Top

Published in:

01-12-2011

N-acetylcysteine Offers Cardioprotection by Decreasing Cardiac Lipid Hydroperoxides and 8-Isoprostane Level in Isoproterenol-Induced Cardiotoxicity in Rats

Authors: Nagaraja Haleagrahara, Varkkey Julian, Srikumar Chakravarthi

Published in: Cardiovascular Toxicology | Issue 4/2011

Abstract

This study investigated the cardioprotective effect of N-acetylcysteine (NAC) on isoproterenol (ISO)-induced cardiotoxicity in rats. Male Sprague–Dawley rats were divided into control, NAC alone (100 mg/kg BW orally for 14 days), ISO-control (85 mg/kg BW), and ISO with NAC (for 14 days). Serum creatine kinase-MB and Lactate dehydrogenase were measured. From the heart homogenate lipid hydroperoxides (LPO), superoxide dismutase (SOD), total glutathione (GSH), and 8-isoprostane (IP) were measured. Histopathological examination of the heart was also carried out. There was a significant increase (P < 0.05) in LPO and IP levels in ISO-control group and NAC treatment reduced these changes. Antioxidant enzyme, SOD and GSH, level decreased significantly (P < 0.05) in ISO-control group, and treatment with NAC was able to reverse these changes significantly (P < 0.05). Histopathologically, ISO-control group showed morphological changes suggestive of cardiotoxicity with large areas of coagulative necrosis, with diffused interstitial edema. NAC treatment successfully reduced these histopathological changes. In conclusion, the study proves that NAC has a strong cardioprotective effect against isoproterenol-induced cardiac changes. NAC decreases isoproterenol-induced LPO and IP levels in the heart tissue and prevented free radicals–induced damage to the myocardium.

Lopez, A. D., & Murrau, C. C. (1998). The global burden disease, 1990–2020. Nature Medicine, 4, 1241–1243.PubMedCrossRef

Towbin, J. A. (2001). Molecular genetic basis of sudden cardiac death. Cardiovascular Pathology, 10, 283–295.PubMedCrossRef

Smith, G. D., Shipley, M. J., Marmot, M. G., & Rose, G. (1992). Plasma cholesterol concentration and mortality. The Whitehall study. The Journal of the American Medical Association, 267, 70–76.CrossRef

Thygesen, K., Alpert, J. S., & White, H. D. (2007). Universal definition of myocardial infarction. Journal of American College of Cardiology, 50, 2173–2195.CrossRef

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.CrossRef

Libby, P. (2001). Current concepts of pathogenesis of the acute coronary syndromes. Circulation, 104, 365–372.PubMed

Lilly, L. S. (2006). Pathophysiology of heart disease: A collaborative project of medical students and faculty (4th ed., pp. 131–184). Baltimore, MD: Lippincott Williams & Wilkins.

Ferrari, R., Alfieri, O., Curello, S., Ceconi, C., Cargnoni, A., & Marzollo, P. (1990). Occurrence of oxidative stress during reperfusion of the human heart. Circulation, 81, 201–211.PubMedCrossRef

Lefer, D. J., & Grabger, D. N. (2000). Oxidative stress and cardiac disease. American Journal of Medicine, 109, 315–323.PubMedCrossRef

10.

Zhou, R., Xu, Q., Zheng, P., Yan, L., Zheng, J., & Dai, G. (2008). Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. European Journal of Pharmacology, 586, 244–250.PubMedCrossRef

11.

Lawson, J. S., Rokach, J., & Fitzgerald, G. A. (1999). Isoprostanes: Formation, analysis and sue as indices of lipid peroxidation in vivo. The Journal of Biological Chemistry, 274, 24441–24444.PubMedCrossRef

12.

Cracowski, J. L., Durand, T., & Bessard, G. (2002). Isoprostanes as a biomarker of lipid peroxidation in humans: Physiology, pharmacology, and clinical implications. Trends in Pharmacological Sciences, 23, 360–366.PubMedCrossRef

13.

Morrow, J. D., & Roberts, L. J. (1996). The isoprostanes. Current knowledge and directions for future research. Biochemical Pharmacology, 51, 1–9.PubMedCrossRef

14.

Rajadurai, M., Mainzen, S., & Prince, P. (2006). Preventive effect of naringin on lipids, lipoproteins and lipid metabolic enzymes in isoproterenol-induced myocardial infarction in Wistar rats. Journal of Biochemical and Molecular Toxicology, 20, 191–197.PubMedCrossRef

15.

Rathore, N., John, S., Kale, M., & Bhatnagar, D. (1998). Lipid peroxidation and antioxidant enzymes in isoproterenol-induced oxidative stress in rat tissues. Pharmacological Research, 38, 297–303.PubMedCrossRef

16.

Arstall, M. A., Yang, J., Stafford, I., Betts, H., & Horowitz, J. D. (1995). N-acetylcysteine in combination with nitroglycerin and streptokinase for the treatment of evolving myocardial infarction. Circulation, 92, 2855–2862.PubMed

17.

Kerksick, C., & Willoughby, D. (2005). The antioxidant role of glutathione and N-acetylcysteine supplements and exercise-induced oxidative stress. The Journal of the International Society of Sports Nutrition, 2, 38–44.CrossRef

18.

Keles, M. S., Demirci, N., Yildirim, A., Atamanalp, S. S., & Altinkaynak, K. (2008). Protective effects of N-acetylcysteine and Ginkgo biloba extract on ischaemia-reperfusion-induced hepatic DNA damage in rats. Clinical and Experimental Medicine, 8, 193–198.PubMedCrossRef

19.

Banerjee, S. K., Sood, S., Dinda, A. K., Das, T. K., & Maulik, S. K. (2003). Chronic oral administration of raw garlic protects against isoproterenol-induced myocardial necrosis in rat. Comparative Biochemistry Physiology Toxicology Pharmacology, 136, 377–386.CrossRef

20.

Krenek, P., Kmecova, J., Kucerova, D., Bajuszova, Z., Musil, P., & Gazova, A. (2009). Isoproterenol-induced heart failure in the rat is associated with nitric oxide-dependent functional alterations of cardiac function. European Journal of Heart Failure, 11, 140–146.PubMedCrossRef

21.

Fozzard, H. A. (1975). Validity of myocardial infarction model. Circulation, 52, 131–146.

22.

Panda, V. S., & Naik, S. R. (2008). Cardioprotective activity of Ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: A biochemical and histoarchitectural evaluation. Experimental and Toxicologic Pathology, 60, 397–404.PubMedCrossRef

23.

Grimm, D., Elsner, D., Schunkert, H., Pfeifer, M., Griese, D., Bruckschlegel, G., et al. (1998). Development of heart failure following isoproterenol administration in the rat: Role of the renin-angiotensin system. Cardiovascular Research, 37, 91–100.PubMedCrossRef

24.

Senthil, S., Sridevi, M., & Pugalendi, K. V. (2007). Cardioprotective effect of oleanolic acid on isoproterenol-induced myocardial ischemia in rats. Toxicologic Pathology, 35, 418–423.PubMedCrossRef

25.

Liu, B., Li, W., Li, Y., Wang, Z., Li, H., Liu, P., et al. (2009). Protective effects of N-acetylcysteine in isoproterenol-induced myocardium injury in rats. Molecular Biology Reports, 36, 761–765.PubMedCrossRef

26.

Nagoor Meeran, M. F., & Mainzen Prince, P. S. (2011). Protective effects of N-acetylcysteine on lipid peroxide metabolism on isoproterenol-induced myocardial infarcted rats. Journal of Biochemical and Molecular Toxicology, 25, 151–157.PubMedCrossRef

27.

Pinelli, A., Trivulzio, S., Tomasoni, L., Brenna, S., Bonacina, E., & Accinni, R. (2004). Isoproterenol-induced myocardial infarction in rabbits Protection by propanolol or labetolol: A proposed non-invasive procedure. The European Journal of Pharmaceutical Sciences, 23, 277–285.

28.

Wang, S. B., Tian, S., Yang, F., Yang, H. G., Yang, X. Y., & Du, G. H. (2009). Cardioprotective effect of salvianolic acid—A on isoproterenol-induced myocardial infarction in rats. European Journal of Pharmacology, 615, 125–132.PubMedCrossRef

29.

Peer, P. A., Trivedi, P. C., Nigade, P. B., Ghaisas, M. M., & Deshpande, A. D. (2008). Cardioprotective effect of Azadirachta indica A. Juss. On isoprenaline induced myocardial infarction in rats. International Journal of Cardiology, 126, 123–126.PubMedCrossRef

30.

Upaganlawar, A., Gandhi, C., & Balaraman, R. (2009). Effect of green tea and vitamin E combination in Isoproterenol-induced myocardial infarction in rats. Plant Foods and Human Nutrition, 64, 75–80.CrossRef

31.

Wittstein, I. S., Thiermann, D. R., Lima, J. A. C., Baughman, K. L., Schulman, S. P., & Gerstenblith, G. (2005). Neurohumoral features of myocardial stunning due to sudden emotional stress. New England Journal of Medicine, 352, 539–548.PubMedCrossRef

32.

Bolli, R., & Marbán, E. (1999). Molecular and cellular mechanisms of myocardial stunning. Physiological Reviews, 79, 609–634.PubMed

33.

Dikshit, M., Van Oosten, M. H., de Graff, S., & Srimal, R. C. (1992). Free radical scavenger mechanisms in experimentally induced ischemia in the rabbit heart and protective effect of verapamil. Archives of International Pharmacodynamics Therapy, 318, 55–65.

34.

Remiao, F., Carmo, H., Carcalho, F. D., & Bastos, M. L. (2000). Inhibition of glutathione reductase by isoproterenol-induced oxidation products. Journal of Enzyme Inhibition and Medicinal Chemistry, 15, 47–61.

35.

Mathew, S., Menon, P. V. G., & Kurup, P. A. (1978). Changes in myocardial and aortic lipids, lipolytic activity and fecal excretion of sterols and bile acids in isoproterenol-induced myocardial infarction in rats. Indian Journal Biochemistry, 18, 131–133.

36.

Bloom, S., & Davis, D. L. (1972). Calcium as mediator of isoproterenol-induced myocardial necrosis. American Journal of Pathology, 69, 459–470.PubMed

37.

Boucher, M., Pesant, S., Lei, Y. H., Nanton, N., Most, P., & Eckhart, A. D. (2008). Simultaneous administration of insulin-like growth factor-1 and darbepoetin alfa protects the rat myocardium against myocardial infarction and enhances angiogenesis. Clinical and Translational Science, 1, 13–20.PubMedCrossRef

38.

Montuschi, P., Ciabattoni, G., Paredi, P., du Bois, R. M., Pantelidis, P., Kharitonov, S. A., et al. (1998). 8-Isoprostane as a biomarker of oxidative stress in interstitial lung disease. American Journal Respiratory Critical Care Medicine, 158, 1524–1527.

39.

Maier, C. M., & Chan, P. H. (2002). Book review: Role of superoxide dismutases in oxidative damage and neurodegenerative disorders, vol. 8, issue no. 4. Beverley Hills: Sage.

40.

Bolli, R. (1990). Mechanism of myocardial stunning. Circulation, 82, 723–738.PubMedCrossRef

41.

Dickey, D. T., Muldoon, L. L., Doolittle, N. D., Peterson, D. R., Kraemer, D. F., & Neuwelt, E. A. (2008). Effect of N-acetylcysteine route of administration on chemoprotection against cisplatin-induced toxicity in rat models. Cancer Chemotherapy and Pharmacology, 62, 235–241.PubMedCrossRef

42.

Suke, S. G., Ahmed, R. S., Pathak, R., Tripathi, A. K., & Banerjee, B. D. (2008). Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine. Brazilian Journal of Medicine Biology Research, 41, 765–768.

43.

44.

Basha, R. H., Priscilla, D. H. (2011). An in vivo and in vitro study on the protective effects of N-acetylcysteine on mitochondrial dysfunction in isoproterenol treated myocardial infarcted rats. Experimental and Toxicologic Pathology, 3 Jun 2011 [Epub ahead of print].

45.

Decaro, L., Ghizzi, A., & Costa, R. (1989). Pharmacokinetics and bioavailability of oral acetylcysteine in healthy volunteers. Arzneimittel Forchung, 39, 382–385.

46.

Abe, M., Takiguchi, Y., Ichimaru, S., Tsuchiya, K., & Wada, K. (2008). Comparison of the protective effect of N-acetylcysteine by different treatments on rat myocardial ischemia-reperfusion injury. Journal of Pharmacological Sciences, 106, 571–577.PubMedCrossRef

47.

Finkel, M. S., Shen, L., Oddis, C. V., Romeo, R. C., & Salama, G. (1993). Positive inotropic effect of acetylcysteine in cardiomyopathic Syrian hamsters. Journal of Cardiovascular Pharmacology, 21, 29–34.PubMedCrossRef

48.

Zaidi, N. F., Lagenaur, C. F., Abramson, J. J., Pessah, I., & Salama, G. (1989). Reactive disulfides trigger Ca2+ release from sarcoplasmic reticulum via an oxidation reaction. Journal of Biological Chemistry, 264, 21725–21736.PubMed

Title: N-acetylcysteine Offers Cardioprotection by Decreasing Cardiac Lipid Hydroperoxides and 8-Isoprostane Level in Isoproterenol-Induced Cardiotoxicity in Rats
Authors: Nagaraja Haleagrahara
Varkkey Julian
Srikumar Chakravarthi
Publication date: 01-12-2011
Publisher: Humana Press Inc
Published in: Cardiovascular Toxicology / Issue 4/2011
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-011-9132-0

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Keynote webinar | Spotlight on medication adherence

Springer Medicine

N-acetylcysteine Offers Cardioprotection by Decreasing Cardiac Lipid Hydroperoxides and 8-Isoprostane Level in Isoproterenol-Induced Cardiotoxicity in Rats

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2011

Infrasound Exposure Induces Apoptosis of Rat Cardiac Myocytes by Regulating the Expression of Apoptosis-Related Proteins

Supplemental Studies for Cardiovascular Risk Assessment in Safety Pharmacology: A Critical Overview

Cyclooxygenase-2-Derived Prostacyclin Protective Role on Endotoxin-Induced Mouse Cardiomyocyte Mortality

Carbon Monoxide Pollution Impairs Myocardial Perfusion Reserve: Implication of Coronary Endothelial Dysfunction

Role of COX-2 in the Bioactivation of Methylenedianiline and in Its Proliferative Effects in Vascular Smooth Muscle Cells

Electrocardiographic Characterization of Rhesus Monkey Model of Ischemic Myocardial Infarction Induced by Left Anterior Descending Artery Ligation

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page