Cardioprotective effects of gallic acid in a rat ischemia-reperfusion model: role of apoptosis, inflammation, and antioxidant defense

Afshin Nazari , Faraz Souri , Vajihe Ghoranzadeh, Mehrnoosh Sedighi, Fazlollah Fathollahi Shoorabeh, Narges Khojasteh Kalansara

Abstract


Background and purpose: Heart disease is a major global health problem. Gallic acid (GA) possesses cardioprotective properties. This study aimed to evaluate the therapeutic effects of GA pretreatment in ischemia-reperfusion (I/R) and elucidate its underlying mechanisms.

Experimental approach: Forty adult male Wistar rats were subjected to this experiment. GA was given to the rats through gavage at doses of 15 and 30 mg/kg/day, 10 days before the induction of ischemia. To induce I/R, the left anterior descending coronary artery was occluded for 30 min, and reperfusion continued for 24 h. Malondialdehyde (MDA) levels, antioxidant enzyme activity, and inflammatory cytokines were assessed using kits. Myocardial injury markers were analyzed by ELISA, and infarct size was assessed through 2,3,5-triphenyltetrazolium chloride staining. Real-time polymerase chain reaction was utilized to quantify the relative gene expression of Bax and Bcl-2.

Findings/Results: The findings indicated that pretreatment with GA led to significant improvement in inflammatory cytokines, antioxidant enzyme activity, and a decrease in MDA levels. GA also decreased infarct size and myocardial injury markers significantly. Moreover, pretreatment with GA revealed a significant increase in the expression of the Bcl-2 gene, while the expression of the Bax gene decreased.

Conclusion and implications: Inclusively, the results suggested that GA may hold significant                                potential as a therapeutic agent for reducing myocardial injury in the context of I/R, with                                                         30 mg/kg/day proving more effective than 15 mg/kg/day, offering a promising path for further  investigation.

 

 


Keywords


Apoptosis; Gallic acid; Inflammation; Ischemia-reperfusion; Myocardial infarction; Oxidative stress.

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References


Buja LM. Pathobiology of myocardial ischemia and reperfusion injury: models, modes, molecular mechanisms, modulation, and clinical applications. Cardiol Rev. 2023;31(5):252-264. DOI: 10.1097/CRD.0000000000000440.

Dhalla NS, Shah AK, Adameova A, Bartekova M. Role of oxidative stress in cardiac dysfunction and subcellular defects due to ischemia-reperfusion injury. Biomedicines. 2022;10(7):1473,1-19. DOI: 10.3390/biomedicines10071473.

Algoet M, Janssens S, Himmelreich U, Gsell W, Pusovnik M, Van den Eynde J, et al. Myocardial ischemia-reperfusion injury and the influence of inflammation. Trends Cardiovasc Med. 2023;33(6):357-366. DOI: 10.1016/j.tcm.2022.02.005.

Mo Q, Zhang W, Zhu A, Backman LJ, Chen J. Regulation of osteogenic differentiation by the pro-inflammatory cytokines IL-1β and TNF-α: current conclusions and controversies. Hum Cell. 2022;35(4):957-971. DOI: 10.1007/s13577-022-00711-7.

Halade GV, Lee DH. Inflammation and resolution signaling in cardiac repair and heart failure. EBioMedicine. 2022;79:103992,1-9. DOI: 10.1016/j.ebiom.2022.103992.

Yap J, Irei J, Lozano-Gerona J, Vanapruks S, Bishop T, Boisvert WA. Macrophages in cardiac remodelling after myocardial infarction. Nat Rev Cardiol. 2023;20(6):373-385. DOI: 10.1038/s41569-022-00823-5.

Farokhian A, Rajabi A, Sheida A, Abdoli A, Rafiei M, Hadian Jazi Z, et al. Apoptosis and myocardial infarction: role of ncRNAs and exosomal ncRNAs. Epigenomics. 2023;15(5):307-334. DOI: 10.2217/epi-2022-0451.

Kim SY, Lee JP, Shin WR, Oh IH, Ahn JY, Kim YH. Cardiac biomarkers and detection methods for myocardial infarction. Mol Cell Toxicol. 2022;18(4):443-455. DOI: 10.1007/s13273-022-00287-1.

Souri F, Badavi M, Dianat M, Mard A, Sarkaki A, Razliqi RN. The protective effects of gallic acid and SGK1 inhibitor on cardiac damage and genes involved in Ca2+ homeostasis in an isolated heart model of ischemia/reperfusion injury in rat. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(7):5207-5217. DOI: 10.1007/s00210-024-02949-4.

Souri F, Badavi M, Dianat M, Mard SA, Sarkaki A. 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. Iran J Basic Med Sci. 2023;26(3):308-315. DOI: 10.22038/IJBMS.2023.68045.14874.

Dianat M, Radan M, Badavi M, Mard A, Bayati V, Goudarzi G. Evaluation the protective role of gallic acid on cardiac arrhythmias induced by oxidative stress in rat exposure to particulate matters. JSSU. 2022;30(3):4670-4681.DOI: 10.18502/ssu.v30i3.9464.

Chu C, Ru H, Chen Y, Xu J, Wang C, Jin Y. Gallic acid attenuates LPS-induced inflammation in Caco-2 cells by suppressing the activation of the NF-κB/MAPK signaling pathway. Acta Biochim Biophys Sin (Shanghai). 2024;56(6):905-915. DOI: 10.3724/abbs.2024008.

Zeng M, Su Y, Li K, Jin D, Li Q, Li Y, et al. Gallic acid inhibits bladder cancer T24 cell progression through mitochondrial dysfunction and PI3K/Akt/NF-κB signaling suppression. Front Pharmacol. 2020;11:1222,1-17. DOI: 10.3389/fphar.2020.01222.

Haghshenas M, Firouzabadi N, Akbarizadeh AR, Rashedinia M. Combination of metformin and gallic acid induces autophagy and apoptosis in human breast cancer cells. Res Pharm Sci. 2023;18(6):663-675. DOI: 10.4103/1735-5362.389956.

Rakhshan K, Azizi Y, Naderi N, Ghardashi Afousi A, Aboutaleb N. ELABELA (ELA) peptide exerts cardioprotection against myocardial infarction by targeting oxidative stress and the improvement of heart function. Int J Pept Res Ther. 2019;25:613-621.

Radmanesh E, Dianat M, Badavi M, Goudarzi G, Mard SA, Radan M. Protective effect of crocin on hemodynamic parameters, electrocardiogram parameters, and oxidative stress in isolated hearts of rats exposed to PM10. Iran J Basic Med Sci. 2022;25(4):460-467. DOI: 10.22038/IJBMS.2022.61163.13533.

Patel KJ, Panchasara AK, Barvaliya MJ, Purohit BM, Baxi SN, Vadgama VK, et al. Evaluation of cardioprotective effect of aqueous extract of Garcinia indica Linn. fruit rinds on isoprenaline-induced myocardial injury in Wistar albino rats. Res Pharm Sci. 2015;10(5):388-396. PMID: 26752987.

Aguilar Diaz De Leon J, Borges CR. Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay. J Vis Exp. 2020(159):10.3791/61122, 1-22. DOI: 10.3791/61122.

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.DOI: 10.1007/s40995-021-01123-2.

Akbar H, Mountfort S. Acute ST-segment elevation myocardial infarction (STEMI) [updated 2024 Oct 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53228.1/.PMID: 30335314.

Souri F, Badavi M, Dianat M, Mard SA, Sarkaki A. Effect of gallic acid pretreatment and SGK1 enzyme inhibition on cardiac function and inflammation in a rat model of ischemia-reperfusion injury. Rep Biochem Mol Biol. 2023;12(1):159-172. DOI: 10.52547/rbmb.12.1.159.

Sadiq IZ. Free radicals and oxidative stress: Signaling mechanisms, redox basis for human diseases, and cell cycle regulation. Curr Mol Med. 2023;23(1):13-35. DOI: 10.2174/1566524022666211222161637.

Młynarska E, Hajdys J, Czarnik W, Fularski P, Leszto K, Majchrowicz G, et al. The role of antioxidants in the therapy of cardiovascular diseases- a literature review. Nutrients. 2024;16(16):2587,1-26. DOI: 10.3390/nu16162587.

Demirci-Çekiç S, Özkan G, Avan AN, Uzunboy S, Çapanoğlu E, Apak R. Biomarkers of oxidative stress and antioxidant defense. J Pharm Biomed Anal. 2022;209:114477. DOI: 10.1016/j.jpba.2021.114477.

Hadidi M, Liñán-Atero R, Tarahi M, Christodoulou MC, Aghababaei F. The potential health benefits of gallic acid: therapeutic and food applications. Antioxidants (Basel). 2024;13(8):1001,1-59. DOI: 10.3390/antiox13081001.

Karakayali M, Ogun M, Artac I, Ilis D, Arslan A, Omar T, et al. Serum malondialdehyde levels at admission as a predictor of inhospital mortality in patients with acute coronary syndrome. Coron Artery Dis. 2025;36(3):211-217.DOI: 10.1097/MCA.0000000000001469.

Wang Y, Shou X, Wu Y, Li D. Immuno-inflammatory pathogenesis in ischemic heart disease: perception and knowledge for neutrophil recruitment. Front Immunol. 2024;15:1411301,1-10. DOI: 10.3389/fimmu.2024.1411301.

Fonseca FA, Izar MC. Role of inflammation in cardiac remodeling after acute myocardial infarction. Front Physiol. 2022;13:927163,1-6. DOI: 10.3389/fphys.2022.927163.

Matter MA, Paneni F, Libby P, Frantz S, Stähli BE, Templin C, et al. Inflammation in acute myocardial infarction: the good, the bad and the ugly. Eur Heart J. 2024;45(2):89-103. DOI: 10.1093/eurheartj/ehad486.

Patibandla S, Gupta K, Alsayouri K. Cardiac biomarkers. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. PMID: 31424800.

Czabotar PE, Garcia-Saez AJ. Mechanisms of BCL-2 family proteins in mitochondrial apoptosis. Nat Rev Mol Cell Biol. 2023;24(10):732-748. DOI: 10.1038/s41580-023-00629-4.

Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Front Oncol. 2022;12:985363,1-16. DOI: 10.3389/fonc.2022.985363.

Pepper C, Bentley P. The role of the Bcl-2 family in the modulation of apoptosis. In: Bryant J, Garland J, Hughes SG, editors. Programmed cell death in animals and plants. 1st ed. London: Garland Science; 2000.11 pages. DOI: 10.1201/9781003076889.


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