Protective effects of gallic acid and SGK1 inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats

Document Type : Original Article

Authors

1 Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Objective(s): Oxidative stress and serum and glucocorticoid-induced Kinase 1 gene (SGK1) perform a central role in the consequences of ischemia in the heart. This research aimed to investigate the effect of coadministration of gallic acid and the GSK650394 (as SGK1 gene inhibitor) on the ischemic complications of a rat model of cardiac ischemia/reperfusion (I/R) injury. 
Materials and Methods: Sixty male Wistar rats were divided into 6 groups with or without pretreatment with gallic acid for 10 days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A 30 min of ischemia was performed followed by a 60 min reperfusion.  In 2 groups, GSK650394 was infused 5 min before ischemia induction. Ten minutes after reperfusion commencement, cardiac marker enzyme (CK-MB, LDH, and cTn-I) activities were measured in the cardiac perfusate. At the end of reperfusion, the activity of anti-oxidant enzymes (Catalase, Superoxide dismutase, and Glutathione peroxidase), lipid peroxidation (MDA), total anti-oxidant capacity (TAC), intracellular reactive oxygen species (ROS), infarct size, and SGK1 gene expression were measured in the heart tissue. 
Results: The results indicated that dual therapy with both drugs significantly improved endogenous anti-oxidant enzyme activity and TAC more than each drug alone. However, the heart marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK1 gene expression were reduced significantly compared with the ischemic group. 
Conclusion: The results of this study suggest that concomitant administration of both drugs in the case of cardiac I/R injury may have a more beneficial effect than each one alone. 

Keywords

References

1. Broskova Z, Knezl V. Protective effect of novel pyridoindole derivatives on ischemia/reperfusion injury of the isolated rat heart. Pharmacol Rep 2011; 63: 967-974. 
2. Kumphune S, Chattipakorn S, Chattipakorn N. Role of p38 inhibition in cardiac ischemia/reperfusion injury. Eur J Clin Pharmacol 2012; 68:513-524. 
3. Simic D, Mimic-Oka J, Plješa M, Milanovic D, Radojevic S, Ivanovic B, et al. Time course of erythrocyte anti-oxidant activity in patients treated by thrombolysis for acute myocardial infarction. Jpn Heart J 2003; 44:823-832.
4. Zhao T, Wu W, Sui L, Huang Q, Nan Y, Liu J, et al. Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia-reperfusion injuries. Bioact Mater 2022; 7:47-72. 
5. Dianat M, Hamzavi GR, Badavi M, Samarbafzadeh A. Effects of losartan and vanillic acid co-administration on ischemia-reperfusion-induced oxidative stress in isolated rat heart. Iran Red Crescent Med J 2014; 16:e16664. 
6. Rashid S, Malik A, Khurshid R, Faryal U, Qazi S. The diagnostic value of biochemical cardiac markers in acute myocardial infarction.  Myocardial Infarction 2019; 23-39.
7. Naseroleslami M, Rakhshan K, Aboutaleb N, Souri F. Lavender oil attenuates myocardial ischemia/reperfusion injury through inhibition of autophagy and stimulation of angiogenesis. Iran J Sci Technol Trans Sci 2021; 45:1201-1209.
8. Lang F, Strutz-Seebohm N, Seebohm G, Lang UE. Significance of SGK1 in the regulation of neuronal function. J Physiol 2010; 588:3349-3354. 
9. Lang F, Shumilina E. Regulation of ion channels by the serum- and glucocorticoid-inducible kinase SGK1. FASEB J 2013; 27:3-12. 
10. Liu T, Yu T, Hu H, He K. Knockdown of the long non-coding RNA HOTTIP inhibits colorectal cancer cell proliferation and migration and induces apoptosis by targeting SGK1. Biomed Pharmacother 2018; 98:286-296. 
11. Conza D, Mirra P, Calì G, Tortora T, Insabato L, Fiory F, et al. The SGK1 inhibitor SI113 induces autophagy, apoptosis, and endoplasmic reticulum stress in endometrial cancer cells. J Cell Physiol 2017; 232:3735-3743. 
12. Lang F, Böhmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V. (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms. Physiol Rev 2006; 86:1151-1178. 
13. Schoenebeck B, Bader V, Zhu XR, Schmitz B, Lübbert H, Stichel CC. Sgk1, a cell survival response in neurodegenerative diseases. Mol Cell Neurosci 2005; 30:249-264. 
14. Inoue K, Leng T, Yang T, Zeng Z, Ueki T, Xiong ZG. Role of serum- and glucocorticoid-inducible kinases in stroke. J Neurochem 2016; 138:354-361. 
15. Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, et al. Gene regulation and DNA damage in the aging human brain. Nature. 2004; 429:883-891. 
16. Ramezani-Aliakbari F, Badavi M, Dianat M, Mard SA, Ahangarpour A. Effects of gallic acid on hemodynamic parameters and infarct size after ischemia-reperfusion in isolated rat hearts with alloxan-induced diabetes. Biomed Pharmacother 2017; 96:612-618. 
17. Badavi M, Sadeghi N, Dianat M, Samarbafzadeh A. Effects of gallic acid and cyclosporine on anti-oxidant capacity and cardiac markers of rat isolated heart after ischemia/reperfusion. Iran Red Crescent Med J 2014; 16:e16424. 
18. Gan W, Ren J, Li T, Lv S, Li C, Liu Z, et al. The SGK1 inhibitor EMD638683 prevents angiotensin II-induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation. Biochim Biophys Acta Mol Basis Dis. 2018; 1864:1-10. 
19. Badavi M, Sadeghi N, Dianat M, Samarbafzadeh A. Gallic acid and cyclosporine mixture and their effects on cardiac dysfunction induced by ischemia/reperfusion and eNOS/iNOS expression. Int J Cardiovasc Sci. 2017; 30:207-218. 
20. Baban B, Liu JY, Mozaffari MS. SGK-1 regulates inflammation and cell death in the ischemic-reperfused heart: pressure-related effects. Am J Hypertens 2014; 27:846-856. 
21. Javidanpour S, Dianat M, Badavi M, Mard SA. The inhibitory effect of rosmarinic acid on overexpression of NCX1 and stretch-induced arrhythmias after acute myocardial infarction in rats. Biomed Pharmacother 2018; 102:884-893.
22. Mahajan UB, Chandrayan G, Patil CR, Arya DS, Suchal K, Agrawal YO, et al. The protective effect of apigenin on myocardial injury in diabetic rats mediating activation of the PPAR-γ pathway. Int J Mol Sci 2017; 18:756. 
23. Amini N, Sakaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. Protective effects of naringin and trimetazidine on remote effect of acute renal injury on oxidative stress and myocardial injury through Nrf-2 regulation. Pharmacol Rep 2019; 71:1059-1066. 
24.Blagojevic M, Camilli G, Maxson M, Hube B, Moyes DL, Richardson JP, et al. Candidalysin triggers epithelial cellular stresses that induce necrotic death. Cell Microbiol 2021; 23:e13371.
25. Wang X, Guo Z, Ding Z, Mehta JL. Inflammation, autophagy, and apoptosis after myocardial infarction. J Am Heart Assoc 2018; 7: e008024.
26. Souri F, Rakhshan K, Erfani S, Azizi Y, Nasseri Maleki S, Aboutaleb N. Natural lavender oil (lavandula angustifolia) exerts cardioprotective effects against myocardial infarction by targeting inflammation and oxidative stress. Inflammopharmacology 2019; 27:799-807. 
27. Qin YW, Ye P, He JQ, Sheng L, Wang LY, Du J. Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a “Western-style diet” by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels. Acta Pharmacol Sin 2010; 31:1350-1358. 
28. Hamilton KL. Anti-oxidants and cardioprotection. Med Sci Sports Exerc. 2007; 39:1544-1553. 
29.Dludla PV, Nkambule BB, Jack B, Mkandla Z, Mutize T, Silvestri S, et al. Inflammation and oxidative stress in an obese state and the protective effects of gallic acid. Nutrients. 2018; 11:23. 
30. Nouri A, Salehi-Vanani N, Heidarian E. Anti-oxidant, anti-inflammatory and protective potential of gallic acid against paraquat-induced liver toxicity in male rats. Avicenna J Phytomed 2021; 11:633-644. 
31. Skrzep-Poloczek B, Poloczek J, Chelmecka E, Dulska A, Romuk E, Idzik M, et al. The oxidative stress markers in the erythrocytes and heart muscle of obese rats: relate to a high-fat diet but not to DJOS bariatric surgery. Anti-oxidants (Basel). 2020; 9:183.
32. Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal Biochem. 2017; 524:13-30. 
33. Amioka N, Miyoshi T, Otsuka H, Yamada D, Takaishi A, Ueeda M, et al. Serum malondialdehyde-modified low-density lipoprotein levels on admission predict prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention. J Cardiol 2019; 74:258-266.
34. Stanely Mainzen Prince P, Priscilla H, Devika PT. Gallic acid prevents lysosomal damage in isoproterenol induced cardiotoxicity in Wistar rats. Eur J Pharmacol 2009; 615:139-143. 
35. Shackebaei D, Hesari M, Ramezani-Aliakbari S, Hoseinkhani Z, Ramezani-Aliakbari F. Gallic acid protects against isoproterenol-induced cardiotoxicity in rats. Hum Exp Toxicol 2022; 41:1-10. 
36. Zhang Y, Murugesan P, Huang K, Cai H. NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets. Nat Rev Cardiol 2020; 17:170-194.
37. Pashkow FJ. Oxidative stress and inflammation in heart disease: do anti-oxidants have a role in treatment and/or prevention?. Int J Inflam 2011; 2011:514623.
38. Luzi F, Pannucci E, Santi L, Kenny JM, Torre L, Bernini R, et al. Gallic acid and quercetin as intelligent and active ingredients in poly (vinyl alcohol) films for food packaging. Polymers 2019; 11:1999.
39. Herring N, Paterson D. ECG diagnosis of acute ischaemia and infarction: past, present and future. QJM 2006; 99:219-230.
40. Li H, Liu Z, Wang J, Wong GT, Cheung C-W, Zhang L, et al. Susceptibility to myocardial ischemia reperfusion injury at early stage of type 1 diabetes in rats. Cardiovasc Diabetol 2013; 12:1-11.
41. Kwon SH, Pimentel DR, Remondino A, Sawyer DB, Colucci WS. H2O2 regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways. J Mol Cell Cardiol 2003; 35:615-621.
42. Lang F, Artunc F, Vallon V. The physiological impact of the serum and glucocorticoid-inducible kinase SGK1. Curr Opin Nephrol Hypertens 2009; 18:439-448.
43. Gan W, Li T, Ren J, Li C, Liu Z, Yang M. Serum-glucocorticoid-regulated kinase 1 contributes to mechanical stretch-induced inflammatory responses in cardiac fibroblasts. Mol Cell Biochem 2018; 445:67-78.
Iranian Journal of Basic Medical Sciences
Volume 26, Issue 3
March 2023
Pages 308-315

Files

Share

How to cite

Statistics