The protective effects of curcumin and curmumin nanomicelle against cirrhotic cardiomyopathy in bile duct-ligated rats

Document Type : Research Paper

Authors

1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pharmaceutics, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Cirrhotic cardiomyopathy refers to cardiac muscle dysfunction caused by liver cirrhosis. Seemingly, free radicals and inflammatory factors play a critical role in the pathophysiology of cardiomyopathy. Curcumin has the anti-inflammatory, antioxidant, and anticancer properties . However, the therapeutic indications of this compound are limited due to its low absorption, rapid metabolism, and low bioavailability. Curcumin nanomicelle is a form of nanoparticle developed to overcome the poor kinetic profile of curcumin and enhance its bioavailability and therapeutic effects. The present study aimed to develop an experimental model of cirrhosis induced by biliary duct ligation in rats.
Materials and Methods: The animals were kept until 28 days after the bile duct ligation and received curcumin or curcumin nanomicelle via oral gavage at various doses during days 7-28. After the intervention, the effects of curcumin and curcumin nanomicelle on cardiovascular function, some inflammatory and antioxidant biomarkers, and histopathological changes were assessed.
Results: According to the findings, cardiac electrophysiology function and contractile force improved only in the curcumin nanomicelle groups. In addition, curcumin nanomicelle significantly reduced inflammatory factors and increased antioxidant enzymes. In the histopathological studies, cardiac tissue damage and destruction were observed to decrease in the curcumin nanomicelle groups.
Conclusion: Therefore, it was concluded that curcumin nanomicelle plays a protective role in cirrhotic cardiomyopathy by reducing inflammatory and oxidative factors and improving the cardiac function. Furthermore, curcumin nanomicelle exhibited more significant therapeutic effects compared to the curcumin treatment groups.

Keywords


1.Davies M. The cardiomyopathies: an overview. Heart. 2000; 83(4): 469-674.
2.Wexler R, Elton T, Pleister A, Feldman D. Cardiomyopathy: an overview. Am Fam Physician. 2009; 79(9): 778-784.
3.Wong F. Cirrhotic cardiomyopathy. Hepatol Int. 2009; 3(1): 294-304.
4.Møller S, Lee SS. Cirrhotic cardiomyopathy. J Hepatol. 2018; 69(4): 958--960.
5.Møller S, Bernardi M. Interactions of the heart and the liver. Eur Heart J. 2013; 34(36): 2804-2811.
6.Regan TJ, Levinson GE, Oldewurtel HA, Frank MJ, Weisse AB, Moschos CB. Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy. J Clin Invest. 1969; 48(2): 397-407.
7.Ingles AC, Hernandez I, Garcia-Estan J, Quesada T, Carbonell LF. Limited cardiac preload reserve in conscious cirrhotic rats. Am J Physiol Heart Circ Physiol. 1991; 260(6): H1912-H7.
8.Pacher P, Bátkai S, Kunos G. Cirrhotic cardiomyopathy: an endocannabinoid connection? Br J Pharmacol. 2005; 146(3): 313-314.
9.Chayanupatkul M, Liangpunsakul S. Cirrhotic cardiomyopathy: review of pathophysiology and treatment. Hepatol Int. 2014; 8(3): 308-315.
10.Liu H, Song D, Lee SS. Cirrhotic cardiomyopathy. Gastroenterol Clin Biol. 2002; 26: 842–847.
11.Gaskari SA, Honar H, Lee SS. Therapy insight: cirrhotic cardiomyopathy. Nat Clin Pract Gastroenterol Hepatol. 2006; 3(6): 329-337.
12.van Obbergh L, Vallieres Y, Blaise G. Cardiac modifications occurring in the ascitic rat with biliary cirrhosis are nitric oxide related. J Hepatol. 1996; 24(6):747-452.
13.Ward CA, Liu H, Lee SS. Altered cellular calcium regulatory systems in a rat model of cirrhotic cardiomyopathy. Gastroenterology. 2001; 121(5):1209-218.
14.Kountouras J, Billing BH, Scheuer PJ. Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat. Br J Exp Pathol. 1984; 65(3): 305-311.
15.Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). Int J Complement Altern Med. 2003; 9(1): 161-168.
16.Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta medica. 1991; 57(01): 1-7.
17.Nisenberg O. Targeted Overexpression of S-adenosylmethionine Decarboxylase in Murine Hearts. 2003.
18.Foti MC. Antioxidant properties of phenols. J Pharm Pharmacol. 2007; 59(12): 1673-1685.
19.Kapakos G, Youreva V, Srivastava AK. Cardiovascular protection by curcumin: molecular aspects. Indian J Biochem Biophys. 2012; 49(5): 306-315.
20.Yu W, Wu J, Cai F, Xiang J, Zha W, Fan D. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLoS One. 2012; 7(12): e52013.
21.Hewlings SJ, Kalman DS. Curcumin: a review of its’ effects on human health. Foods. 2017; 22; 6(10). pii: E92.
22.Lavan DA, McGuire T, Langer R. Small-scale systems for in vivo drug delivery. Nat. Biotechnol. 2003; 21(10): 1184-1191.
23.Cavalcanti A, Shirinzadeh B, Freitas Jr RA, Hogg T. Nanorobot architecture for medical target identification. Nanotechnology. 2007; 19(1): 015103.
24.Mitra AK, Cholkar K, Mandal A. Emerging nanotechnologies for diagnostics, drug delivery and medical devices: William Andrew; 2017.
25.Rezayat S. The protective effect of nano-curcumin in experimental model of acute pancreatitis: The involvement of TLR4/NF-kB pathway. Nanomed J. 2018; 5(3): 138-143.
26.Dolati S, Ahmadi M, Aghebti-Maleki L, Nikmaram A, Marofi F, Rikhtegar R. Nanocurcumin is a potential novel therapy for multiple sclerosis by influencing inflammatory mediators. Pharmacol Rep. 2018; 70(6): 1158-1167.
27.Tarcin O, Basaranoglu M, Tahan V, Tahan G, Sücüllü I, Yilmaz N. Time course of collagen peak in bile duct-ligated rats. BMC Gastroenterol. 2011;11(1): 45.
28.Mani AR, Ippolito S, Ollosson R, Moore KP. Nitration of cardiac proteins is associated with abnormal cardiac chronotropic responses in rats with biliary cirrhosis. Hepatology. 2006; 43(4): 847-856.
29.Garrido M, Escobar C, Zamora C, Rejas C, Varas J, Párraga M, et al. Bile duct ligature in young rats: A revisited animal model for biliary atresia. Eur J Histochem. 2017; 61(3): 2803.
30.Yang Y, Chen B, Chen Y, Zu B, Yi B, Lu K. A comparison of two common bile duct ligation methods to establish hepatopulmonary syndrome animal models. Lab Anim. 2015; 49(1): 71-79.
31.Gaskari SA, Liu H, Moezi L, Li Y, Baik SK, Lee SS. Role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy in bile duct‐ligated rats. Br J Pharmacol. 2005; 146(3): 315-323.
32.Bruck R, Ashkenazi M, Weiss S, Goldiner I, Shapiro H, Aeed H. Prevention of liver cirrhosis in rats by curcumin. Liver Int. 2007; 27(3): 373-383.
33.Li L, Duan M, Chen W, Jiang A, Li X, Yang J, et al. The spleen in liver cirrhosis: revisiting an old enemy with novel targets. J Transl Med. 2017; 15(1): 111.
34.Moore K, Roberts LJ. Measurement of lipid peroxidation. Free Radic Res. 1998; 28(6): 659-671.
35.Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2): 351-358.
36.Ighodaro O, Akinloye O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex J Med. 2018; 54(4): 287-293.
37.Haq MM, Legha SS, Choksi J, Hortobagyi GN, Benjamin RS, Ewer M. Doxorubicin‐induced congestive heart failure in adults. Cancer. 1985; 56(6): 1361-1365.
38.Yarmohmmadi F, Rahimi N, Faghir-Ghanesefat H, Javadian N, Abdollahi A, Pasalar P. Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat. Eur J Pharmacol. 2017; 796: 39-44.
39.Sheibani M, Nezamoleslami S, Faghir-Ghanesefat H, hossein Emami A, Dehpour AR. Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats. Cancer Chemother Pharmacol. 2020:1-9.
40.Radu R, Bold A, Pop O, Mălăescu D, Gheorghişor I, Mogoantă L. Histological and immunohistochemical changes of the myocardium in dilated cardiomyopathy. Rom J Morphol Embryol. 2012; 53(2): 269-275.
41.Timoh T, Protano M, Wagman G, Bloom M, Vittorio T, editors. A perspective on cirrhotic cardiomyopathy. Transplantation proceedings; 2011: Elsevier.
42.Gassanov N, Caglayan E, Semmo N, Massenkeil G, Er F. Cirrhotic cardiomyopathy: a cardiologist’s perspective. World J Gastroenterol. 2014; 20(42): 15492-15498.
43.Møller S, Hove JD, Dixen U, Bendtsen F. New insights into cirrhotic cardiomyopathy. Int J Cardiol. 2013; 167(4): 1101-1108.
44.Liu H, Lee SS. Nuclear factor‐κB inhibition improves myocardial contractility in rats with cirrhotic cardiomyopathy. Liver Int. 2008; 28(5): 640-648.
45.Sánchez-Fidalgo S, Cárdeno A, Villegas I, Talero E, de la Lastra CA. Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. Eur J Pharmacol. 2010; 633(1-3): 78-84.
46.Bereswill S, Muñoz M, Fischer A, Plickert R, Haag L-M, Otto B, et al. Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation. PloS one. 2010; 3;5(12): e15099..
47.Mošovská S, Petáková P, Kaliňák M, Mikulajová A. Antioxidant properties of curcuminoids isolated from Curcuma longa L. Acta Chimica Slovaca. 2016; 9(2): 130-135.
48.Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. The molecular targets and therapeutic uses of curcumin in health and disease: Springer; 2007. p. 105-125.
49.Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Alternative medicine review. 2009; 14(2).
50.Hatamipour M, Sahebkar A, Alavizadeh SH, Dorri M, Jaafari MR. Novel nanomicelle formulation to enhance bioavailability and stability of curcuminoids. Iran J Basic Med Sci. 2019; 22(3): 282-289.
51.Javadi M, Khadem Haghighian H, Goodarzy S, Abbasi M, Nassiri‐Asl M. Effect of curcumin nanomicelle on the clinical symptoms of patients with rheumatoid arthritis: A randomized, double‐blind, controlled trial. Int J Rheum Dis. 2019; 22(10): 1857-1862.
52.Sundar Dhilip Kumar S, Houreld NN, Abrahamse H. Therapeutic potential and recent advances of curcumin in the treatment of aging-associated diseases. Molecules. 2018; 23(4): 835.
53.Rahimi HR, Nedaeinia R, Shamloo AS, Nikdoust S, Oskuee RK. Novel delivery system for natural products: Nano-curcumin formulations. Avicenna J Phytomed. 2016 Jul-Aug; 6(4): 383-398.
54.Fourlas CA, Alexopoulou AA. Cirrhotic cardiomyopathy. Hellenic J Cardiol. 2004; 45:114-120.
55.Karagiannakis DS, Vlachogiannakos J, Anastasiadis G, Vafiadis-Zouboulis I, Ladas SD. Frequency and severity of cirrhotic cardiomyopathy and its possible relationship with bacterial endotoxemia. Dig Dis Sci. 2013; 58(10): 3029-3036.
56.Behrendt P, Preusse-Prange A, Klüter T, Haake M, Rolauffs B, Grodzinsky A. IL-10 reduces apoptosis and extracellular matrix degradation after injurious compression of mature articular cartilage. Osteoarthritis Cartilage. 2016; 24(11): 1981-1988.
57.Hofstetter C, Flondor M, Hoegl S, Muhl H, Zwissler B. Interleukin-10 aerosol reduces proinflammatory mediators in bronchoalveolar fluid of endotoxemic rat. Crit Care Med. 2005; 33(10): 2317-2322.
58.Hellenbrand DJ, Reichl KA, Travis BJ, Filipp ME, Khalil AS, Pulito DJ. Sustained interleukin-10 delivery reduces inflammation and improves motor function after spinal cord injury. J Neuroinflammation. 2019; 16(1): 93.
59.Khan J, Noboru N, Young A, Thomas D. Pro and anti-inflammatory cytokine levels (TNF-α, IL-1β, IL-6 and IL-10) in rat model of neuroma. Pathophysiology. 2017; 24(3): 155-159.
60.Mu W, Ouyang X, Agarwal A, Zhang L, Long DA, Cruz PE, et al. IL-10 suppresses chemokines, inflammation, and fibrosis in a model of chronic renal disease. J Am Soc Nephrol. 2005; 16(12): 3651-3660.
61.Amirshahrokhi K, Ghazi-Khansari M, Mohammadi-Farani A, Karimian G. Effect of captopril on TNF-α and IL-10 in the livers of bile duct ligated rats. Iranian J Immunol. 2010; 7(4): 247-251.
62.Niki E. Lipid peroxidation products as oxidative stress biomarkers. Biofactors. 2008; 34(2): 171-180.
63.Gaweł S, Wardas M, Niedworok E, Wardas P. Malondialdehyde (MDA) as a lipid peroxidation marker. Wiadomosci lekarskie (Warsaw, Poland: 1960). 2004; 57(9-10): 453-455.
64.Wolf G. The discovery of the antioxidant function of vitamin E: the contribution of Henry A. Mattill. J Nutr. 2005; 135(3): 363-366.
65.Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy reviews. 2010; 4(8): 118.
66.Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, Sánchez-Pérez P, Cadenas S, et al. Antioxidant responses and cellular adjustments to oxidative stress. Redox biology. 2015; 6: 183-197.
67.Hwang C, Sinskey AJ, Lodish HF. Oxidized redox state of glutathione in the endoplasmic reticulum. Science. 1992; 257(5076): 1496-502.
68.Wang X-L, Li T, Li J-H, Miao S-Y, Xiao X-Z. The effects of resveratrol on inflammation and oxidative stress in a rat model of chronic obstructive pulmonary disease. Molecules. 2017; 22(9): 1529.
69.Lebovitz RM, Zhang H, Vogel H, Cartwright J, Dionne L, Lu N. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proceedings of the National Academy of Sciences. 1996; 93(18): 9782-9787.