THE POSSIBLE CARDIOPROTECTIVE EFFECTS OF DIFFERENT FRACTIONS OF ARTICHOKE EXTRACTS AGAINST 5-FU INDUCED CARDIOTOXICITY IN ALBINO RATS

Authors

  • Safa Mustafa Najim Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq
  • Intesar T. Numan University of Baghdad
  • Maha N. Hamad University of Baghdad

Keywords:

Artichoke extracts, 5-fluorouracil, Cardioprotective, Cardiac troponin T, TNF-a and T-AOC

Abstract

Objective: The present study aimed to evaluate the cardioprotective effects of ethyl acetate and methanolartichoke extracts(Cynara scolymus L.) against 5-Flurouracil (5-FU) induced cardiotoxicity in rats.

Methods: Thirty-six albino rats were divided randomly and equallyin to six groups (each group with 6 rats): I, negative control, received (2 ml/kg/d)of dimethyl sulfoxide (DMSO) orally for 30 successive d; II, positive control, received (2 ml/kg/d) of (DMSO) orally for 30 successive d, and subsequently administered a single dose of 5-FU (150 mg/kg) by intraperitoneal injection on 27thd in assossiation with DSMO; III and V, received (200 mg/kg/d) of oral methanol and ethyl acetate artichoke extracts respectivelyfor 30 successive d; V and VI, received(200 mg/kg/d) of oral methanol and ethyl acetate artichoke extracts respectively for 30 successive d,with a subsequently received single dose of 5-FU (150 mg/kg) by intraperitoneal injection on 27th d of the experiment.

Results: Prophylactic treatment of ethyl acetate and methanol artichoke extracts significantly attenuates the increased level of serum cardiac troponin T (CTn-T) and tumor necrosis factor-a(TNF-a)caused by 5-FU-induced cardiotoxicity in experimental albino rats while it increases the serum level of total antioxidant capacity (T-AOC).

Conclusion: Results of the present study suggest that methanol and ethyl acetate artichoke extracts may be an effective modulator in mitigating 5-FU induced cardiotoxicity.

 

Downloads

Download data is not yet available.

References

Kovach JS, Beart RW. Cellular pharmacology of fluorinated pyrimidines in vivo in man. Invest New Drugs 1990;7:13–25.

Grem JL. 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs 2000;18:299-313.

Mohammad abdul amir ulaiwy and mohammed hassan mohammed. synthesis of azo derivatives of 5-fluorouracil for possible targeting of colon cancer. J Adv Chem 2014;7:1258.

Zhang N, Yin Y, Xu SJ, Chen WS. 5-fluorouracil: mechanisms of resistance and reversal strategies. Molecules 2008;13:1551-69.

Arias JL, Ruiz MA, López-Viota M, Delgado AV. Poly (alkylcyanoacrylate) colloidal particles as vehicles for antitumour drug delivery: a comparative study. Colloids Surf B 2008;62:64-70.

Costi MP, Ferrari S, Venturelli A, Calo S, Tondi D, Barlocco D. Thymidylate synthase structure, function and implication in drug discovery. Curr Med Chem 2005;12:2241–58.

Yu BT, Sun X, Zhang ZR. Enhanced liver targeting by synthesis of N1-stearyl-5-FU and incorporation into solid lipid nanoparticles. Arch Pharm Res 2003;26:1096–101.

Summya Rashid, Nemat Ali, Sana Nafees, Syed Kazim Hasan, Sarwat Sultana. Mitigation of 5-Fluorouracil induced renal toxicity by chrysin via targeting oxidative stress and apoptosis in wistar rats. Food Chem Toxicol 2014;66:185–93.

Marakis G, Walker AF, Middleton RW, Booth JC, Wright J, Pike D, et al. Artichoke leaf extract reduces mild dyspepsia in an open study. Phytomedicine 2002;9:694-9.

Maria Rosario ALONSO; Maria del Carmn GARCIA Claudia Garcia BONELLI: Validated HPLC Method for Cynarin Dctermination in Biological Sample: Acta Farm. Bonaerense 2006;25:267–70.

Mulinacci N, Prucher D, Peruzzi M, Romani A, Pinelli P, Giaccherini C, et al. Commercial and laboratory extracts from artichoke leaves: estimation of caffeoyl esters and flavonoidic compounds content. J Pharm Biomed Anal 2004;34:349-57.

Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food. Drugs and Cosmetics. 2nd ed. NewYork: John Wiley and Sons, Inc; 1996. p. 4244.

Speroni E, Cervellati R, Govoni P, Guizzardi S, Renzulli C, Guerra MC. Efficiency of different Cynara scolymus preparations liver complaints. J Ethnopharmacol 2003;8:203–11.

Zhu X, Zhang H, Lo R. Phenolic Compounds from the leaf extract of artichoke (Cynara scolymus) and their antimicrobial activities. J Agric Food Chem 2004;52:7272–8.

Küskü-Kiraz Z, Mehmetçik G, Dogru-Abbasoglu S, Uysal M. Artichoke leaf extract reduces oxidative stress and lipoprotein dyshomeostasis in rats fed on high cholesterol diet. Phytother Res 2010;24:565-70.

Zapolska-Downar D, Zapolski-Downar A, Naruszewicz M, Siennicka A, Krasnodebska B, Kolodziej B. Protective properties of artichoke (Cynara scolymus) against oxidative stress induced in cultured endothelial cells and monocytes. Life Sci 2002;71:2897–908.

Jimenez-Escrig A, Dragsted LO, Daneshvar B, Pulido R, Saura Calixto F. In vitro Antioxidant activities of edible artichoke (Cynara scolymus L.) and effect on biomarkers of antioxidants in rats. J Agric Food Chem 2003;51:5540–5.

Ramachandran S Vasan, Lisa M Sullivan, Ronenn Roubenoff, Charles A Dinarello, Tamara Harris, Emelia J Benjamin, et al. Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction the framingham heart study. Circulation 2003;107:1486-91.

Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancerpatients treated with 5-fluorouracil or capecitabine: a systematic reviewof incidence, manifestations and predisposing factors. Cancer Treat Rev 2013;39:974–84.

Kosmas C, Kallistratos MS, Kopterides P, Syrios J, Skopelitis H, Mylonakis N, et al. Cardiotoxicity offluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol 2008;134:75–82.

Meydan N, Kundak I, Yavuzsen T, Oztop I, Barutca S, Yilmaz U, et al. Cardiotoxicity of de Gramont’s regimen: incidence, clinical characteristics and long-term follow-up. Jpn J Clin Oncol 2005;35:265–70.

Meyer CC, Calis KA, Burke LB, Walawander CA, Grasela TH. Symptomaticcardiotoxicity associated with 5-fluorouracil. Pharmacotherapy 1997;17:729–36.

Ng M, Cunningham D, Norman AR. The frequency and pattern ofcardiotoxicity observed with capecitabine used in conjunction withoxaliplatin in patients treated for advanced colorectal cancer (CRC). Eur J Cancer 2005;41:1542–6.

Rezkalla S, Kloner RA, Ensley J, al-Sarraf M, Revels S, Olivenstein A, et al. Continuous ambulatory ECG monitoring duringfluorouracil therapy: a prospective study. J Clin Oncol 1989;7:509–14.

Anne Polk1, Kirsten Vistisen, Merete Vaage-Nilsen, Dorte L Nielsen. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol Toxicol 2014;15:47.

Lamberti M, Porto S, Marra M, Zappavigna S, Grimaldi A, Feola D, et al. 5-Fluorouracil induces apoptosis in rat cardiocytes through intracellular oxidative stress. J Exp Clin Cancer Res 2012;31:60.

Durak I, Karaayvaz M, Kavutcu M, Cimen MY, Kacmaz M, Buyukkocak S, et al. Reduced antioxidant defense capacity in myocardial tissue from guinea pigs treated with 5-fluorouracil. J Toxicol Environ Health A 2000;59:585–9.

Sterba M, Popelova O, Vavrova A, Jirkovsky E, Kovarikova P, Gersl V, et al Oxidative stress, redox signaling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection. Antioxid Redox Signaling 2013;18:899–929.

Kehrer JP. The haber-weiss reaction and mechanisms of toxicity. Toxicology 2000;149:43–50.

Kristian Thygesen, Johannes Mair, Hugo Katus, Mario Plebani, Per Venge, Paul Collinson, et al. Recommendations for the use of cardiac troponin measurement in acute cardiac care. Eur Heart J 2010;31:2197–206.

Sylvia Archan, Lee A. Fleisher, From creatine Kinase-MB to troponin. Anesthesiology 2010;112:1005–12.

Pasquale Pignatelli, Roberto Cangemi, Andrea Celestini, Roberto Carnevale, Licia Polimeni, Alessandra Martini, et al. Tumour necrosis factor-α upregulates platelet CD40L in patients with heart failure. Cardiovasc Res 2008;78:515–22.

Doerries C, Grote K, Hilfiker-Kleiner D, Luchtefeld M, Schaefer A, Holland SM, et al. Critical role of the NAD(P)H oxidase subunit p47phox for left ventricular remodeling/dysfunction and survival after myocardial infarction. Circ Res 2007;100:894-903.

Tessa H Wright, Roger Yazbeck, Kerry A Lymn, Eleanor J Whitford, Ker Y Cheah, Ross N Butler, et al. The herbal extract, Iberogast®, improves jejunal integrity in rats with 5-Fluorouracil (5-FU)-induced mucositis. Cancer Biol Ther 2009;8:923-9.

JJ Kim, SB Lee, JK Park, YD Yoo. TNF-a-induced ROS production triggering apoptosis is directly linked to Romo1 and Bcl-XL. Cell Death Differ 2010;17:1420–34.

Corda S, Laplace C, Vicaut E, Duranteau J. Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. Am J Respir Cell Mol Biol 2001;24:762–8.

Chung YM, Kim JS, Yoo YD. A novel protein, Romo1, induces ROS production in the mitochondria. Biochem Biophys Res Commun 2006;347:649–55.

Chung YM, Lee SB, Kim HJ. Replicative senescence induced by Romo1-derived reactive oxygen species. J Biol Chem 2008;283:33763–71.

Lee SB, Kim JJ, Kim TW. Serum deprivation-induced reactive oxygen species production is mediated by Romo1. Apoptosis 2010;15:204–18.

Hwang IT, Chung YM, Kim JJ. Drug resistance to 5-FU linked to reactive oxygen species modulator 1. Biochem Biophys Res Commun 2007;359:304–10.

Kim YS, Morgan MJ, Choksi S, Liu ZG. TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol Cell 2007;26:675–87.

Sakon S, Xue X, Takekawa M. NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J 2003;22:3898–909.

Tobiume K, Matsuzawa A, Takahashi T. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2001;2:222–8.

Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food source and bioavailability. Am J Clin Nutr 2004;79:727–47.

Scalbert A, Manach C, Morand C, Remesy C. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45:287–306.

Gebhardt R. Hepatoprotektion durch extract aun artischoken. Pharm Ztg 1995;43:34-7.

Gebhardt R. Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl Pharmacol 1997;144:279-86.

Rondanelli M, Monteferrario F, Perna S, Faliva MA, Opizzi A. Management strategies and choice of antithrombotic treatment in patients admitted with acute coronary syndrome--executive summary for clinical practice. Consensus Document of the Regional Chapters of the Italian National Association of Hospital Cardiologists (ANMCO) and of the Italian Society of Emergency Medicine (SIMEU). Monaldi Arch Chest Dis 2013;80:7-16.

Li H, Xia N, Brausch I, Yao Y, Forster-mann UJ. Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells. Pharmacol Exp Ther 2004;310:926-32.

Metwally NS, Kholeif TE, Ghanem KZ, Farrag AR, Ammar NM, Abdel-Hamid AH. The protective effects of fish oil and artichoke on hepatocellular carcinoma in rats. Eur Rev Med Pharmacol Sci 2012;15:1429-44.

Miccadei S, Di Venere D, Cardinali A. Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer 2008;60:276-83.

Chen JH, Ho CT. Antioxidant activities of caffeic acid and its related hydroxycinamic acid compounds. J Agric Food Chem 1997;45:2374-8.

Toma´s-Barbera´n FA, Ferreres F, Gil MI. Antioxidant phenolic metabolites from fruit and vegetables and changes during postharvest storage and processing. In: Bioactive Natural Products (Part D); Rahman A. Ed. Elsevier Science: Amsterdam, The Netherlands; 2000. p. 739-95.

Lattanzio V, Cardinali A, di Venere D, Linsalata V, Palmieri S. Browing phenomena in stored artichoke (Cynara scolymus L.) heads: enzymatic or chemical reactions? Food Chem 1994;50:1-7.

Lattanzio V. Attuali conoscenze sui polifenoli del carciofo. In: Studi sul Carciofo; Marzi V, Lattanzio V. Eds. Laterza: Bari, Italy; 1981. p. 13-32.

Lattanzio V, van Sumere CF. Changes in phenolic compounds during the development and cold storage of artichoke (Cynaras colymus L.). Food Chem 1987;24:37-50.

Aubert S, Foury C. Couleur et pigmentation antohicyanique de l’artichaut (Cynara scolymus L.). In: Studi sul Carciofo; Marzi V, Lattanzio V, Eds. Laterza: Bari, Italy; 1981. p. 57-76.

Perez-Garcia F, T Adzet, S Canigueral. Activity of artichoke leaf extract on reactive oxygen species in human leukocytes. Free Radic Res 2000;33:661-5.

Jimenez-Escrig A. In vitro antioxidant activities of edible artichoke (Cynara scolymus L.) and effect on biomarkers of antioxidants in rats. J Agric Food Chem 2003;51:5540-5.

Hille R, T Nishino. Flavoprotein structure and mechanism. 4. Xanthine oxidase and xanthine dehydrogenase. Faseb J 1995;9:995-1003.

Cotelle N. Antioxidant properties of hydroxy-flavones. Free Radic Biol Med 1996;20:35-43.

Scalbert A. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 2005;45:287-306.

Published

01-10-2015

How to Cite

Najim, S. M., I. T. Numan, and M. N. Hamad. “THE POSSIBLE CARDIOPROTECTIVE EFFECTS OF DIFFERENT FRACTIONS OF ARTICHOKE EXTRACTS AGAINST 5-FU INDUCED CARDIOTOXICITY IN ALBINO RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 11, Oct. 2015, pp. 165-9, https://journals.innovareacademics.in/index.php/ijpps/article/view/6707.

Issue

Section

Original Article(s)