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Yıl 2022, Cilt: 26 Sayı: 6, 1893 - 1899, 28.06.2025

Merve Arici , Tugce Boran , Gül Özhan

https://doi.org/10.29228/jrp.279

Öz

Kaynakça

  • [1] Richette P, Bardin T. Gout. Lancet. 2010; 375(9711): 318-28. [CrossRef]
  • [2] Choi HK, Gout B. Epidemiology, pathology, and pathogenesis. Primer on the rheumatic diseases. 13th ed. Atlanta, GA: Arthritis Foundation, 2008; 250-256. [CrossRef]
  • [3] Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V. Regulation of uric acid metabolism and excretion. Int J Cardiol. 2016; 213: 8-14. [CrossRef]
  • [4] Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, Kaldas M et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012; 64(10): 1431-1446. [CrossRef]
  • [5] FDA. 2015. HIGHLIGHTS OF PRESCRIBING INFORMATION – ZURAMPIC https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf (accessed July 24, 2020)
  • [6] EMA 2016. ZURAMPIC. https://www.ema.europa.eu/en/documents/overview/zurampic-epar-summarypublic_en.pdf (accessed July 25 2020)
  • [7] Bardin T, Keenan RT, Khanna PP, Kopicko J, Fung M, Bhakta N, Adler S, Storgard C, Baumgartner S, So A. Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann Rheum Dis, 2017; 76(5): 811-820. [CrossRef]
  • [8] Dalbeth N, Jones G, Terkeltaub R, Khanna D, Kopicko J, Bhakta N, Adler S, Fung M, Storgard C, Baumgartner S, Perez‐Ruiz F. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with febuxostat in patients with tophaceous gout: findings of a phase III clinical trial. Arthritis Rheumatol. 2017; 69(9): 1903-1913. [CrossRef]
  • [9] Saag KG, Fitz‐Patrick D, Kopicko J, Fung M, Bhakta N, Adler S, Storgard C, Baumgartner S, Becker MA. Lesinurad combined with allopurinol: a randomized, double‐blind, placebo‐controlled study in gout patients with an inadequate response to standard‐of‐care allopurinol (a US‐based study). Arthritis Rheumatol. 2017; 69(1): 203-212. [CrossRef]
  • [10] Daubney J, Bonner PL, Hargreaves AJ, Dickenson JM. Cardioprotective and cardiotoxic effects of quercetin and two of its in vivo metabolites on differentiated H9c2 cardiomyocytes. Basic Clin Pharmacol Toxicol. 2015; 116(2): 96-109. [CrossRef]
  • [11] Gill C, Mestril R, Samali A. Losing heart: the role of apoptosis in heart disease-A novel therapeutic target? The FASEB J. 2002; 16(2): 135-146. [CrossRef]
  • [12] Perik PJ, de Vries EGE, Gietema JA, van der Graaf WTA, Sleijfer DT, Suurmeijer AJH, van Veldhuisen DJ. The dilemma of the strive for apoptosis in oncology: mind the heart. Crit Rev Oncol Hematol. 2005; 53(2): 101-113. [CrossRef]
  • [13] Foo RSY, Mani K, Kitsis RN. Death begets failure in the heart. The Journal of Clinical Investigation. 2005; 115(3): 565-571. [CrossRef]
  • [14] Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Loreto CD, Beltrami CA, Krajewski S, Reed JC. Apoptosis in the failing human heart. NEJM. 1997; 336(16): 1131-1141. [CrossRef]
  • [15] Bernuzzi F, Recalcati S, Alberghini A, Cairo G. Reactive oxygen species-independent apoptosis in doxorubicin-treated H9c2 cardiomyocytes: role for heme oxygenase-1 down-modulation. Chem Biol Interact. 2009; 177(1): 12-20. [CrossRef]
  • [16] Li S, Wang W, Niu T, Wang H, Li B, Shao L, Lai Y, Li H, Janicki JS, Wang XL, Tang D, Cui T. Nrf2 deficiency exaggerates doxorubicin-induced cardiotoxicity and cardiac dysfunction. Oxid Med Cell Longev. 2014; 2014: 748524. [CrossRef]
  • [17] Ghyasi R, Sepehri G, Mohammadi M, Badalzadeh R, Ghyasi A. Effect of mebudipine on oxidative stress and lipid peroxidation in myocardial ischemic-reperfusion injury in male rat. J Res Med Sci: The Official Journal of Isfahan University of Medical Sciences. 2012; 17(12): 1150. [CrossRef]
  • [18] Menazza S, Canton M, Sorato E, Boengler K, Schulz R, Di Lisa F. Old and new biomarkers of oxidative stress in heart failure. Drug Discov Today Ther Strateg. 2012; 9(4): e189-e198. [CrossRef]
  • [19] Costa VM, Carvalho F, Duarte JA, Bastos MDL, Remião F. The heart as a target for xenobiotic toxicity: the cardiac susceptibility to oxidative stress. Chem Res Toxicol. 2013; 26(9): 1285-1311. [CrossRef]
  • [20] Franco R, Cidlowski JA. Glutathione efflux and cell death. Antioxidants and Redox Signalling. 2012; 17(12): 1694-1713. [CrossRef]
  • [21] Sharma S, Jackson PG, Makan J. Cardiac troponins. J Clin Pathol. 2004; 57: 1025-1026. [CrossRef]
  • [22] Panteghini M, Apple FS, Christenson RH, Dati F, Mair J, Wu AH. Proposals from IFCC Committee on standardization of markers of cardiac damage (C-SMCD): recommendations on use of biochemical markers of cardiac damage in acute coronary syndromes. Scand J Clin Lab. 1999; 59(230): 103-112. [CrossRef]
  • [23] Adamcova M, Šterba M, Šimunek T, Potacova A, Popelova O, Mazurova Y, Geršl V. Troponin as a marker of myocardiac damage in drug-induced cardiotoxicity. Expert Opin Drug Saf. 2005; 4(3): 457-472. [CrossRef]
  • [24] Jankowski M, Bissonauth V, Gao L, Gangal M, Wang D, Danalache B, Wang Y, Stoyanova E, Cloutier G, Blaise G, Gutkowska J. Anti-inflammatory effect of oxytocin in rat myocardial infarction. Basic Res Cardiol. 2010; 105: 205-218. [CrossRef]
  • [25] Sehnert AJ, Huq A, Weinstein BM, Walker C, Fishman M, Stainier DY. Cardiac troponin T is essential in sarcomere assembly and cardiac contractility. Nat Genet. 2002; 31: 106-110. [CrossRef]
  • [26] Zhang Q, Li J, Peng S, Zhang Y, Qiao Y. Rosmarinic acid as a candidate in a phenotypic profiling cardio-/cytotoxicity cell model induced by doxorubicin. Molecules. 2020; 25(4): 836. [CrossRef]
  • [27] Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72(1-2): 248-254. [CrossRef]

Evaluation of lesinurad-induced cardiotoxicity in cardiomyoblastic cells

Yıl 2022, Cilt: 26 Sayı: 6, 1893 - 1899, 28.06.2025

Merve Arici , Tugce Boran , Gül Özhan

https://doi.org/10.29228/jrp.279

Öz

Lesinurad, a uric acid transporter-1 (URAT1) inhibitor, is a uricosuric medicine and administered in combination therapy with a xanthine oxidase inhibitör (XOI) when the targeted serum uric acid level with XOIs cannot be reached in the treatment of gout. The cardiovascular adverse effects related to the use of lesinurad have been reported by authorities, but the underlying causes have not been elucidated yet. Therefore, to investigate the cardiotoxic potential and its mechanisms, oxidative stress, apoptosis, and troponin I/T protein expressions that are important in cardiac functions were evaluated using the rat cardiomyoblast (H9c2) cell model after lesinurad treatment (0.625-0.5 M) for 24 h. The half-maximal inhibitory concentration (IC50) was calculated to be 0.84 M. Necrotic cell death was induced at 0.125- 0.5 M doses and glutathione (GSH) was depleted at all studied concentrations. The ROS levels did not show significant change after lesinurad treatment, which may be a consequence of reactive oxygen species (ROS) scavenging activity of GSH. The protein expressions of troponin T and troponin I slightly decreased at the highest concentration. According to the findings, lesinurad-induced cardiotoxicity might be associated with oxidative stress and necrotic cell death. However, further detailed mechanistic studies are needed to clarify the lesinurad-induced cardiotoxic effects.

Anahtar Kelimeler

Lesinurad-1 URAT-1 inhibitors-2 gout-3 cardiotoxicity-4

Kaynakça

  • [1] Richette P, Bardin T. Gout. Lancet. 2010; 375(9711): 318-28. [CrossRef]
  • [2] Choi HK, Gout B. Epidemiology, pathology, and pathogenesis. Primer on the rheumatic diseases. 13th ed. Atlanta, GA: Arthritis Foundation, 2008; 250-256. [CrossRef]
  • [3] Maiuolo J, Oppedisano F, Gratteri S, Muscoli C, Mollace V. Regulation of uric acid metabolism and excretion. Int J Cardiol. 2016; 213: 8-14. [CrossRef]
  • [4] Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, Kaldas M et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012; 64(10): 1431-1446. [CrossRef]
  • [5] FDA. 2015. HIGHLIGHTS OF PRESCRIBING INFORMATION – ZURAMPIC https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf (accessed July 24, 2020)
  • [6] EMA 2016. ZURAMPIC. https://www.ema.europa.eu/en/documents/overview/zurampic-epar-summarypublic_en.pdf (accessed July 25 2020)
  • [7] Bardin T, Keenan RT, Khanna PP, Kopicko J, Fung M, Bhakta N, Adler S, Storgard C, Baumgartner S, So A. Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann Rheum Dis, 2017; 76(5): 811-820. [CrossRef]
  • [8] Dalbeth N, Jones G, Terkeltaub R, Khanna D, Kopicko J, Bhakta N, Adler S, Fung M, Storgard C, Baumgartner S, Perez‐Ruiz F. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with febuxostat in patients with tophaceous gout: findings of a phase III clinical trial. Arthritis Rheumatol. 2017; 69(9): 1903-1913. [CrossRef]
  • [9] Saag KG, Fitz‐Patrick D, Kopicko J, Fung M, Bhakta N, Adler S, Storgard C, Baumgartner S, Becker MA. Lesinurad combined with allopurinol: a randomized, double‐blind, placebo‐controlled study in gout patients with an inadequate response to standard‐of‐care allopurinol (a US‐based study). Arthritis Rheumatol. 2017; 69(1): 203-212. [CrossRef]
  • [10] Daubney J, Bonner PL, Hargreaves AJ, Dickenson JM. Cardioprotective and cardiotoxic effects of quercetin and two of its in vivo metabolites on differentiated H9c2 cardiomyocytes. Basic Clin Pharmacol Toxicol. 2015; 116(2): 96-109. [CrossRef]
  • [11] Gill C, Mestril R, Samali A. Losing heart: the role of apoptosis in heart disease-A novel therapeutic target? The FASEB J. 2002; 16(2): 135-146. [CrossRef]
  • [12] Perik PJ, de Vries EGE, Gietema JA, van der Graaf WTA, Sleijfer DT, Suurmeijer AJH, van Veldhuisen DJ. The dilemma of the strive for apoptosis in oncology: mind the heart. Crit Rev Oncol Hematol. 2005; 53(2): 101-113. [CrossRef]
  • [13] Foo RSY, Mani K, Kitsis RN. Death begets failure in the heart. The Journal of Clinical Investigation. 2005; 115(3): 565-571. [CrossRef]
  • [14] Olivetti G, Abbi R, Quaini F, Kajstura J, Cheng W, Nitahara JA, Quaini E, Loreto CD, Beltrami CA, Krajewski S, Reed JC. Apoptosis in the failing human heart. NEJM. 1997; 336(16): 1131-1141. [CrossRef]
  • [15] Bernuzzi F, Recalcati S, Alberghini A, Cairo G. Reactive oxygen species-independent apoptosis in doxorubicin-treated H9c2 cardiomyocytes: role for heme oxygenase-1 down-modulation. Chem Biol Interact. 2009; 177(1): 12-20. [CrossRef]
  • [16] Li S, Wang W, Niu T, Wang H, Li B, Shao L, Lai Y, Li H, Janicki JS, Wang XL, Tang D, Cui T. Nrf2 deficiency exaggerates doxorubicin-induced cardiotoxicity and cardiac dysfunction. Oxid Med Cell Longev. 2014; 2014: 748524. [CrossRef]
  • [17] Ghyasi R, Sepehri G, Mohammadi M, Badalzadeh R, Ghyasi A. Effect of mebudipine on oxidative stress and lipid peroxidation in myocardial ischemic-reperfusion injury in male rat. J Res Med Sci: The Official Journal of Isfahan University of Medical Sciences. 2012; 17(12): 1150. [CrossRef]
  • [18] Menazza S, Canton M, Sorato E, Boengler K, Schulz R, Di Lisa F. Old and new biomarkers of oxidative stress in heart failure. Drug Discov Today Ther Strateg. 2012; 9(4): e189-e198. [CrossRef]
  • [19] Costa VM, Carvalho F, Duarte JA, Bastos MDL, Remião F. The heart as a target for xenobiotic toxicity: the cardiac susceptibility to oxidative stress. Chem Res Toxicol. 2013; 26(9): 1285-1311. [CrossRef]
  • [20] Franco R, Cidlowski JA. Glutathione efflux and cell death. Antioxidants and Redox Signalling. 2012; 17(12): 1694-1713. [CrossRef]
  • [21] Sharma S, Jackson PG, Makan J. Cardiac troponins. J Clin Pathol. 2004; 57: 1025-1026. [CrossRef]
  • [22] Panteghini M, Apple FS, Christenson RH, Dati F, Mair J, Wu AH. Proposals from IFCC Committee on standardization of markers of cardiac damage (C-SMCD): recommendations on use of biochemical markers of cardiac damage in acute coronary syndromes. Scand J Clin Lab. 1999; 59(230): 103-112. [CrossRef]
  • [23] Adamcova M, Šterba M, Šimunek T, Potacova A, Popelova O, Mazurova Y, Geršl V. Troponin as a marker of myocardiac damage in drug-induced cardiotoxicity. Expert Opin Drug Saf. 2005; 4(3): 457-472. [CrossRef]
  • [24] Jankowski M, Bissonauth V, Gao L, Gangal M, Wang D, Danalache B, Wang Y, Stoyanova E, Cloutier G, Blaise G, Gutkowska J. Anti-inflammatory effect of oxytocin in rat myocardial infarction. Basic Res Cardiol. 2010; 105: 205-218. [CrossRef]
  • [25] Sehnert AJ, Huq A, Weinstein BM, Walker C, Fishman M, Stainier DY. Cardiac troponin T is essential in sarcomere assembly and cardiac contractility. Nat Genet. 2002; 31: 106-110. [CrossRef]
  • [26] Zhang Q, Li J, Peng S, Zhang Y, Qiao Y. Rosmarinic acid as a candidate in a phenotypic profiling cardio-/cytotoxicity cell model induced by doxorubicin. Molecules. 2020; 25(4): 836. [CrossRef]
  • [27] Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72(1-2): 248-254. [CrossRef]
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Toksikoloji
Bölüm Articles
Yazarlar

Merve Arici

Tugce Boran

Gül Özhan

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2022 Cilt: 26 Sayı: 6

Kaynak Göster

APA Arici, M., Boran, T., & Özhan, G. (2025). Evaluation of lesinurad-induced cardiotoxicity in cardiomyoblastic cells. Journal of Research in Pharmacy, 26(6), 1893-1899. https://doi.org/10.29228/jrp.279
AMA Arici M, Boran T, Özhan G. Evaluation of lesinurad-induced cardiotoxicity in cardiomyoblastic cells. J. Res. Pharm. Haziran 2025;26(6):1893-1899. doi:10.29228/jrp.279
Chicago Arici, Merve, Tugce Boran, ve Gül Özhan. “Evaluation of Lesinurad-Induced Cardiotoxicity in Cardiomyoblastic Cells”. Journal of Research in Pharmacy 26, sy. 6 (Haziran 2025): 1893-99. https://doi.org/10.29228/jrp.279.
EndNote Arici M, Boran T, Özhan G (01 Haziran 2025) Evaluation of lesinurad-induced cardiotoxicity in cardiomyoblastic cells. Journal of Research in Pharmacy 26 6 1893–1899.
IEEE M. Arici, T. Boran, ve G. Özhan, “Evaluation of lesinurad-induced cardiotoxicity in cardiomyoblastic cells”, J. Res. Pharm., c. 26, sy. 6, ss. 1893–1899, 2025, doi: 10.29228/jrp.279.
ISNAD Arici, Merve vd. “Evaluation of Lesinurad-Induced Cardiotoxicity in Cardiomyoblastic Cells”. Journal of Research in Pharmacy 26/6 (Haziran 2025), 1893-1899. https://doi.org/10.29228/jrp.279.
JAMA Arici M, Boran T, Özhan G. Evaluation of lesinurad-induced cardiotoxicity in cardiomyoblastic cells. J. Res. Pharm. 2025;26:1893–1899.
MLA Arici, Merve vd. “Evaluation of Lesinurad-Induced Cardiotoxicity in Cardiomyoblastic Cells”. Journal of Research in Pharmacy, c. 26, sy. 6, 2025, ss. 1893-9, doi:10.29228/jrp.279.
Vancouver Arici M, Boran T, Özhan G. Evaluation of lesinurad-induced cardiotoxicity in cardiomyoblastic cells. J. Res. Pharm. 2025;26(6):1893-9.