Journal of Cancer Research and Treatment
ISSN (Print): 2374-1996 ISSN (Online): 2374-2003 Website: http://www.sciepub.com/journal/jcrt Editor-in-chief: Jean Rommelaere
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Journal of Cancer Research and Treatment. 2016, 4(2), 26-31
DOI: 10.12691/jcrt-4-2-2
Open AccessArticle

Ameliorative Potential of Different Doses of Indol-3-carbinol on Doxorubicin-induced Cardiotoxicity in Mice

Almokhtar A. Adwas1, Abeer A. Elkhoely2, Ahmed M. Kabel3, , Mohamed Nabih Abdel-Rahman3 and Amany A. Eissa2

1Pharmacology department, Faculty of Medicine, Zawia University, Lybia

2Pharmacology and toxicology department, Faculty of Pharmacy, Helwan University, Egypt

3Pharmacology department, Faculty of Medicine, Tanta University, Egypt

Pub. Date: April 20, 2016

Cite this paper:
Almokhtar A. Adwas, Abeer A. Elkhoely, Ahmed M. Kabel, Mohamed Nabih Abdel-Rahman and Amany A. Eissa. Ameliorative Potential of Different Doses of Indol-3-carbinol on Doxorubicin-induced Cardiotoxicity in Mice. Journal of Cancer Research and Treatment. 2016; 4(2):26-31. doi: 10.12691/jcrt-4-2-2

Abstract

Background: Doxorubicin (DOX) is a commonly used chemotherapeutic agent that is associated with serious dose-limiting cardiotoxicity. This cardiotoxicity was attributed to various mechanisms including induction of oxidative stress and inflammation together with inhibition of apoptosis. Indole-3-carbinol (I3C) is a phytochemical that was suggested to have potent anti-oxidant and anti-inflammatory properties. Aim: It was to detect the possible ameliorative effects of different doses of I3C on doxorubicin-induced cardiotoxicity in mice. Methods: Eighty mice were divided into four equal groups: control untreated group; DOX group; DOX + I3C 1000 ppm group and DOX + I3C 2000 ppm group. Survival rate, serum creatine kinase (CK-MB), lactate dehydrogenase (LDH) and troponin I were measured. Also, tissue malondialdehyde (MDA), tissue catalase (CAT), tissue glutathione peroxidase (GPx), and tissue tumor necrosis factor alpha (TNF-α) were determined. Parts of the heart were subjected to histopathological examination. Results: I3C produced dose-dependent significant increase in the survival rate, tissue GPx and CAT with significant decrease in serum CK-MB, LDH, troponin I, tissue MDA and TNF-α and improved the histopathological and immunohistochemical changes compared to DOX-treated group. Conclusion: I3C- in a dose dependent manner- had a protective effect against doxorubicin-induced cardiotoxicity in mice.

Keywords:
indole-3-carbinol doxorubicin cardiotoxicity mice

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References:

[1]  El-Sayyad HI, Ismail MF, Shalaby FM, Abou-El-Magd RF, Gaur RL, Fernando A, et al. Histopathological effects of cisplatin, doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats. Intl J Biol Sci 2009;5(5):466-73.
 
[2]  Al-Harthi SE, Alarabi OM, Ramadan WS, Alaama MN, Al-Kreathy HM, Damanhouri ZA, et al. Amelioration of doxorubicininduced cardiotoxicity by resveratrol. Mol Med Rep 2014; 10: 1455-60.
 
[3]  Kabel AM, Omar MS, Balaha MF, Borg HM. Effect of metformin and adriamycin on transplantable tumor model. Tissue and Cell 2015; 47(5):498-505.
 
[4]  Shi Y, Moon M, Dawood S, McManus B, Liu PP. Mechanisms and management of doxorubicin cardiotoxicity. Herz 2011; 36(4):296-305.
 
[5]  Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol 2012; 52:1213-25.
 
[6]  Zhang Y-W, Shi J, Li Y-J, Wei L. Cardiomyocyte death in doxorubicin-induced cardiotoxicity. Archivum immunologiae et therapiae experimentalis 2009; 57(6):435-45.
 
[7]  Chang HP, Wang ML, Hsu CY, Liu ME, Chan MH, Chen YH. Suppression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes. Int J Obes (Lond) 2011; 35(12):1530-8.
 
[8]  Oculicz M, Hertig I, Chichlowska J. Effects of indole-3-carbinol on metabolic parameters and on lipogenesis and lipolysis in adipocytes. Czech J Anim Sci 2009; 54(4): 182-9.
 
[9]  Chang HP, Wang ML, Chan MH, Chiu YS, Chen YH. Antiobesity activities of indole-3-carbinol in high-fat-diet-induced obese mice. Nutrition 2011; 27(4):463-70.
 
[10]  Deng W, Zong J, Bian Z, Zhou H, Yuan Y, Zhang R, et al. Indole-3 carbinol protects against pressure overload induced cardiac remodeling via activating AMPK-α. Mol Nutr Food Res 2013; 57: 1680-7.
 
[11]  Heijnen BF, Pelkmans LP, Danser AH, Garrelds IM, Mullins JJ, De Mey JG, et al. Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats. J Renin Angiotensin Aldosterone Syst 2014;15(1):69-81.
 
[12]  Van Acker SA, Kramer K, Voest EE, Grimbergen JA, Zhang J, van der Vijgh WJ, et al. Doxorubicin-induced cardiotoxicity monitored by ECG in freely moving mice. A new model to test potential protectors. Cancer Chemother Pharmacol 1996; 38(1):95-101.
 
[13]  Shorey LE, Madeen EP, Atwell LL, Ho E, Löhr CV, Pereira CB, et al. Differential modulation of dibenzo[def,p]chrysene transplacental carcinogenesis: maternal diets rich in indole-3-carbinol versus sulforaphane. Toxicol Appl Pharmacol 2013; 270: 60–9.
 
[14]  Yu Z, Mahadevan B, Löhr CV, Fischer KA, Louderback MA, Krueger SK, et al. Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene. Carcinogenesis 2006; 27 (10): 2116-23.
 
[15]  Hess JW, MacDonald RP, Natho GJ, Murdock KJ. Serum creatine phosphokinase:evaluation of a commercial spectrophotometric method. Clin Chem 1967;13:994e1005.
 
[16]  Buhl SN, Jackson KY. Kinetic method for the determination of serum LDH. Clin Chem 1978; 24:828e32.
 
[17]  Aebi H. Catalase in vitro. In: Packer L, editor: Methods in Enzymology. New York, Academic Press, 1984, pp. 121-6.
 
[18]  Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 34: 271-8.
 
[19]  Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179(4073): 588-90.
 
[20]  Kumar S, Marfatia R, Tannenbaum S, Yang C, Avelar E. Doxorubicin-Induced Cardiomyopathy 17 Years after Chemotherapy. Texas Heart Institute Journal 2012; 39(3):424-7.
 
[21]  Gharanei M, Hussain A, Janneh O, Maddock H. Attenuation of Doxorubicin-Induced Cardiotoxicity by mdivi-1: A Mitochondrial Division/Mitophagy Inhibitor. PLoS ONE 2013; 8(10): e77713.
 
[22]  Koul A, Goyal R, Bharati S. Protective effect of Azadirachta indica a. Juss against doxorubicin-induced cardiac toxicity in tumour bearing mice. Indian J Exp Biol 2014; 52(4):323-31.
 
[23]  Osman AM, Nemnem MM, Abou-Bakr AA, Nassier OA, Khayyal MT. Effect of methimazole treatment on doxorubicin-induced cardiotoxicity in mice. Food Chem Toxicol 2009; 47(10): 2425-30.
 
[24]  Deng W, Zong J, Bian Z, Zhou H, Yuan Y, Zhang R, et al. Indole-3-carbinol protects against pressure overload induced cardiac remodeling via activating AMPK-α. Mol Nutr Food Res 2013; 57(9): 1680-7.
 
[25]  Rogan EG. The Natural Chemopreventive Compound Indole-3-carbinol: State of the Science. In Vivo 2006; 20: 221-8.
 
[26]  Simunek T, Sterba M, Popelova O, Adamcova M, Hrdina R, Gersl V. Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 2009; 61:154-171.
 
[27]  Arnao MB, Sanchez-Bravo J, Acosta M. Indole-3-carbinol as a scavenger of free radicals. Biochemistry and Molecular Biology International 1996; 39(6): 1125-34.
 
[28]  Fares F. The Anti-Carcinogenic Effect of Indole-3-Carbinol and 3, 3'-Diindolylmethane and their Mechanism of Action. Med chem 2014; S1: 002.
 
[29]  Riad A, Bien S, Westermann D, Becher PM, Loya K, Landmesser U, et al. Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice. Cancer Res 2009; 69(2):695-9.
 
[30]  Oliveira MS, Melo MB, Carvalho JL, Melo IM, Lavor MS, Gomes DA, et al. Doxorubicin Cardiotoxicity and Cardiac Function Improvement After Stem Cell Therapy Diagnosed by Strain Echocardiography. J Cancer Sci Ther 2013; 5(2):52-7.
 
[31]  Tsai JT, Liu HC, Chen YH. Suppression of inflammatory mediators by cruciferous vegetable-derived indole-3-carbinol and phenylethyl isothiocyanate in lipopolysaccharide-activated macrophages. Mediators Inflamm 2010; 2010:293642.
 
[32]  Elmore S. Apoptosis: A Review of Programmed Cell Death. Toxicologic pathology 2007; 35(4):495-516.
 
[33]  Thandavarayan RA, Giridharan VV, Arumugam S, Suzuki K, Ko KM, Krishnamurthy P, et al. Schisandrin B Prevents Doxorubicin Induced Cardiac Dysfunction by Modulation of DNA Damage, Oxidative Stress and Inflammation through Inhibition of MAPK/p53 Signaling. Tang Y, ed. PLoS ONE 2015; 10(3):e0119214.
 
[34]  Choi HS, Cho MC, Lee HG, Yoon DY. Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells. Food Chem Toxicol 2010; 48(3):883-90.
 
[35]  Rahman KM, Li Y, Sarkar FH. Inactivation of akt and NF-kappa B play important roles during indole-3-carbinol-induced apoptosis in breast cancer cells. Nutr Cancer 2004; 48(1):84-94.