Iranian Heart Journal

Iranian Heart Journal

Evaluation of the Effects of p-Coumaric Acid on Oxidative Stress, Electrocardiographic Parameters, and Cardiac Arrhythmias in a CaCl2-Induced Arrhythmia Model in Rats

Document Type : Original Article

Authors
Mohammadreza Naderi 1
Mahin Dianat 2
Mohammad Badavi 2
Zahra Mansouri 2
1 Department of Physiology, Faculty of Medicine, Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 Department of Physiology, Faculty of Medicine, Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.
Abstract
Background: Cardiovascular diseases remain a leading global cause of mortality, with sudden cardiac death-primarily resulting from arrhythmias-accounting for nearly half of these fatalities. Limited research has explored the impact of p-coumaric acid (P-co) on chemically induced arrhythmias. Given the cardioprotective role of antioxidants, this study aimed to investigate the effects of P-co on oxidative stress, electrocardiographic (ECG) parameters, and cardiac arrhythmias in Wistar rats using a calcium chloride (CaCl2)-induced arrhythmia model.
 
Methods: Forty-eight Wistar rats were divided into 6 groups: (1) Control (normal saline); (2) CaCl2 (normal saline + CaCl2 140 mg/kg); (3–5) CaCl2 + P-co 25, 50, and 100 mg/kg, respectively; and (6) P-co 100 mg/kg. P-co was administered orally for 10 consecutive days, followed by an intravenous injection of CaCl2 via the femoral vein on the final day. Electrophysiological assessment and arrhythmia evaluation were conducted using lead II ECG. Furthermore, biochemical analyses measured oxidative stress and cardiac injury markers, including MDA, CK-MB, LDH, SOD, CAT, and GPx, across all groups.
 
Results: Intravenous injection of CaCl2 led to significant changes in ECG parameters and the development of arrhythmias. Pretreatment with P-co significantly improved the observed changes. Compared with the CaCl2 group, P-co pretreatment reduced cardiac damage markers and lipid peroxidation and enhanced antioxidant enzymes.
 
Conclusions: The results of this study suggest that the intravenous administration of CaCl2 induces cardiac arrhythmias and oxidative stress in heart tissue. As a natural polyphenol and antioxidant, P-co exhibited a protective effect against CaCl2-induced cardiac damage. (Iranian Heart Journal 2026; 27(2): 65-80)
Keywords
CaCl2
p-coumaric acid
arrhythmia
oxidative stress
1.         Hung MY, Kounis NG, Lu MY, Hu P. Myocardial Ischemic Syndromes, Heart Failure Syndromes, Electrocardiographic Abnormalities, Arrhythmic Syndromes and Angiographic Diagnosis of Coronary Artery Spasm: Literature Review. Int J Med Sci. 2020; 17(8):1071-82.
2.         Xu M, Yang X. Double hazards of ischemia and reperfusion arrhythmias in a patient with variant angina pectoris. J Electrocardiol. 2015;48(4):739-43.
3.         Yesin M, Kalcik M, Gursoy MO, Karakoyun S, Cagdas M, Ozkan M. Acute myocardial infarction in a patient suffering from penicillin-induced laryngeal edema : Kounis syndrome aggravated by adrenaline. Wien Klin Wochenschr. 2017; 129(13-14):509-11.
4.         Chiwhane A, Pradeep. Study of Rhythm Disturbances in Acute Myocardial Infarction. J Assoc Physicians India. 2018; 66(1):54-8.
5.         Riad O, Russell C, Garfield B, Behar JM. Atrial pacing to suppress ventricular arrhythmias in the critically ill patients: a case report. Eur Heart J Case Rep. 2022; 6(5):ytac163.
6.         Salinas P, Lopez-de-Sa E, Pena-Conde L, Viana-Tejedor A, Rey-Blas JR, Armada E, et al. Electrocardiographic changes during induced therapeutic hypothermia in comatose survivors after cardiac arrest. World J Cardiol. 2015; 7(7):423-30.
7.         Bhandari A, Woodruff R, 3rd, Murthy A. A large hiatal hernia causing frequent premature ventricular contractions with bigeminy: A case report and review of literature. J Cardiol Cases. 2023; 28(1):36-9.
8.         Hu D, Li J. Rapid wide QRS tachycardia with an unknown cause. Ann Noninvasive Electrocardiol. 2022; 27(5):e12959.
9.         Erath JW, Hohnloser SH. Drugs to prevent sudden cardiac death. Int J Cardiol. 2017; 237:22-4.
10.      Kasper S. Choosing among second-generation antidepressant treatments for depressed patients with cardiac diseases. Int J Psychiatry Clin Pract. 2019; 23(2):134-48.
11.      Jakubczyk K, Dec K, Kaldunska J, Kawczuga D, Kochman J, Janda K. Reactive oxygen species - sources, functions, oxidative damage. Pol Merkur Lekarski. 2020; 48(284):124-7.
12.      Khramtsov VV. In Vivo Electron Paramagnetic Resonance: Radical Concepts for Translation to the Clinical Setting. Antioxid Redox Signal. 2018;28(15):1341-4.
13.      Kotoda M, Ino H, Kumakura Y, Iijima T, Ishiyama T, Matsukawa T. Analgesic effects of amiodarone in mouse models of pain. J Pain Res. 2019; 12:1825-32.
14.      Williams EA, Russo V, Ceraso S, Gupta D, Barrett-Jolley R. Anti-arrhythmic properties of non-antiarrhythmic medications. Pharmacol Res. 2020; 156:104762.
15.      Ermakov S, Scheinman M. Arrhythmogenic Right Ventricular Cardiomyopathy - Antiarrhythmic Therapy. Arrhythm Electrophysiol Rev. 2015; 4(2):86-9.
16.      Mujovic N, Dobrev D, Marinkovic M, Russo V, Potpara TS. The role of amiodarone in contemporary management of complex cardiac arrhythmias. Pharmacol Res. 2020; 151:104521.
17.      Cao Z-P, Zhang Y, Mi L, Luo X-Y, Tian M-H, Zhu B-L. The expression of B-type natriuretic peptide after CaCl2-induced arrhythmias in rats. The American Journal of Forensic Medicine and Pathology. 2016; 37(3):133-40.
18.      Abdelsalam SA, Renu K, Zahra HA, Abdallah BM, Ali EM, Veeraraghavan VP, et al. Polyphenols Mediate Neuroprotection in Cerebral Ischemic Stroke-An Update. Nutrients. 2023; 15(5).
19.      Miranda AR, Albrecht C, Cortez MV, Soria EA. Pharmacology and Toxicology of Polyphenols with Potential As Neurotropic Agents in Non-communicable Diseases. Curr Drug Targets. 2018; 19(2):97-110.
20.      Kazemzadeh R, Khorsandi L, Radan M, Ghafouri S, Mard SA. Pretreatment with p-coumaric acid protect rat’s liver against ischemia-reperfusion injury. Physiology and Pharmacology. 2021; 25(1):69-75.
21.      Malik N, Dhiman P. New Approaches and Advancements in Drug Development from Phenolic P-coumaric Acid. Curr Top Med Chem. 2022; 22(18):1515-29.
22.      Pei K, Ou J, Huang J, Ou S. p-Coumaric acid and its conjugates: dietary sources, pharmacokinetic properties and biological activities. J Sci Food Agric. 2016; 96(9):2952-62.
23.      Dianat M, Akbari G. Protective effect of hydroalcoholic extract of hawthorn fruit on CaCl2-induced arrhythmias in rat. Jundishapur Scientific Medical Journal. 2014; 12(6):693-703.
24.      Kheiry M, Dianat M, Badavi M, Mard SA, Bayati V. p-Coumaric acid protects cardiac function against lipopolysaccharide-induced acute lung injury by attenuation of oxidative stress. Iranian Journal of Basic Medical Sciences. 2019; 22(8):949.
25.      Dianat M, Amini N, Badavi M, Farbood Y. Ellagic acid improved arrhythmias induced by CaCL2 in the rat stress model. Avicenna Journal of Phytomedicine. 2015; 5(2):120.
26.      Cheng D, Xi Y, Cao J, Cao D, Ma Y, Jiang W. Protective effect of apple (Ralls) polyphenol extract against aluminum-induced cognitive impairment and oxidative damage in rat. Neurotoxicology. 2014; 45:111-20.
27.      Dianat M, Radan M, Badavi M, Mard SA, Bayati V, Ahmadizadeh M. Crocin attenuates cigarette smoke-induced lung injury and cardiac dysfunction by anti-oxidative effects: the role of Nrf2 antioxidant system in preventing oxidative stress. Respiratory research. 2018; 19:1-20.
28.      Gaur U, Gadkari C, Pundkar A, Gaur Jr U. Associated factors and mortality of arrhythmia in emergency department: A narrative review. Cureus. 2024; 16(9).
29.      Klabunde RE. Cardiac electrophysiology: normal and ischemic ionic currents and the ECG. Adv Physiol Educ. 2017;41(1):29-37.
30.      Kramer J, Nordbeck P, Stork S, Ritter C, Ertl G, Wanner C, et al. Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy. JIMD Rep. 2015;28:19-28.
31.      Vazquez-Gonzalez KI, Ochoa-Brust A, Rodriguez-Hernandez A, Ventura-Cisneros H, Lino-Lopez GJ, Barbosa-Valdovinos R, et al. Cardiac alterations induced by Heloderma horridum horridum venom in rats: An experimental study with ECG analysis using a linear regression algorithm. Toxicon. 2024; 249:108062.
32.      Kingma J, Simard C, Drolet B. Overview of Cardiac Arrhythmias and Treatment Strategies. Pharmaceuticals (Basel). 2023; 16(6).
33.      Chen SM, Sun C, Wang XY, Zhang Y, Liu SW. [Arrhythmogenic right ventricular cardiomyopathy associated with arrhythmia-induced cardiomyopathy: A case report]. Beijing Da Xue Xue Bao Yi Xue Ban. 2021; 53(5):1002-6.
34.      Pelter MM, Suba S, Sandoval C, Zegre-Hemsey JK, Berger S, Larsen A, et al. Actionable Ventricular Tachycardia During In-Hospital ECG Monitoring and Its Impact on Alarm Fatigue. Crit Pathw Cardiol. 2020; 19(2):79-86.
35.      Campos FO, Shiferaw Y, Vigmond EJ, Plank G. Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias. Chaos. 2017; 27(9):093910.
36.      Cluitmans MJM, Bear LR, Nguyen UC, van Rees B, Stoks J, Ter Bekke RMA, et al. Noninvasive detection of spatiotemporal activation-repolarization interactions that prime idiopathic ventricular fibrillation. Sci Transl Med. 2021; 13(620):eabi9317.
37.      Yozgat CY, Yesilbas O, Iscan A, Yurtsever I, Temur HO, Bayramova N, et al. Development of Antiarrhythmic Therapy-Resistant Ventricular Tachycardia, Ventricular Fibrillation, and Premature Ventricular Contractions in a 15-Year-Old Patient. J Pediatr Intensive Care. 2022; 11(1):72-6.
38.      Khaksar MA, Purchini P, Radan M, Dianat M. Protective effects of the combination of exercise and gallic acid supplementation on cardiac system in CaCl2-induced arrhythmias model in rats. Jundishapur Journal of Physiology. 2018; 1(1):12-6.
39.      Kheradmandpour M, Aminifar SA, Dianat M. The effect of hydro-alcoholic extract of Ocimum basilicum on CaCl2-induced cardiac arrhythmias in rats. Jentashapir Journal of Cellular and Molecular Biology. 2020; 11(4).
40.      Amini N, Sarkaki 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. Pharmacological Reports. 2019; 71(6):1059-66.
41.      Liu Y, Qu X, Zhang J, Wang X, Wang J. Effects of dexmedetomidine on the degree of myocardial ischemia-reperfusion injury, oxidative stress and TLR4/NF-κB signaling pathway in rats. Pakistan Journal of Pharmaceutical Sciences. 2021; 34.
42.      Ponnian SMP, Stanely SP, Roy AJ. Cardioprotective effects of p-coumaric acid on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance in isoproterenol-induced experimental myocardial infarction. J Biochem Mol Toxicol. 2024; 38(3):e23668.
43.      Douiri S, Bahdoudi S, Hamdi Y, Cubi R, Basille M, Fournier A, et al. Involvement of endogenous antioxidant systems in the protective activity of pituitary adenylate cyclase-activating polypeptide against hydrogen peroxide-induced oxidative damages in cultured rat astrocytes. J Neurochem. 2016; 137(6):913-30.
44.      Liu D, Yue Y, Ping L, Sun C, Zheng T, Cheng Y, et al. Lactobacillus delbrueckii subsp. bulgaricus 1.0207 Exopolysaccharides Attenuate Hydrogen Peroxide-Induced Oxidative Stress Damage in IPEC-J2 Cells through the Keap1/Nrf2 Pathway. Antioxidants (Basel). 2024; 13(9).
45.      Shen Y, Song X, Li L, Sun J, Jaiswal Y, Huang J, et al. Protective effects of p-coumaric acid against oxidant and hyperlipidemia-an in vitro and in vivo evaluation. Biomed Pharmacother. 2019; 111:579-87.
Iranian Heart Journal
Volume 27, Issue 2
Spring 2026
Pages 65-80