سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Bayat, Gholamreza, Hashemi, Seyed Ali, Karim, Hosein, Fallah, Parviz, Hedayatyanfard, Keshvad, Bayat, Mahnaz, Khalili, Azadeh. (1400). Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3. , 25(1), 126-133. doi: 10.22038/ijbms.2022.60888.13485
Gholamreza Bayat; Seyed Ali Hashemi; Hosein Karim; Parviz Fallah; Keshvad Hedayatyanfard; Mahnaz Bayat; Azadeh Khalili. "Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3". , 25, 1, 1400, 126-133. doi: 10.22038/ijbms.2022.60888.13485
Bayat, Gholamreza, Hashemi, Seyed Ali, Karim, Hosein, Fallah, Parviz, Hedayatyanfard, Keshvad, Bayat, Mahnaz, Khalili, Azadeh. (1400). 'Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3', , 25(1), pp. 126-133. doi: 10.22038/ijbms.2022.60888.13485
Bayat, Gholamreza, Hashemi, Seyed Ali, Karim, Hosein, Fallah, Parviz, Hedayatyanfard, Keshvad, Bayat, Mahnaz, Khalili, Azadeh. Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3. , 1400; 25(1): 126-133. doi: 10.22038/ijbms.2022.60888.13485

Biliary cirrhosis-induced cardiac abnormality in rats: Interaction between Farnesoid-X-activated receptors and the cardiac uncoupling proteins 2 and 3

Iranian Journal of Basic Medical Sciences
مقاله 17، دوره 25، شماره 1، فروردین 2022، صفحه 126-133    اصل مقاله (841.9 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2022.60888.13485
نویسندگان
Gholamreza Bayat1، 2؛ Seyed Ali Hashemi3؛ Hosein Karim4، 5؛ Parviz Fallah6؛ Keshvad Hedayatyanfard1، 4؛ Mahnaz Bayat7؛ Azadeh Khalili* 1، 4
1Department of Physiology-Pharmacology-Medical Physic, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
2Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
3Department of Pathology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
4Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
5Department of Cardiology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
6Department of Medical Laboratory Sciences, Faculty of Para-Medicine, Alborz University of Medical Sciences, Karaj, Iran
7Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
چکیده
Objective(s): This study aimed to evaluate the relationship between Farnesoid-X-activated receptors (FXR) as nuclear regulators of the antioxidant defense system as well as cardiac mitochondrial carrier proteins of UCP2 and UCP3 in cardiac damage induced by cirrhosis. 
Materials and Methods: Twenty-two male Wistar rats (200–250 g) were randomly divided into 3 experimental groups, including a control group (n=6), a sham-operated group (n=8), and a bile duct ligated (BDL) group (n=8). Four weeks after surgical intervention, biochemical assessment (AST, ALT, GGT, LDH, and ALP), histological observation, and molecular evaluation (FXR, UCP2, UCP3, BNP, Caspase3, and GAPDH) using real-time RT-PCR were performed. 
Results: Compared with the sham-operation group, the BDL group showed a significant rise in liver enzymes of AST, ALT, GGT, LDH, and ALP. Defined fibrotic and necrotic bundles and thick reticulin fibers were also found in BDL liver tissue. Besides liver morphological alterations, left ventricles of BDL ones were also associated with defined cardiomyocyte hypertrophy, myofiber vacuolization, and clear pigmentation. Findings showed a significant up-regulation of cardiac Brain Natriuretic Peptide (BNP) along with marked down-regulation in hepatic FXR, cardiac FXR, and cardiac UCP2 and UCP3. However, the expression of caspase 3 in the cardiac tissue was not affected by BDL operation during 4 weeks. 
Conclusion: Expression of FXR as an upstream regulator of cellular redox status, besides the non-enzymatic ROS buffering defense system of cardiac UCPs, has a pivotal role in the pathogenesis of cirrhotic-induced cardiac abnormality in rats.
کلیدواژه‌ها
Cardiomyopathy؛ Cholestasis؛ Farnesoid-X-receptor؛ Liver cirrhosis؛ Mitochondrial uncoupling proteins
مراجع
1. Caramelo C Fau - Fernandez-Muñoz D, Fernandez-Muñoz D Fau - Santos JC, Santos Jc Fau - Blanchart A, Blanchart A Fau - Rodriguez-Puyol D, Rodriguez-Puyol D Fau - López-Novoa JM, López-Novoa Jm Fau - Hernando L, et al. Effect of volume expansion on hemodynamics, capillary permeability and renal function in conscious, cirrhotic rats. Hepatology 1986; 6:129-134.
2. Cazzaniga M, Salerno F, Pagnozzi G, Dionigi E, Visentin S, Cirello I, et al. Diastolic dysfunction is associated with poor survival in patients with cirrhosis with transjugular intrahepatic portosystemic shunt. Gut 2007; 56:869-875.
3. Carvalho MVH, Kroll PC, Kroll RTM, Carvalho VN. Cirrhotic cardiomyopathy: the liver affects the heart. Braz J Med Biol Res 2019; 52:e7809.
4. Cichoż-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol 2014; 20:8082-8091.
5. Orr AL, Ashok D, Sarantos MR, Shi T, Hughes RE, Brand MD. Inhibitors of ROS production by the ubiquinone-binding site of mitochondrial complex I identified by chemical screening. Free Radic Biol Med 2013; 65:1047-1059.
6. Meany DL, Poe BG, Navratil M, Moraes CT, Arriaga EA. Superoxide released into the mitochondrial matrix. Free Radic Biol Med 2006; 41:950-959.
7. Mousavi K, Niknahad H, Ghalamfarsa A, Mohammadi H, Azarpira N, Ommati MM, et al. Taurine mitigates cirrhosis-associated heart injury through mitochondrial-dependent and antioxidative mechanisms. Clin Exp Hepatol 2020; 6:207-219.
8. Safari F, Anvari Z, Moshtaghioun S, Javan M, Bayat G, Forosh SS, et al. Differential expression of cardiac uncoupling proteins 2 and 3 in response to myocardial ischemia-reperfusion in rats. Life Sci 2014; 98:68-74.
9. Chen GG, Yan JB, Wang XM, Zheng MZ, Jiang JP, Zhou XM, et al. Mechanism of uncoupling protein 2‑mediated myocardial injury in hypothermic preserved rat hearts. Mol Med Rep 2016; 14:1857-1864.
10. Bugger H, Guzman C, Zechner C, Palmeri M, Russell KS, Russell RR, 3rd. Uncoupling protein down-regulation in doxorubicin-induced heart failure improves mitochondrial coupling but increases reactive oxygen species generation. Cancer Chemother Pharmacol 2011; 67:1381-1388.
11. Hoerter J, Gonzalez-Barroso MD, Couplan E, Mateo P, Gelly C, Cassard-Doulcier AM, et al. Mitochondrial uncoupling protein 1 expressed in the heart of transgenic mice protects against ischemic-reperfusion damage. Circulation 2004; 110:528-533.
12. Teshima Y, Akao M, Jones Steven P, Marbán E. Uncoupling Protein-2 Overexpression Inhibits Mitochondrial Death Pathway in Cardiomyocytes. Circ Res 2003; 93:192-200.
13. Gai Z, Chu L, Xu Z, Song X, Sun D, Kullak-Ublick GA. Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage. Sci Rep 2017; 7:9815.
14. Haga S, Yimin, Ozaki M. Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis. BMC Gastroenterol 2017; 17:9-21.
15. Zhang Y, Xu Y, Qi Y, Xu L, Song S, Yin L, et al. Protective effects of dioscin against doxorubicin-induced nephrotoxicity via adjusting FXR-mediated oxidative stress and inflammation. Toxicology 2017; 378:53-64.
16. Gai Z, Gui T, Hiller C, Kullak-Ublick GA. Farnesoid X Receptor Protects against Kidney Injury in Uninephrectomized Obese Mice. J Biol Chem 2016; 291:2397-2411.
17. Lu C, Zhang F, Xu W, Wu X, Lian N, Jin H, et al. Curcumin attenuates ethanol-induced hepatic steatosis through modulating Nrf2/FXR signaling in hepatocytes. IUBMB Life 2015; 67:645-658.
18. Xia Y, Zhang F, Zhao S, Li Y, Chen X, Gao E, et al. Adiponectin determines farnesoid X receptor agonism-mediated cardioprotection against post-infarction remodelling and dysfunction. Cardiovasc Res 2018; 114:1335-1349.
19. Wu H, Liu G, He Y, Da J, Xie B. Obeticholic acid protects against diabetic cardiomyopathy by activation of FXR/Nrf2 signaling in db/db mice. Eur J Pharmaco 2019; 858:172393.
20. Gao J, Liu X, Wang B, Xu H, Xia Q, Lu T, et al. Farnesoid X receptor deletion improves cardiac function, structure and remodeling following myocardial infarction in mice. Mol Med Rep 2017; 16:673-679.
21. Han CY, Kim TH, Koo JH, Kim SG. Farnesoid X receptor as a regulator of fuel consumption and mitochondrial function. Arch Pharm Res 2016; 39:1062-1074.
22. 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; 49:71-79.
23. Khalili A, Fallah P, Hashemi SA, Ahmadian-Attari MM, Jamshidi V, Mazloom R, et al. New mechanistic insights into hepatoprotective activity of milk thistle and chicory quantified extract: The role of hepatic Farnesoid-X activated receptors. Avicenna J Phytomed 2021; 11:367-379.
24. Safari F, Hajiadeh S, Moshtaghion SH, Forouzandeh Moghadam M, Shekarforoush S, Bayat G, et al. Effect of losartan on NOX2 transcription following acute myocardial ischemia-reperfusion. Physiol-Pharmacol 2012; 16:44-53.
25. Desai MS, Mathur B, Eblimit Z, Vasquez H, Taegtmeyer H, Karpen SJ, et al. Bile acid excess induces cardiomyopathy and metabolic dysfunctions in the heart. Hepatology 2017; 65:189-201.
26. Jazaeri F, Afsharmoghaddam R, Abdollahi A, Ghamami G, Dehpour AR. Evaluation of chronic losartan treatment effect on cardiac chronotropic dysfunction in biliary cirrhotic rats. Acta Med Iran 2018; 56:4-13.
27. Cruz A, Tasset I, Ramírez LM, Arjona A, Segura J, Túnez I, et al. Effect of melatonin on myocardial oxidative stress induced by experimental obstructive jaundice. Rev Esp Enferm Dig 2009; 101:460-463.
28. Matyas C, Erdelyi K, Trojnar E, Zhao S, Varga ZV, Paloczi J, et al. Interplay of Liver–Heart Inflammatory Axis and Cannabinoid 2 Receptor Signaling in an Experimental Model of Hepatic Cardiomyopathy. Hepatology 2020; 71:1391-1407.
29. Kemp R, Castro-e-Silva O, Santos JS, Sankarankutty AK, Correa RB, Baldo CF, et al. Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction. Acta Cir Bras 2008; 23:66-71.
30. Lunseth JH, Olmstead EG, Abboud F. A study of heart disease in one hundred eight hospitalized patients dying with portal cirrhosis. AMA Arch Intern Med 1958; 102:405-413.
31. Chayanupatkul M, Liangpunsakul S. Cirrhotic cardiomyopathy: review of pathophysiology and treatment. Hepatol Int 2014; 8:308-315.
32. Sergeeva IA, Christoffels VM. Regulation of expression of atrial and brain natriuretic peptide, biomarkers for heart development and disease. Biochim Biophys Acta 2013; 1832:2403-2413.
33. Nunes S, Soares E, Fernandes J, Viana S, Carvalho E, Pereira FC, et al. Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker. Cardiovasc Diabetol 2013; 12:44-54.
34. Januzzi JL, Jr. Natriuretic peptides as biomarkers in heart failure. J Investig Med 2013; 61:950-955.
35. Duran J, Martinez A, Adler E. Cardiovascular Manifestations of Mitochondrial Disease. Biology (Basel) 2019; 8:34-60.
36. Hilse KE, Rupprecht A, Egerbacher M, Bardakji S, Zimmermann L, Wulczyn AEMS, et al. The expression of uncoupling protein 3 coincides with the fatty acid oxidation type of metabolism in adult murine heart. Front Physiol 2018; 9:747.
37. Duncan JG. Mitochondrial dysfunction in diabetic cardiomyopathy. Biochim Biophys Acta 2011; 1813:1351-1359.
38. Ramachandra CJA, Hernandez-Resendiz S, Crespo-Avilan GE, Lin Y-H, Hausenloy DJ. Mitochondria in acute myocardial infarction and cardioprotection. EBioMedicine 2020; 57:102884.
39. Bugger H, Abel ED. Mitochondria in the diabetic heart. Cardiovasc Res 2010; 88:229-240.
40. Hassanein T. Mitochondrial dysfunction in liver disease and organ transplantation. Mitochondrion 2004; 4:609-620.
41. Viengchareun S, Penfornis P, Zennaro M-C, Lombès M. Mineralocorticoid and glucocorticoid receptors inhibit UCP expression and function in brown adipocytes. Am J Physiol Endocrinol Metab 2001; 280:E640-E649.
42. Perrino C, Schiattarella GG, Sannino A, Pironti G, Petretta MP, Cannavo A, et al. Genetic deletion of uncoupling protein 3 exaggerates apoptotic cell death in the ischemic heart leading to heart failure. J Am Heart Assoc 2013; 2:e000086.
43. Harmancey R, Vasquez HG, Guthrie PH, Taegtmeyer H. Decreased long-chain fatty acid oxidation impairs postischemic recovery of the insulin-resistant rat heart. FASEB J 2013; 27:3966-3978.
44. Verbeke L, Mannaerts I, Schierwagen R, Govaere O, Klein S, Vander Elst I, et al. FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis. Sci Rep 2016; 6-Last page.
45. Wu W, Zhu B, Peng X, Zhou M, Jia D, Gu J. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease. Biochem Biophys Res Commun 2014; 443:68-73.
46. Lívero FA, Stolf AM, Dreifuss AA, Bastos-Pereira AL, Chicorski R, de Oliveira LG, et al. The FXR agonist 6ECDCA reduces hepatic steatosis and oxidative stress induced by ethanol and low-protein diet in mice. Chem Biol Interact 2014; 217:19-27.
47. Wang B, Zhang H, Luan Z, Xu H, Wei Y, Zhao X, et al. Farnesoid X receptor (FXR) activation induces the antioxidant protein metallothionein 1 expression in mouse liver. Exp Cell Res 2020; 390:111949.
48. Qiang S, Tao L, Zhou J, Wang Q, Wang K, Lu M, et al. Knockout of farnesoid X receptor aggravates process of diabetic cardiomyopathy. Diabetes Res Clin Pract 2020; 161:108033.
49. Pu J, Yuan A, Shan P, Gao E, Wang X, Wang Y, et al. Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury. Eur Heart J 2013; 34:1834-1845.
50. Tsoporis James N, Izhar S, Desjardins Jean F, Salpeas V, Rizos Ioannis C, Parker Thomas G. Abstract 16846: Activation of farnesoid x receptor signaling mediates atrial myocyte apoptosis in patients undergoing on-pump coronary artery bypass grafting and ventricular remodeling after experimental myocardial infarction. Circulation 2017; 136:A16846-A16846.

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