Eplerenone alleviates diabetic cardiomyopathy by modulating ER stress, oxidative stress, and NLRP3 inflammasome activation

Wu MX, Wang SH, Xie Y, Chen ZT, Guo Q, Yuan WL, et al. Interleukin-33 alleviates diabetic cardiomyopathy through regulation of Endoplasmic reticulum stress and autophagy via insulin-like growth factor-binding protein 3. J Cell Physiol. 2021;236(6):4403–19.

CAS  PubMed  Google Scholar 

Balaji R, Duraisamy R, Kumar MP. Complications of diabetes mellitus: a review. Drug Invent Today. 2019;12(1):98.

Google Scholar 

Lehrke M, Marx N. Diabetes mellitus and heart failure. Am J Cardiol. 2017;120(1S):S37–47.

CAS  PubMed  Google Scholar 

Xu J, Zhou Q, Xu W, Cai L. Endoplasmic reticulum stress and diabetic cardiomyopathy. Exp Diabetes Res. 2012;2012:827971.

PubMed  Google Scholar 

Ebrahimi SM, Bathaie SZ, Faridi N, Taghikhani M, Nakhjavani M, Faghihzadeh S. L-lysine protects C2C12 myotubes and 3T3-L1 adipocytes against high glucose damages and stresses. PLoS ONE. 2019;14(12):e0225912.

CAS  PubMed  PubMed Central  Google Scholar 

Sanjari-Pour M, Faridi N, Wang P, Bathaie SZ. Protective effect of saffron carotenoids against amyloid beta-induced neurotoxicity in differentiated PC12 cells via the unfolded protein response and autophagy. Phytother Res. 2024;38(10):4923–39.

CAS  PubMed  Google Scholar 

Lee HM, Kim JJ, Kim HJ, Shong M, Ku BJ, Jo EK. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes. 2013;62(1):194–204.

CAS  PubMed  Google Scholar 

Patel VB, Zhong JC, Grant MB, Oudit GY. Role of the ACE2/Angiotensin 1–7 Axis of the Renin-Angiotensin system in heart failure. Circ Res. 2016;118(8):1313–26.

CAS  PubMed  PubMed Central  Google Scholar 

Luther JM. Effects of aldosterone on insulin sensitivity and secretion. Steroids. 2014;91:54–60.

CAS  PubMed  Google Scholar 

Bauersachs J, Jaisser F, Toto R. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension. 2015;65(2):257–63.

CAS  PubMed  Google Scholar 

Kolkhof P, Bärfacker L. 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234(1):T125–40.

CAS  PubMed  PubMed Central  Google Scholar 

Reddy NM, Mahajan UB, Patil CR, Agrawal YO, Ojha S, Goyal SN. Eplerenone attenuates cardiac dysfunction and oxidative stress in β-receptor stimulated myocardial infarcted rats. Am J Transl Res. 2015;7(9):1602–11.

CAS  PubMed  PubMed Central  Google Scholar 

Egan BM, Li J. Role of aldosterone Blockade in resistant hypertension. Semin Nephrol. 2014;34(3):273–84.

CAS  PubMed  Google Scholar 

Schafer A, Vogt C, Fraccarollo D, Widder J, Flierl U, Hildemann SK, et al. Eplerenone improves vascular function and reduces platelet activation in diabetic rats. J Physiol Pharmacol. 2010;61(1):45–52.

CAS  PubMed  Google Scholar 

Yousefian M, Abedimanesh S, Yadegar A, Nakhjavani M, Bathaie SZ. Co-administration of L-Lysine, vitamin C, and zinc increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats. Biomed Pharmacother. 2024;174:116525.

CAS  PubMed  Google Scholar 

Samarghandian S, Rajabi S, Aschner M, Noferesti V, Farkhondeh T. Oxidative stress and apoptotic index modifications in the hippocampus of rat pups born to mothers exposed to buprenorphine during lactation. Toxicol Rep. 2022;9:2050–4.

CAS  PubMed  PubMed Central  Google Scholar 

Ramírez E, Klett-Mingo M, Ares-Carrasco S, Picatoste B, Ferrarini A, Rupérez FJ, et al. Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes. Cardiovasc Diabetol. 2013;12:172.

PubMed  PubMed Central  Google Scholar 

Aragno M, Mastrocola R, Alloatti G, Vercellinatto I, Bardini P, Geuna S, et al. Oxidative stress triggers cardiac fibrosis in the heart of diabetic rats. Endocrinology. 2008;149(1):380–8.

CAS  PubMed  Google Scholar 

Zaky AS, Kandeil M, Abdel-Gabbar M, Fahmy EM, Almehmadi MM, Ali TM, et al. The antidiabetic effects and modes of action of the Balanites aegyptiaca fruit and seed aqueous extracts in NA/STZ-Induced diabetic rats. Pharmaceutics. 2022;14(2):263.

CAS  PubMed  PubMed Central  Google Scholar 

Balogh DB, Molnar A, Degi A, Toth A, Lenart L, Saeed A, et al. Cardioprotective and antifibrotic effects of Low-Dose Renin-Angiotensin-Aldosterone system inhibitors in type 1 diabetic rat model. Int J Mol Sci. 2023;24(23):17043.

CAS  PubMed  PubMed Central  Google Scholar 

Mahajan UB, Chandrayan G, Patil CR, Arya DS, Suchal K, Agrawal Y, et al. Eplerenone attenuates myocardial infarction in diabetic rats via modulation of the PI3K-Akt pathway and phosphorylation of GSK-3β. Am J Transl Res. 2018;10(9):2810–21.

CAS  PubMed  PubMed Central  Google Scholar 

Tsai CH, Pan CT, Chang YY, Peng SY, Lee PC, Liao CW, et al. Aldosterone excess induced mitochondria decrease and dysfunction via mineralocorticoid receptor and oxidative stress in vitro and in vivo. Biomedicines. 2021;9(8):946.

CAS  PubMed  PubMed Central  Google Scholar 

Manrique C, Lastra G, Gardner M, Sowers JR. The Renin angiotensin aldosterone system in hypertension: roles of insulin resistance and oxidative stress. Med Clin North Am. 2009;93(3):569–82.

CAS  PubMed  PubMed Central  Google Scholar 

Lakshmanan AP, Harima M, Suzuki K, Soetikno V, Nagata M, Nakamura T, et al. The hyperglycemia stimulated myocardial Endoplasmic reticulum (ER) stress contributes to diabetic cardiomyopathy in the Transgenic non-obese type 2 diabetic rats: a differential role of unfolded protein response (UPR) signaling proteins. Int J Biochem Cell Biol. 2013;45(2):438–47.

CAS  PubMed  Google Scholar 

Piao M, Liu Y, Yu T, Liu D, Wang X, Song Y, et al. Dietary zinc reduces Endoplasmic reticulum stress and autophagy to protect against diabetic renal damage in streptozotocin-induced diabetic rats. Int J Diabetes Dev Ctries. 2019;39:340–5.

CAS  Google Scholar 

Yuan Y, Xu X, Zhao C, Zhao M, Wang H, Zhang B, et al. The roles of oxidative stress, Endoplasmic reticulum stress, and autophagy in aldosterone/mineralocorticoid receptor-induced podocyte injury. Lab Invest. 2015;95(12):1374–86.

CAS  PubMed  Google Scholar 

Senft D, Ronai ZA. UPR, autophagy, and mitochondria crosstalk underlies the ER stress response. Trends Biochem Sci. 2015;40(3):141–8.

CAS  PubMed  PubMed Central  Google Scholar 

Wang XZ, Lawson B, Brewer JW, Zinszner H, Sanjay A, Mi LJ, et al. Signals from the stressed Endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol Cell Biol. 1996;16(8):4273–80.

CAS  PubMed  PubMed Central  Google Scholar 

Li W, Cao T, Luo C, Cai J, Zhou X, Xiao X, et al. Crosstalk between ER stress, NLRP3 inflammasome, and inflammation. Appl Microbiol Biotechnol. 2020;104(14):6129–40.

CAS  PubMed  Google Scholar 

Kadoya H, Satoh M, Sasaki T, Taniguchi S, Takahashi M, Kashihara N. Excess aldosterone is a critical danger signal for inflammasome activation in the development of renal fibrosis in mice. FASEB J. 2015;29(9):3899–910.

CAS  PubMed  Google Scholar 

Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic Islets. J Clin Invest. 2002;110(6):851–60.

CAS  PubMed  PubMed Central  Google Scholar 

Wada T, Ishikawa A, Watanabe E, Nakamura Y, Aruga Y, Hasegawa H, et al. Eplerenone prevented obesity-induced inflammasome activation and glucose intolerance. J Endocrinol. 2017;235(3):179–91.

CAS  PubMed  Google Scholar 

Xie L, Zang D, Yang J, Xue F, Sui W, Zhang Y. Combination of ADAM17 knockdown with eplerenone is more effective than single therapy in ameliorating diabetic cardiomyopathy. Front Pharmacol. 2024;15:1364827.

CAS  PubMed  PubMed Central  Google Scholar 

Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.

CAS  PubMed  Google Scholar 

Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309–21.

CAS  PubMed 

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