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Published in: Cardiovascular Toxicology 4/2016

01-10-2016

Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat

Authors: Kais Mnafgui, Raouf Hajji, Fatma Derbali, Anis Gammoudi, Gaddour Khabbabi, Hedi Ellefi, Noureddine Allouche, Adel Kadri, Neji Gharsallah

Published in: Cardiovascular Toxicology | Issue 4/2016

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Abstract

This study aimed to evaluate the antithrombotic, anti-inflammatory and anti-cardiac remodeling properties of eugenol in isoproterenol-induced myocardial infarction in rats. Male Wistar rats were randomly divided into four groups, control, iso [100 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI] and pretreated animals with clopidogrel (0.2 mg/kg) and eugenol (50 mg/kg) orally for 7 days and intoxicated with isoproterenol (Iso + Clop) and (Iso + EG) groups. Isoproterenol-induced myocardial infarcted rats showed notable changes in the ECG pattern, increase in heart weight index, deterioration in the hemodynamic function and rise in plasma level of troponin-T, CK-MB and LDH and ALT by 316, 74, 172 and 45 %, respectively, with histological myocardium necrosis and cells inflammatory infiltration. In addition, significant increases in plasma levels of inflammatory biomarkers such as fibrinogen, α1, α2, β1, β2 and γ globulins with decrease level of albumin were observed in infarcted rats as compared to normal ones. Else, the angiotensin-converting enzyme (ACE) activity in plasma, kidney and heart of the isoproterenol-induced rats was significantly increased by 34, 47 and 93 %, respectively, as compared to normal group. However, the administration of eugenol induced a clear improvement in cardiac biomarkers injury, reduced inflammatory mediators proteins, increased heart activities of superoxide dismutase and glutathione peroxidase with reduce in thiobarbituric acid-reactive substances content and inhibition of ventricular remodeling process through inhibition of ACE activity. Overall, eugenol evidences high preventive effects from cardiac remodeling process.
Literature
1.
go back to reference White, M. Y., Edwards, A. G., Cordwell, S. J., & Van Eyk, J. E. (2008). Mitochondria: A mirror into cellular dysfunction in heart disease. Proteomics-Clinical Applications, 2, 845–861.CrossRefPubMed White, M. Y., Edwards, A. G., Cordwell, S. J., & Van Eyk, J. E. (2008). Mitochondria: A mirror into cellular dysfunction in heart disease. Proteomics-Clinical Applications, 2, 845–861.CrossRefPubMed
2.
go back to reference Ross, R. (1999). Atherosclerosis-an inflammatory disease. New England Journal of Medicine, 340, 115–126.CrossRefPubMed Ross, R. (1999). Atherosclerosis-an inflammatory disease. New England Journal of Medicine, 340, 115–126.CrossRefPubMed
3.
go back to reference Hong, M. K., Mintz, G. S., Lee, C. W., Kim, Y. H., Lee, S. W., Song, J. M., et al. (2004). Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: A three-vessel intravascular ultrasound study in 235 patients. Circulation, 110, 928–933.CrossRefPubMed Hong, M. K., Mintz, G. S., Lee, C. W., Kim, Y. H., Lee, S. W., Song, J. M., et al. (2004). Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: A three-vessel intravascular ultrasound study in 235 patients. Circulation, 110, 928–933.CrossRefPubMed
4.
go back to reference Lopez, A. D., Mathers, C. D., Ezzati, M., Jamison, D. T., & Murray, C. J. (2006). Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet, 367, 1747–1757.CrossRefPubMed Lopez, A. D., Mathers, C. D., Ezzati, M., Jamison, D. T., & Murray, C. J. (2006). Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet, 367, 1747–1757.CrossRefPubMed
5.
go back to reference Cohn, J. N., Ferrari, R., & Sharpe, N. (2000). Cardiac remodeling—concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. Journal of the American College of Cardiology, 35, 569–582.CrossRefPubMed Cohn, J. N., Ferrari, R., & Sharpe, N. (2000). Cardiac remodeling—concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. Journal of the American College of Cardiology, 35, 569–582.CrossRefPubMed
6.
go back to reference Salloum, F. N., Abbate, A., Das, A., Houser, J. E., Mudrick, C. A., Qureshi, I. Z., et al. (2008). Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice. American Journal of Physiology: Heart and Circulation Physiology, 294, 398–406. Salloum, F. N., Abbate, A., Das, A., Houser, J. E., Mudrick, C. A., Qureshi, I. Z., et al. (2008). Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice. American Journal of Physiology: Heart and Circulation Physiology, 294, 398–406.
7.
go back to reference Mnafgui, K., Hajji, R., Derbali, F., Khlif, I., Kraiem, F., Ellefi, H., et al. (2015). Protective effect of hydroxytyrosol against cardiac remodeling after isoproterenol-induced myocardial infarction in rat. Cardiovascular Toxicology. doi:10.1007/s12012-015-9323-1.PubMed Mnafgui, K., Hajji, R., Derbali, F., Khlif, I., Kraiem, F., Ellefi, H., et al. (2015). Protective effect of hydroxytyrosol against cardiac remodeling after isoproterenol-induced myocardial infarction in rat. Cardiovascular Toxicology. doi:10.​1007/​s12012-015-9323-1.PubMed
8.
go back to reference Borghi, C., Bacchelli, S., Esposti, D. D., & Ambrosioni, E. (2006). Effects of early angiotensin-converting enzyme inhibition in patients with non–ST-elevation acute anterior myocardial infarction. American Heart Journal, 152, 470–477.CrossRefPubMed Borghi, C., Bacchelli, S., Esposti, D. D., & Ambrosioni, E. (2006). Effects of early angiotensin-converting enzyme inhibition in patients with non–ST-elevation acute anterior myocardial infarction. American Heart Journal, 152, 470–477.CrossRefPubMed
9.
go back to reference Mnafgui, K., Khlif, I., Hajji, R., Derbali, F., Kraiem, F., Ellefi, H., et al. (2015). Preventive effects of oleuropein against cardiac remodeling after myocardial infarction in Wistar rat through inhibiting angiotensin-converting enzyme activity. Journal of Toxicology Mechanisms and Methods. doi:10.3109/15376516.2015.1053648.PubMed Mnafgui, K., Khlif, I., Hajji, R., Derbali, F., Kraiem, F., Ellefi, H., et al. (2015). Preventive effects of oleuropein against cardiac remodeling after myocardial infarction in Wistar rat through inhibiting angiotensin-converting enzyme activity. Journal of Toxicology Mechanisms and Methods. doi:10.​3109/​15376516.​2015.​1053648.PubMed
10.
go back to reference Srinivasan, S., Sathish, G., Jayanthi, M., Muthukumaran, J., Muruganathan, U., & Ramachandran, V. (2014). Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin induced diabetic rats. Journal of Molecular and Cellular Biochemistry, 385, 159–168.CrossRefPubMed Srinivasan, S., Sathish, G., Jayanthi, M., Muthukumaran, J., Muruganathan, U., & Ramachandran, V. (2014). Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin induced diabetic rats. Journal of Molecular and Cellular Biochemistry, 385, 159–168.CrossRefPubMed
11.
go back to reference Mnafgui, K., Kaanich, F., Derbali, A., Hamden, K., Derbali, F., Slama, S., et al. (2013). Inhibition of key enzymes related to diabetes and hypertension by eugenol in vitro and in alloxan-induced diabetic rats. Archive of Physiology and Biochemistry, 119, 225–233.CrossRef Mnafgui, K., Kaanich, F., Derbali, A., Hamden, K., Derbali, F., Slama, S., et al. (2013). Inhibition of key enzymes related to diabetes and hypertension by eugenol in vitro and in alloxan-induced diabetic rats. Archive of Physiology and Biochemistry, 119, 225–233.CrossRef
12.
go back to reference Fraga, C. G., Leibovitz, B. E., & Toppel, A. L. (1988). Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: Characterization and comparison with homogenates and microsomes. Free Radical Biology and Medicine, 4, 155–161.CrossRefPubMed Fraga, C. G., Leibovitz, B. E., & Toppel, A. L. (1988). Lipid peroxidation measured as thiobarbituric acid-reactive substances in tissue slices: Characterization and comparison with homogenates and microsomes. Free Radical Biology and Medicine, 4, 155–161.CrossRefPubMed
13.
go back to reference Kakkar, P., Das, B., & Viswanathan, P. N. (1984). A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry & Biophysics, 21, 130–132. Kakkar, P., Das, B., & Viswanathan, P. N. (1984). A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry & Biophysics, 21, 130–132.
14.
go back to reference Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., & Hoekstra, W. G. (1973). Selenium: Biochemical role as a component of glutathione peroxidase. Science, 179, 588–590.CrossRefPubMed Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., & Hoekstra, W. G. (1973). Selenium: Biochemical role as a component of glutathione peroxidase. Science, 179, 588–590.CrossRefPubMed
15.
go back to reference Kannan, M. M., & Quine, S. D. (2011). Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study. European Journal of Pharmacology, 659, 45–52.CrossRefPubMed Kannan, M. M., & Quine, S. D. (2011). Ellagic acid ameliorates isoproterenol induced oxidative stress: Evidence from electrocardiological, biochemical and histological study. European Journal of Pharmacology, 659, 45–52.CrossRefPubMed
16.
go back to reference Whalen, E. J., & Lewis, S. J. (1999). In vivo evidence that isoproterenol may increase heart rate in the rat by mechanisms in addition to activation of cardiac b1-or b2-adrenoceptors. European Journal of Pharmacology, 382, 207–210.CrossRefPubMed Whalen, E. J., & Lewis, S. J. (1999). In vivo evidence that isoproterenol may increase heart rate in the rat by mechanisms in addition to activation of cardiac b1-or b2-adrenoceptors. European Journal of Pharmacology, 382, 207–210.CrossRefPubMed
17.
go back to reference Upaganlawar, A., Gandhi, H., & Balaraman, R. (2011). Isoproterenol induced myocardial infarction: Protective role of natural products. Journal of Pharmacology and Toxicology, 6, 1–17. Upaganlawar, A., Gandhi, H., & Balaraman, R. (2011). Isoproterenol induced myocardial infarction: Protective role of natural products. Journal of Pharmacology and Toxicology, 6, 1–17.
18.
go back to reference Damiania, E. N., Rossonia, L. V., & Vassalloa, D. V. (2003). Vasorelaxant effects of eugenol on rat thoracic aorta. Vascular Pharmacology, 40, 59–66.CrossRef Damiania, E. N., Rossonia, L. V., & Vassalloa, D. V. (2003). Vasorelaxant effects of eugenol on rat thoracic aorta. Vascular Pharmacology, 40, 59–66.CrossRef
19.
go back to reference Choudhary, R., Mishra, K. P., & Subramanyam, C. (2006). Prevention of isoproterenol-induced cardiac hypertrophy by eugenol, an antioxidant. Indian Journal of Clinical Biochemistry, 21, 107–113.CrossRefPubMedPubMedCentral Choudhary, R., Mishra, K. P., & Subramanyam, C. (2006). Prevention of isoproterenol-induced cardiac hypertrophy by eugenol, an antioxidant. Indian Journal of Clinical Biochemistry, 21, 107–113.CrossRefPubMedPubMedCentral
20.
go back to reference Lahlou, S., Interaminense, L. F. L., Magalhães, P. J. C., Leal-Cardoso, J. H., & Duarte, G. P. (2004). Cardiovascular effects of eugenol, a phenolic compound present in many plant essential oils, in normotensive rats. Journal of Cardiovascular Pharmacology, 43, 250–257.CrossRefPubMed Lahlou, S., Interaminense, L. F. L., Magalhães, P. J. C., Leal-Cardoso, J. H., & Duarte, G. P. (2004). Cardiovascular effects of eugenol, a phenolic compound present in many plant essential oils, in normotensive rats. Journal of Cardiovascular Pharmacology, 43, 250–257.CrossRefPubMed
21.
go back to reference Gasparyan, A. Y. (2012). Cardiovascular risk and inflammation: Pathophysiological mechanisms, drug design, and targets. Current Pharmaceutical Design, 18, 1447–1449.CrossRefPubMed Gasparyan, A. Y. (2012). Cardiovascular risk and inflammation: Pathophysiological mechanisms, drug design, and targets. Current Pharmaceutical Design, 18, 1447–1449.CrossRefPubMed
22.
go back to reference Lindahl, B., Toss, H., Siegbahn, A., Venge, P., & Wallentin, L. (2000). Markers of myocardial damage and inflammation in relation to long term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during instability in Coronary Artery Disease. New England Journal of Medicine, 343, 1139–1147.CrossRefPubMed Lindahl, B., Toss, H., Siegbahn, A., Venge, P., & Wallentin, L. (2000). Markers of myocardial damage and inflammation in relation to long term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during instability in Coronary Artery Disease. New England Journal of Medicine, 343, 1139–1147.CrossRefPubMed
23.
go back to reference Biasucci, L. M., Liuzzo, G., Grillo, R. L., Caligiuri, G., Rebuzzi, A. G., Buffon, A., et al. (1999). Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation, 99, 855–860.CrossRefPubMed Biasucci, L. M., Liuzzo, G., Grillo, R. L., Caligiuri, G., Rebuzzi, A. G., Buffon, A., et al. (1999). Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation, 99, 855–860.CrossRefPubMed
24.
go back to reference Maresca, G., Di Blasio, A., Marchioli, R., & Di Minno, G. (1999). Measuring plasma fibrinogen to predict stroke and myocardial infarction: An update. Arteriosclerosis, Thrombosis, and Vascular Biology, 19, 1368–1377.CrossRefPubMed Maresca, G., Di Blasio, A., Marchioli, R., & Di Minno, G. (1999). Measuring plasma fibrinogen to predict stroke and myocardial infarction: An update. Arteriosclerosis, Thrombosis, and Vascular Biology, 19, 1368–1377.CrossRefPubMed
25.
go back to reference De Sutter, J., De Buyzere, M., Gheeraert, P., Van de Wiele, C., Voet, J., De Pauw, M., et al. (2001). Fibrinogen and C-reactive protein on admission as markers of final infarct size after primary angioplasty for acute myocardial infarction. Atherosclerosis, 157, 189–196.CrossRefPubMed De Sutter, J., De Buyzere, M., Gheeraert, P., Van de Wiele, C., Voet, J., De Pauw, M., et al. (2001). Fibrinogen and C-reactive protein on admission as markers of final infarct size after primary angioplasty for acute myocardial infarction. Atherosclerosis, 157, 189–196.CrossRefPubMed
26.
go back to reference Lubrano, V., & Balzan, S. (2015). Consolidated and emerging inflammatory markers in coronary artery disease. World Journal of Experimental Medicine, 5, 21–32.CrossRefPubMedPubMedCentral Lubrano, V., & Balzan, S. (2015). Consolidated and emerging inflammatory markers in coronary artery disease. World Journal of Experimental Medicine, 5, 21–32.CrossRefPubMedPubMedCentral
27.
go back to reference Badimon, L., Chesebro, J. H., & Badimon, J. J. (1992). Thrombus formation on ruptured atherosclerotic plaques and rethrombosis on evolving thrombi. Circulation, 86, 74–85. Badimon, L., Chesebro, J. H., & Badimon, J. J. (1992). Thrombus formation on ruptured atherosclerotic plaques and rethrombosis on evolving thrombi. Circulation, 86, 74–85.
28.
go back to reference Reinhart, W. H. (2003). Fibrinogen -marker or mediator of vascular disease? Vascular Medicine, 8, 211–216.CrossRefPubMed Reinhart, W. H. (2003). Fibrinogen -marker or mediator of vascular disease? Vascular Medicine, 8, 211–216.CrossRefPubMed
29.
go back to reference Coppola, G., Rizzo, M., Abrignani, M. G., Corrado, E., Di Girolamo, A., Braschi, A., et al. (2005). Fibrinogen as a predictor of mortality after acute myocardial infarction: A forty-two-month follow-up study. Italian Heart Journal, 6, 315–322.PubMed Coppola, G., Rizzo, M., Abrignani, M. G., Corrado, E., Di Girolamo, A., Braschi, A., et al. (2005). Fibrinogen as a predictor of mortality after acute myocardial infarction: A forty-two-month follow-up study. Italian Heart Journal, 6, 315–322.PubMed
30.
go back to reference Kannan, M. M., & Quine, D. S. (2013). Ellagic acid inhibits cardiac arrhythmias, hypertrophy and hyperlipidaemia during myocardial infarction in rats. Metabolism, 62, 52–61.CrossRefPubMed Kannan, M. M., & Quine, D. S. (2013). Ellagic acid inhibits cardiac arrhythmias, hypertrophy and hyperlipidaemia during myocardial infarction in rats. Metabolism, 62, 52–61.CrossRefPubMed
31.
go back to reference Grobe, J. L., Mecca, A. P., Mao, H., & Katovich, M. G. (2006). Chronic angiotensin (1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension. American Journal of Physiology: Heart and Circulation Physiology, 290, 2417–2423. Grobe, J. L., Mecca, A. P., Mao, H., & Katovich, M. G. (2006). Chronic angiotensin (1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension. American Journal of Physiology: Heart and Circulation Physiology, 290, 2417–2423.
32.
go back to reference Border, W. A., & Noble, N. A. (1994). Transforming growth factor β in tissue fibrosis. New England Journal of Medicine, 331, 1286–1292.CrossRefPubMed Border, W. A., & Noble, N. A. (1994). Transforming growth factor β in tissue fibrosis. New England Journal of Medicine, 331, 1286–1292.CrossRefPubMed
33.
go back to reference Roy, S. G., & Prince, S. M. (2013). Protective effects of sinapic acid on cardiac hypertrophy, dyslipidaemia and altered electrocardiogram in isoproterenol-induced myocardial infarcted rats. European Journal of Pharmacology, 699, 213–218.CrossRefPubMed Roy, S. G., & Prince, S. M. (2013). Protective effects of sinapic acid on cardiac hypertrophy, dyslipidaemia and altered electrocardiogram in isoproterenol-induced myocardial infarcted rats. European Journal of Pharmacology, 699, 213–218.CrossRefPubMed
34.
go back to reference Becker, L. B. (2004). New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovascular Research, 61, 461–470.CrossRefPubMed Becker, L. B. (2004). New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovascular Research, 61, 461–470.CrossRefPubMed
35.
go back to reference Ito, M., Murakami, K., & Yoshino, M. (2005). Antioxidant action of eugenol compounds: Role of metal ion in the inhibition of lipid peroxidation. Food and Chemical Toxicology, 43, 461–466.CrossRefPubMed Ito, M., Murakami, K., & Yoshino, M. (2005). Antioxidant action of eugenol compounds: Role of metal ion in the inhibition of lipid peroxidation. Food and Chemical Toxicology, 43, 461–466.CrossRefPubMed
Metadata
Title
Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat
Authors
Kais Mnafgui
Raouf Hajji
Fatma Derbali
Anis Gammoudi
Gaddour Khabbabi
Hedi Ellefi
Noureddine Allouche
Adel Kadri
Neji Gharsallah
Publication date
01-10-2016
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 4/2016
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-015-9343-x

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