOX induced significant (p ≤ 0.01-0.001) pathological changes in the health, i.e. general weakness, a few morphological changes associated with bleedings, ulceration of skin, hair loss, dimorphism of limbs and bosselation. Daily ingestion of natural honey for seven weeks has led to significant (p ≤ 0.01-0.001) improvement of these symptoms which appeared as increases in both body and liver weights in comparison with control animals. The natural honey had enhanced the function of liver in treated animals with DOX + honey and reduced the pathological effects of DOX on the above morphological symptoms as well as in the hepatocytes. It is concluded that the ingestion of natural honey has a protective potency against the toxic effects of DOX.
Cite this paper
Ganash, M. , Mujallid, M. , Al-Robai, A. and Bazzaz, A. (2014) Cytoprotectivity of the natural honey against the toxic effects of Doxorubicin in mice. Advances in Bioscience and Biotechnology, 5, 252-260. doi: 10.4236/abb.2014.53032.
Ganash, M. , Mujallid, M. , Al-Robai, A. and Bazzaz, A. (2014) Cytoprotectivity of the natural honey against the toxic effects of Doxorubicin in mice. Advances in Bioscience and Biotechnology, 5, 252-260. doi: 10.4236/abb.2014.53032.
References
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http://dx.doi.org/10.1097/00000637-200209000-00010 [29] Van Vleet, J.F. and Ferrans, V.J. (1980) Clinical and pathologic features of chronic Adriamycin toxicosis in rabbits, American J Veterinary Research, 41, 1462-1469. [30] Tonks, A.J., Cooper, R.A., Jones, K.P., Blair, S., Parton, J. and Tonks, A. (2003) Honey stimulates inflammatory cytokine production from monocytes. Cytokine, 21, 242-247. http://dx.doi.org/10.1016/S1043-4666(03)00092-9 [31] Al-Waili, N.S. (2003) Effects of daily consumption of honey solution on hematological indices and blood levels of minerals and enzymes in normal individuals. Journal of Medicinal Food, 6, 135-140.
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http://dx.doi.org/10.1078/0940-2993-00255 [43] Saad, S.Y. and Najjar, T.A. and AL-Rikabi, A.C. (2001) The preventive role of deferoxamine against acute Doxorubicin induced cardiac, renal and hepatic toxicity in rats. Pharmacological Research, 43, 211-218.
http://dx.doi.org/10.1006/phrs.2000.0769 [44] Nagai, T., Sakai, M., Inouec, R., Inouec, H. and Suzuki, N. (2001) Antioxidative activities of some commercially honeys, royal jelly and propolis. Food Chemistry, 75, 237-240. http://dx.doi.org/10.1016/S0308-8146(01)00193-5 [45] Psotova, J., Chlopcikova, S., Miketova, P., Hrbac, J. and Simanek, V. (2004) Chemoprtective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part III. Apigenin, baicalelin, kaempherol, luteolin, and quercetin. Phytotherapy Research, 18, 516-521.
[1] Lomovskaya, N., Otten, S.L., Doi-Katayama, Y., et al. (1999) Doxorubicin overproduction in Streptomyces peucetius: Cloning and characterization of the dnrU ketoreductase and dnrV genes and the doxA cytochrome P-450 hydroxylase gene. Journal of Bacteriology, 181, 305-318. [2] Laginha, K.M. (2007) Determination of doxorubicin levels in whole tumor and tumor nuclei in murine breast cancer tumors. Clinical Cancer Research, 11, 6944-6949. [3] Liu, Q.-Y. and Tan, B.K.H. (2003) Relationship between anti-oxidant activities and doxorubicin-induced lipid peroxidtion in P388 tumour cells and heart and liver in mice, Clinical and Experimental Pharmacology and Physiology, 30, 185-188.
http://dx.doi.org/10.1046/j.1440-1681.2003.03803.x [4] Zima, T., Tesar, V., Richardson, P.J., Mantle, D. and Preedy, V.R. (2001) Effects of doxorubicin (adriamycin) and [(1)-1,2-Bis(3,5-dioxopiperazinyl-1yl)]propane (ICRF-187) on skeletal muscle protease activities. Toxicology and Applied Pharmacology, 171, 135-140.
http://dx.doi.org/10.1006/taap.2000.9084 [5] Kaczmarek, A., Brinkman, B.M., Heyndrickx, L., Vandenabeele, P. and Krysko, D.V.J. (2012) Severity of doxorubicin-induced small intestinal mucositis is regulated by the TLR-2 and TLR-9 pathways. The Journal of Pathology, 226, 598-608. [6] Friedman, R., Caflisch, A. (2009) Discovery of plasmepsin inhibitors by fragment-based docking and consensus scoring. ChemMedChem, 4, 1317-1326.
http://dx.doi.org/10.1006/taap.2000.9084 [7] Gamo, F.-J. et al. (2010) Thousands of chemical starting points for antimalarial lead identification. Nature, 465, 305-310. http://dx.doi.org/10.1038/nature09107 [8] Quiles, J., Huertas. J., Battino, M., Mataix, J. and Ramirez, T.M. (2002) Antioxidant nutrients and Adriamycin toxicity. Toxicology, 180, 79-95.
http://dx.doi.org/10.1016/S0300-483X(02)00383-9 [9] Reszka, K.J., Mccormick, M.L. and Britigan, B.E. (2003) Oxidation of anthracycline anticancer agents by the peroxidase mimic microperoxidase 11 and hydrogen peroxide, free radical. Biology & Medicine, 35, 78-93.
http://dx.doi.org/10.1016/S0891-5849(03)00238-7 [10] De Beer, E.L., Antonio, E. and Vooest, E.E. (2001) Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: A Review. European J. of Pharmacology, 415, 1-11.
http://dx.doi.org/10.1016/S0014-2999(01)00765-8 [11] Basser, R.L. and Green, M.D. (1993) Strategies for prevention of anthracycline cardiotoxicity, Cancer Treatment Reviews, 19, 57-77.
http://dx.doi.org/10.1016/0305-7372(93)90027-O [12] Kocak, G., Erbil, K.M., Özdemir, I. Aydemir, S., Sunar, B., Tuncel, M. and Atalay, S. (2003) The protective effect of melatonin on Adriamycin-induced acute cardiac injury. Canadian Journal of Cardiology, 19, 535-541. [13] Klimtova, I., Simunek, T., Mazurova, Y., Hrdina, R. Gersl, V. and Adamcova, M. (2002) Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits. Human & Experimental Toxicology, 21, 649-657. http://dx.doi.org/10.1191/0960327102ht311oa [14] Mostafa, M.G., Mima, T. and Koreaki, M. (2000) S-allylcysteine ameliorates doxorubicin toxicity in the heart and liver in mice. Planta Medica, 66, 148-151.
http://dx.doi.org/10.1055/s-2000-11124 [15] Candussio, L., Decorti, G., Crivellato, E., Granzotto, M., Rosati, A., Giraldi, T. and Bartoli, F. (2002) Toxicologic and pharmacokinetic study of low doses of verapamil combined with doxorubicin. Life Sciences, 71, 3109-3119.
http://dx.doi.org/10.1016/S0024-3205(02)02175-6 [16] Kang, J.K., Lee, Y.J., No, K.-O., Jung, E.Y., Sung, J.H. Kim, Y.B. and Nam, S.Y. (2002) Ginseng intestinal metabolite-1(GIM-I) reduces doxorubicin toxicity in the mouse testis. Reproductive Toxicology, 16, 291-298.
http://dx.doi.org/10.1016/S0890-6238(02)00021-7 [17] Wahdan, H.A. (1998) Causes of the antimicrobial activity of Honey. Infection, 26, 26-31.
http://dx.doi.org/10.1007/BF02768748 [18] Cooper, R. and Molan, P. (1999) The use of Honey as an antiseptic in managing Pseudomonas infection, Journal of Wound Care (England), 8, 161-164. [19] Zeina, B., Othman, O. and AL-Assad, S. (1996) Effect of Honey versus thyme on Rubella virus survival in vitro. Journal of Alternative and Complementary Medicine (United States), 2, 345-348.
http://dx.doi.org/10.1089/acm.1996.2.345 [20] Dunford, C., Cooper, R., Molan, P. and White, R. (2001) The use of Honey in wound management. Nursing Standard (Royal College of nursing Great Britain, England), 15, 63-68. [21] Kingslry, A. (2001) The use of Honey in the treatment of infected wounds: Case studies. British J of Nursing (England), 10(22), 13-16. [22] Elawadan, K.M.E. and El-Drieny, E.A. (2000) In vitro study of various types of Honey and Bee pollen upon different malignant cell line. Journal of Neuro-Oncology, 2, 52. [23] Efem, S.E., Udoh, K.T. and Iwara, C.I. (1992) The antimicrobial spectrum of Honey and its clinical significance. Infection (Germany), 20, 227-229.
http://dx.doi.org/10.1007/BF02033065 [24] Vardi, A., Barzilay, Z., Linder, N., Cohen, H.A., Paret, G. and Barzilai, A. (1998) Local application of Honey for treatment of neonatal postoperative wound infection. Acta Paediatrica, 87, 429-432.
http://dx.doi.org/10.1111/j.1651-2227.1998.tb01473.x [25] Gribel, N.V. and Pashinskii, V.G. (1990) The antitumour properties of Honey. Vopr Onkol, 36, 704-709. [26] Frank, C.L. (1991) Basic toxicology fundamentals, target organs, and risk assessment. 2nd Edition, Hemisphere Publishing Corporation, New York, 77-99. [27] Windholz, M. (1976) The Merck index an encyclopedia of chemicals and drugs. 9th Edition, Merck and CO, Inc., Rahway, 1313. [28] Askar, I., Erbas, M.K. and Gurlek, A. (2002) Effect of heparin fractions on the prevention of skin necrosis resulting from adriamycin extravasation: An experimental study. Annals of Plastic Surgery, 49, 297-301.
http://dx.doi.org/10.1097/00000637-200209000-00010 [29] Van Vleet, J.F. and Ferrans, V.J. (1980) Clinical and pathologic features of chronic Adriamycin toxicosis in rabbits, American J Veterinary Research, 41, 1462-1469. [30] Tonks, A.J., Cooper, R.A., Jones, K.P., Blair, S., Parton, J. and Tonks, A. (2003) Honey stimulates inflammatory cytokine production from monocytes. Cytokine, 21, 242-247. http://dx.doi.org/10.1016/S1043-4666(03)00092-9 [31] Al-Waili, N.S. (2003) Effects of daily consumption of honey solution on hematological indices and blood levels of minerals and enzymes in normal individuals. Journal of Medicinal Food, 6, 135-140.
http://dx.doi.org/10.1089/109662003322233549 [32] Zaghloul, A.A., El-Shattawy, H.H., Kassem, A.A., Ibrahim, E.A., Reddy, I.K. and Khan, M.A. (2001) Honey, a prospective antibiotic: Extraction, formulation, and stability. Pharmazie, 56, 643-646. [33] Mitchell, E.P. and Philip, S. (1992) Gastrointestinal toxicity of chemotherapeutic agent. In: Perry, M.C., Ed., The Chemotherapy Source Book, Williams and Wilkins, Baltimore, 620-634. [34] Melichar, B., Kohout, P., Bratova, M., Solichova, D., Kralickova, P. and Zadak, Z. (2001) Intestinal permeability in patients with chemotherapy-induced stomatitis. Journal of Cancer Research and Clinical Oncology, 127, 314-318. http://dx.doi.org/10.1007/s004320000209 [35] Herman, E., Zhang, J., Hasinoff, B.B., Clark Jr., J.R. and Ferrans, V.J. (1997) Comparison of the structural changes induced by doxorubicin and mitoxantrone in the heart, kidney and intestine and characterization of the fe(III)-mitoxantrone complex. Journal of Molecular and Cellular Cardiology, 29, 2415-2430.
http://dx.doi.org/10.1006/jmcc.1997.0477 [36] Pearlman, M., Jendiroba, D., Pagliaro, L., Keyhani, A., Liu, B., Freireich, E.J. and Travis, E. (2003) Dexrazoxane’s protection of jejunal crypt cells in the jejunum of C3Hf/Kam mice from doxorubicin induced toxicity. Cancer Chemotherapy and Pharmacology, 52, 477-481.
http://dx.doi.org/10.1007/s00280-003-0655-3 [37] Urwi, N.S. (2012) Studies of the effects of aspartame on mice liver. MSc Thesis, University of Taibah, KSA Madina. [38] Samelis, G.F., Stathopoulos, G.P., Kotsarelis, D., Dontas, I., Frangia, C. and Karayannacos, P.E. (1998) Doxorubicin cardiotixicity and serum lipid increase is prevented by Dextrazoxane (ICRF-187). Anticancer Research, 18, 3305-3310. [39] Ringenberg, Q.S. (1992) Vascular toxicity. In: Perry, M.C., Ed., The Chemotherapy Source Book, Williams and Wilkins, Baltimore, 680-688. [40] Kandil, A. and Monir, A. (1986) The effect of Honey on pathologic liver. 4th International Conference on Islamic Medicine, Kuwait, Bulletin of Islamic Medicine, 4, 72-77.
https://getinfo.de/app/ISLAMIC-MEDICAL-THEORY-OF-PREVENTION-AND-TREATMENT/id/BLCP%3ACN069421853 [41] Gershbein, L.L. (1976) Liver regeneration in rats administered high levels of carbohydrates. International Journal for Vitamin and Nutrition Research, 46, 472-479. [42] Gharzouli, K., Smain, A., Gharzouli, A. and Khennouf, S. (2002) Gastroprotective effects of Honey and glucosefructose-sucrosemaltose mixtureagainst ethanol, indomethacin, and acidified aspirin-induced lesions in the rat. Experimental and Toxicologic Pathology, 54, 217-221.
http://dx.doi.org/10.1078/0940-2993-00255 [43] Saad, S.Y. and Najjar, T.A. and AL-Rikabi, A.C. (2001) The preventive role of deferoxamine against acute Doxorubicin induced cardiac, renal and hepatic toxicity in rats. Pharmacological Research, 43, 211-218.
http://dx.doi.org/10.1006/phrs.2000.0769 [44] Nagai, T., Sakai, M., Inouec, R., Inouec, H. and Suzuki, N. (2001) Antioxidative activities of some commercially honeys, royal jelly and propolis. Food Chemistry, 75, 237-240. http://dx.doi.org/10.1016/S0308-8146(01)00193-5 [45] Psotova, J., Chlopcikova, S., Miketova, P., Hrbac, J. and Simanek, V. (2004) Chemoprtective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part III. Apigenin, baicalelin, kaempherol, luteolin, and quercetin. Phytotherapy Research, 18, 516-521.