Cranberry Extract as a Supplemented Food in Treatment of Oxidative Stress and Breast Cancer Induced by N-methyl-N-nitrosourea in Female Virgin Rats

Authors

  • Sylvia A. Boshra Biochemistry Department, Faculty of Pharmacy, October 6 University, 6th of October City, Egypt
  • Mohammed Abdalla Hussein Biochemistry Department, Faculty of Pharmacy, October 6 University, 6th of October City, Egypt .

Keywords:

MNU, tamoxifen, cranberry extract, breast cancer, liver, mammary tissue

Abstract

Breast cancer is the most common cancer and a major cause of death in women. The present study was designed to evaluate the antioxidant and anticancer potential of cranberry extract against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in rats. The tumor was induced in Female virgin rats of age 50 days by single dose of MNU (50mg/kg.b.w i.p.). After 85 days; all rats developed at least one tumor. Animals were treated with cranberry extract (400 and 600 mg/kg.b.w.orally) and tamoxifen (2mg/kg.b.w. i.p) for 4 weeks (from day 86 to day 113). MNU treatment resulted in a significant decrease (p < 0.05) in blood hemoglobin (Hb), red blood cells (RBC), platelets (PLTs) as well as blood, liver and breast catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). However, MNU treatment resulted in a significant increase in White blood cells (WBC) as well as plasma, liver and mammary tissue gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), hexosamine, sialic acid and thiobarbituric acid reactive substances (TBARs). Upon administration of the cranberry extract, the levels of WBC, GGT, LDH, hexosamine, sialic acid, TBARs, Hb, RBC, PLTs, CAT, GPx and SOD were significantly normalized. Histopathological changes also confirmed the formation of tumor tubules and neovascularization after the MNU treatment. Cranberry extract administration significantly reduces the growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development. Comparing the beneficial effect of cranberry extract with that of MNU-induced breast cancer, cranberry extract showed antitumor and antioxidant activity indicated by the measured biochemical parameters and the histopathological examination of mammary tissue. The results of the present study indicate that cranberry extract possesses strong anticancer effects through its role in modulating glycoprotein components and the levels of oxidative stress biomarkers. Cranberry exerted a stronger anticancer effect at the dosage of 600 mg/kg body weight than at dosage 400 mg/kg body weight.

References

Cameron D and Bell R. Optimizing treatment for patients with breast cancer. Seminar in Oncol 2004; 31: 4-5.

Schultz LB and Weber BL. Recent advances in breast cancer biology. Curr Opin Oncol 1999; 11: 429-434.

Alexandrov VA and Bespalov VG. Preclinical and clinical study of cancer chemopreventive agents. St. Petersburg: Esculap 1997; 32 (in Russian).

Kelloff GJ. Perspectives on cancer chemoprevention research and drug development. Adv Cancer Res 2000; 78: 199-334.

Fisher B, Costantino JP and Wickerham DL. Tamoxifen for prevention of breast cancer: current status of the national surgical adjuvant breast and bowel project P-1 study. Journal of the national cancer institute 2005; 97:1652-1662.

Loo SA, Lesoon-Wood LA and Cooney RV. Effects of tamoxifen on nitric oxide synthesis and neoplastic transformation in C3H 10T1/2 fibroblasts. Cancer Lett 1998; 122: 67–75.

Elefsiniotis I, Pantazis K, Ilias A, Pallis L, Mariolis A, Glynou I, Kada H and Moulakakis A. Tamoxifen induced hepatotoxicity in breast cancer patients with preexisting liver steatosis: the role of glucose intolerance. Eur J Gastroenterol Hepatol 2004; 16:593–598.

Manach C, Scalbert A, Morand C, Rémésy C and Jiménez L. Polyphenols: food sources and

bioavailability. The American Journal of Clinical Nutrition 2004;79:727-747.

Santos-Buelga C and Scalbert A. Proanthocyanidins and tannin-like compounds: nature, occurrence, dietary intake and effects on nutrition and health. Journal of the Science of Food and Agriculture 2000;80:1094-1117.

Porter, ML., Krueger, CG., Wiebe, DA., Cunningham, DG. and Reed, JD. Cranberry proanthocyanidins associate with low-densitylipoprotein and inhibit in vitro Cu2 1 -induced oxidation. J Sci Food Agric., 2001; 81: 1306–13.

Vinson, JA., Su, X., Zubik, L. and Bose P. Phenol antioxidant quantity and quality in foods: Fruits.J. Agric. Food Chem., 2001;49:5315–21.

Yan, X., Murphy, B.T., Hammond, G.B., Vinson, J.A. and Neto CC. Antioxidant activities and antitumor screening of extracts from cranberry fruit (Vaccinium macrocarpon). J Agric Food Chem., 2002; 50: 5844–9.

Neto, CC., Sweeney-Nixon, MI., Lamoureaux, TL., Solomon, F., Kondo, M. and MacKinnon, SL.Cranberry phenolics: Effects onoxidative processes, neuron cell death and tumor cell growth. In Shahidi F, Ho C-T, editors. Symposium Series No. 909:Phenolic Compounds in Foods and Natural Health Products Columbus, OH: ACS Books; 2005; 271 –282.

Youdim, KA., McDonald, J., Kalt, W. and Joseph, JA. Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults. J Nutr Biochem., 2002;13: 282–8.

Ebrahimzadeh, MA., Nabavi, SF. and Nabavi, SM. Essential oil composition and antioxidant activity of Pterocarya fraxinifolia. Pak JBiol Sci., 2009; 12: 957–963.

da Silva, NA., da Silva, JK., Andrade, EH., Carreira, LM., Sousa, PJ. and Maia, JG. Essential oil composition and antioxidant capacity of Lippia schomburgkiana. Nat Prod Commun 2009; 4:1281 –1286.

De´corde,´ K., Agne, A., Lacan, D., Ramos, J., Fouret, G., Ventura E., Feillet-Coudray, C., Cristol, JP. and Rouanet, JM. Preventive effect of melon extract rich in superoxide scavenging activity onabdominal and liver fat and adipokine imbalance in high-fat-fedhamsters. J Agric Food Chem.,2009;22: 6461 –6467.

Han, SH., Yang, BS. and Kim, HJ. Effectiveness of aromatherapy massage on abdominal obesity among middle aged women. J KoreanAcad Nurss. 2003; 33:839–846.

Abdel-Maksoud, HA, Hussein, MA, Mohammed, RR. and Zayed, HT. Cranberry extract Enhance antioxidant Potential in Ehrlich’s Ascites Carcinoma–Bearing Female Albino Mice. World Journal of Pharmaceutical Sciences. 2015; 3(3): 484-491.

Abdel-Maksoud, HA., Hussein, MA. and Barakat, MA. Cranberry Extract as a Functional Food in Treatment of Myocardial Toxicity Induced by nicotine in Rats. International Journal of Pharma Sciences. 2015; 4: 1174-1180.

Hussein MA and Boshra SA. Anti-leukopenic and Antioxidant Effects of Cranberry Extract in Benzene and fluorouracil induced leukopenia in Rats. IJARNP, 2015; inpress.

Gotoh T, Yamada K, Ito A, Yin H, Kataoka T and Dohi K. Chemoprevention of N-nitroso-N-methylurea-induced rat mammary cancer by miso and tamoxifen, alone and in combination. Jpn J Cancer Res 1998; 89: 487-495.

Jain WC: Schalm's Veterinary Hematology, ed 4, Lea and Febiger, Philadelphia. 1986, pp. 69 - 71.

Rosalki SB, Rau D: Serum gamma glutamyl transpeptidase activity in alcoholism. Clin Chim Acta 1972; 39: 41-47.

Buhl SN, Jackson KY. Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate to pyruvate to lactate reactions in human serum at 25, 30 and 37 0C. Clin. Chem. 1978; 2415: 828.

Wagner WD: More sensitive assay discriminating galactosamine and glucosamine in mixtures. Anal biochem 1979; 94:394-397.

Niebes P: Determination of enzyme and degradation products of GAG metabolism in the serum of healthy and various subjects. Clin Chim Acta 1972; 42: 399-408.

Sinha, AK. Colorimetric assay of catalase. J.AnalBiochem. 1972; 47 (2): 389-94.

Paglia D, Valentine W. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med 1967; 70:158.

Suttle N. Copper deficiency in ruminants; recent developments. The Veterinary Record. 1986; 119: 519-22.

Nichans WH, Samulelson B. Formation of malondialdehyde from phospholipid arachidonateduring microsomal lipid peroxidation. Eur J Biochem1968; 6: 126-30.

Lowry OH, Rosebrough NJ, Farr AL, Randall R: Protein measurement with Folin’s phenol reagent. J Biol Chem 1952; 193: 265-275.

Horn HD, Burns FH. Assay of glutathione reductase activity. In: Bergmeyer HV (Ed.), Methods of Enzymatic Analysis. Academic Press, New York, USA, 1 978; pp. 1 42-1 46.

Sedlak J, Lindsay RH1968. Estimation of total protein bound and nonprotein sulfhydryl group in tissue with Ellman’s reagents. Analyst Biochem 1968; 25: 192–205.

Bancroft GD, Steven A. In. Theory and practice of histological technique 4th Ed. London; Churchill Livingstone. 1983; Pp. 99 – 112.

Abo-Allam, R.M., 2003. Data Statistical Analysis using SPSS Program. 1 Ed., Publication for 1stUniversities, Cairo.

Rajarshi R, Mitali G, Kartick S and Malay C. Vanadium, a versatile biochemical effector in chemical rat mammary carcinogenesis. Nutrition and Cancer 2005; 51(2): 184–196.

Gusterson BA and Williams JC. N-nitrosomethylurea-induced rat mammary tumours as models of human breast cancer. J R Soc Med 1981; 74: 56-59.

Angelopoulos N, Barbounis V, Livadas S, Kaltsas D and Tolis G. Effects of estrogen deprivation due to breast cancer treatment. Endocr Relat Cancer 2004; 11: 523-535.

Jo EH, Hong HD, Ahn NC, Jung JW, Yang SR and Park JS. Modulations of the Bcl-2/Bax family were involved in the chemopreventive effects of licorice root (Glycyrrhiza uralensis Fisch) in MCF-7 human breast cancer cell. J Agric Food Chem 2004; 52: 1715-1719.

Ivanova D, Gerova D, Chervenkov T and Yankova T. Polyphenols and antioxidant capacity of Bulgarian medicinal plants. J Ethnopharmacol 2005; 96: 145-150.

Takahashi H, Uemura Y, Nakao I and Tsubura A. Induction of mammary carcinomas by the direct application of crystalline N-methyl-N-nitrisourea onto rat mammary gland. Cancer Lett. 1995;92:105-11.

Thompson HJ, McGinley JN, Rothhammer K and Singh M. Rapid induction of mammary intraductal proliferations, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis.1995; 16:2407-411.

da Silva Franchi CA, Bacchi MM, Padovani CR and de Camargo JL. Thymic lymphomas in Wistar rats exposed to N-methyl-N-nitrosourea (MNU). Cancer Sci. 2003;94(3):240- 43.

Akanni EO, Oloke JK and Fakunle EE. Haematological characterization in N-nitroso-N- ethylurea induced tumour bearing rats on oral administration of pleurotus pulmonarius and pleurotus ostreatus metabolites. IJRRAS. 2010; 3(3):343-48.

Vinson JA, Su X, Zubik L, Bose P. Phenol antioxidant quantity andquality in foods: Fruits. J. Agric. Food Chem., 2001;49:5315–21.

Yan X, Murphy BT, Hammond GB, Vinson JA, Neto CC. Antioxidantactivities and antitumor screening of extracts from cranberry fruit(Vacciniummacrocarpon). J Agric Food Chem., 2002;50:5844–9.

Porter ML, Krueger CG, Wiebe DA, Cunningham DG, Reed JD.Cranberry proanthocyanidins associate with low-density lipoproteinand inhibit in vitro Cu2 1-induced oxidation. J Sci Food Agric., 2001;81:1306–13.

Neto CC, Sweeney-Nixon MI, Lamoureaux TL, Solomon F, Kondo M,MacKinnon SL. Cranberry phenolics: Effects on oxidative processes,neuron cell death and tumorcell growth. In Shahidi F, Ho C-T, editors.Symposium Series No. 909: PhenolicCompounds in Foods and NaturalHealth Products Columbus, OH: ACS Books; 2005; 271–282.

Youdim KA, McDonald J, Kalt W, Joseph JA. Potential role of dietary flavonoids in reducing microvascular endothelium vulnerability to oxidative and inflammatory insults. J NutrBiochem., 2002;13:282–8.

Mishra S, Sharma DC and Sharma P. Studies of biochemical parameters in breast cancer with and without metastasis. Indian J. Clin. Biochem. 2004; 19: 71-75.

Wang JY, Xu BH, Tian LJ and Wang Y. Clinical characteristics and potential prognostic factors of breast cancer patients with liver metastases. Zhonghua Zhong Liu. Za. Zhi. 2006; 28: 612-616.

Lynch ED, Gu R, Pierce C and Kil J. Combined oral delivery of ebselen and allopurinol reduces multiple cisplatin toxicities in rat breast and ovarian cancer models while enhancing anti-tumor activity. Anticancer Drugs, 2005; 16: 569-579.

Koukourakis MI, Kontomanolis E, Giatromanolaki A, Sivridis E and Liberis V. Serum and Tissue LDH Levels in Patients with Breast/Gynaecological Cancer and Benign Diseases. Gynecol. Obster. Invest. 2006; 67: 162-168.

Perumal SS, Shanthi P and Sachdanadam P. Therapeutic effect of tamoxifen and energy-modulating vitamins on carbohydrate metabolizing enzymes in breast cancer. Cancer Chemother. Pharmacol. 2005; 56: 105-114.

Strasak AM, Pfeiffer RM, Klenk J, Hilbe W, Oberaigner W, Gregory M, Concin H, Diem G, Pfeiffer KP, Ruttmann E and Ulmer H. Prospective study of the association of gamma-glutamyltransferase with cancer incidence in women. Int. J. Cancer, 2008; 123: 1902-1906.

Sani HA, Rahmat A, Ismail M, Rosli R and Endrini S. Potential anticancer effect of red spinach (Amaranthus gangeticus) extract. Asia Pac. J. Clin. Nutr. 2004; 13: 396-400.

Chanet A, Milenkovic D, Manach C, Mazur A and Morand C. Citrus flavanones: what is their role in cardiovascular protection, J. Agric. Food Chem. 2012; 60:8809–8822.

Kannampalli P, Sang HP and Kyong CK. Hesperidin a flavanoglycone protects against -irradiation induced hepatocellular damage and oxidative stress in Sprague Dawley rats, Eur. J. Pharmacol. 2008; 587: 273–280.

Sies H. Oxidative stress, oxidants and antioxidants, Exp. Physiol. 1997; 82: 291–295.

Veerappan RM, Senthil S, Rao MR and Ravikumar R. Redox status and lipid peroxidation in alcoholic hypertensive patients and alcoholic hypertensive patients with diabetes, Clin. Chem. Acta 2004; 340: 207–212.

Jensen ON, Estene J and Moller H. Renardcarin the European community and members state. Eur J Cancer 1990; 26: 1167-1256.

Bolt HM, Filser JG. Irreversible binding of chlorinated ethylenels to macromolecules. Environ Health Perspect 1977; 21: 107-112.

Hughes RC. Membrane glycoproteins. Butterworth, London, 1976. pp: 114-134, 152-170.

Selvam S and Nagini S. Administration of the plasticizer di(englhexyl)phthalate alters glycoconjugate profile. Ind J Physiol Pharmocol 1995; 39: 252-254.

Schauer R. Sialic acids and their role as biological masks. Trends Biochem Sci 1985; 10: 357-360.

Wongkham S, Bhudhisawadi V, Chau-in S, Boonla C, Muisuk K, Kongkham S and Wongkham C. Clinical significance of serum total sialic acid in cholangiocarcinoma. Clin Chim Acta 2003; 327(1-2): 139-147.

Singhal A and Hakomori S. Molecular changes in carbohydrate antigens associated with cancer. Bioassays 1990; 12: 223-230.

King RS, Teitel CH, Shaddock JG, Casciano DA and Kadlubar FF. Detoxification of carcinogenic aromatic and heterocyclic amines by enzymatic reduction of the N-hydroxy derivative. Cancer Lett 1999; 143(2): 167-71.

Sato K. Glutathione s-transferase as markers of preneoplasia and neoplalsia. Adv Cancer Res 1989; 52: 205-255.

Oakley A. Glutathione transferases: a structural perspective. Drug Metab Rev 2011; 43(2): 138–51.

Suhel P, Heena T, Hasibur R, Basu Dev B, Mohammad A, Sheikh R. Catechin prevents tamoxifen-induced oxidative stress and biochemical perturbations in mice. Toxicology 2006; 225:109–118.

Hesham AE, Ahmed MM, Ayman AN, Ashraf BA. Amelioration of tamoxifen-induced liver injury in rats by grape seed extract, black seed extract and curcumin. Experimental biology.(2010);48,280-288.

Hesham AE. The effect of dimethyl dimethoxy biphenyl dicarboxylate (DDB) against tamoxifen-induced liver injury in rats: DDB use Is curative or protective. J Biochem Mol Biol 2005; 38: 300-306.

Diplock AT, Rice CA and Burdon RH. Is there a significant role for lipid peroxidation in the causation of malignancy and for antioxidants in cancer prevention.

Cancer Res 1994; 54: 1952-1956.

Lee CP, Shih PH, Hsu CL and Yen GH. Hepatoprotection tea seed oil (Camellia oleifera Abel) against CCl4- induced oxidative damage in rats. Food and chem

toxicol 2007; 45: 888-893.

Deisseroth A and Dounce AL. Catalase: physical and chemical properties, mechanism of catalysis. Physiological role, Physiol. Rev. 1970; 50:319–375.

Deneke, SM. and Fanburg, BL. Regulation of cellular glutathione, Am. J. Physiol. Lung Cell Mol. Physiol. 1989; 257:163–173.

Eaton, JW. Catalase, glutathione peroxidase and hydrogen peroxidase, J. Clin. Lab. Med. 1993; 118:3–4.

Tirkey N, Pilkhwal S, Kuhad A and Chopra K. Hesperidin, a citrus bioflavonoid, and decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney, BMC Pharmacol. 2005; 5: 2-8.

Winker BS. Unequivocal evidence in support of non enzymatic redox coupling between glutathione/glutathione disulphide and ascorbic acid/dehydroascorbic acid, Biophys. Acta 1992; 117:287–290.

Choi SW, Benzic IFE, Collins AR and Hannigan RM. Vitamin C and E: acute interactive effects on biomarkers of antioxidant defence and oxidative stress, Mut. Res.2004; 551:109–117.

Downloads

Published

30-06-2016

How to Cite

1.
Sylvia A. Boshra, Mohammed Abdalla Hussein. Cranberry Extract as a Supplemented Food in Treatment of Oxidative Stress and Breast Cancer Induced by N-methyl-N-nitrosourea in Female Virgin Rats. ijp [Internet]. 2016 Jun. 30 [cited 2024 Oct. 8];8(2):217-2. Available from: https://ijp.arjournals.org/index.php/ijp/article/view/461

Issue

Section

Original Research Articles