Skip to main content
PMC home page
Indian Journal of Clinical Biochemistry logoLink to Indian Journal of Clinical Biochemistry
. 2006 Sep;21(2):107–113. doi: 10.1007/BF02912923

Prevention of isoproterenol-induced cardiac hypertrophy by eugenol, an antioxidant

Rashmi Choudhary 1, K P Mishra 2, C Subramanyam 1,✉
PMCID: PMC3453984  PMID: 23105625

Abstract

Recent reports on the involvement of calcineurin in cardiac hypertrophy and its susceptibility to free radicals, prompted us to examine possible beneficial effects of dietary antioxidants in this regard. In continuation of initialin vitro studies revealing eugenol to be a potent calcineurin inhibitor, we investigated its ability to reverse isoproterenol-induced cardiac hypertrophy in rats. Intraperitoneal administration of isoproterenol (1 mg/kg body wt/day for 10 days) induced cardiac hypertrophy with increased heart weight and enhanced apoptosis of myocytes concomitant with accumulation of reactive oxygen species, decreased glutathione contents, increased activities of calcineurin and protein kinase C in ventricular tissue. Administering eugenol for 3 days (1 mg/kg body wt/twice a day), followed by combined administration of isoproterenol and eugenol resulted in significant reversal of cardiac hypertrophy and restoration of above changes. These results suggest that eugenol, a natural antioxidant of dietary origin, may offer potential benefits in the management of cardiac hypertrophy.

Key Words: Antioxidants, Calcineurin activity, Cardiac hypertrophy, Eugenol, ROS, Isoproterenol

Full Text

The Full Text of this article is available as a PDF (92.4 KB).

References

  • 1.Braun M., Simonis G., Birkner K., Pauke B., Strasser R.H. Regulation of protein kinase C isozyme and calcineurin expression in isoproterenol induced cardiac hypertrophy. J. Cardiovasc. Pharmacol. 2003;41:946–954. doi: 10.1097/00005344-200306000-00018. [DOI] [PubMed] [Google Scholar]
  • 2.Cao Z., Tsang M., Zhao H., Li Y. Induction of endogenous antioxidants and phase 2 enzymes by a-lipoic acid in rat cardiac H9C2 cells: protection against oxidative injury. Biochem. Biophys. Res. Commun. 2003;310:979–985. doi: 10.1016/j.bbrc.2003.09.110. [DOI] [PubMed] [Google Scholar]
  • 3.Chattopadhyay A., Biswas S., Bandyopadhyay D., Sarkar C., Datta A. G. Effect of isoproterenol on lipid peroxidation and antioxidant enzymes of myocardial tissue of mice and protection by quinidine. Mol. Cell. Biochem. 2003;245:43–49. doi: 10.1023/A:1022808224917. [DOI] [PubMed] [Google Scholar]
  • 4.FAO (1982) Evaluation of certain food additives and contaminants. Technical Report Series No. 20. FAO/WHO Expert Committee on food additives.
  • 5.Hissin P.J., Hilf R. A fluorimetric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 1976;74:214–226. doi: 10.1016/0003-2697(76)90326-2. [DOI] [PubMed] [Google Scholar]
  • 6.Huang Y.C., Wu B.N., Lin Y.T., Chen S.J., Chiu C.C., Cheng C.J., Chen I.J. Eugenodilol: a third-generation beta-adrenoceptor blocker, derived from eugenol, with alpha-adrenoceptor blocking and beta2-adrenoceptor agonist-associated vasorelaxant activities. J. Cardiovasc. Pharmacol. 1999;34:10–20. doi: 10.1097/00005344-199907000-00003. [DOI] [PubMed] [Google Scholar]
  • 7.Jayashree T., Subramanyam C. Antiaflatoxigenic activity of eugenol is due to inhibition of lipid peroxidation. Lett. Appl Microbiol. 1999;28:179–183. doi: 10.1046/j.1365-2672.1999.00512.x. [DOI] [PubMed] [Google Scholar]
  • 8.Kang Y.J., Zhou Z.X., Wu H., Wang G.W., Saari J.T., Klein J.B. Metallothionein inhibits myocardial apoptosis in copper-deficient mice: role of atrial natriuretic peptide. Lab. Invest. 2000;80:745–757. doi: 10.1038/labinvest.3780078. [DOI] [PubMed] [Google Scholar]
  • 9.Leinwand L.A. Calcineurin inhibition and cardiac hypertrophy: A matter of balance. Proc. Natl. Acad. Sci. USA. 2001;98:2947–2949. doi: 10.1073/pnas.051033698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Lin Y.T., Wu B.N., Horng C.F., Huang Y.C., Hong S.J., Lo Y.C., Cheng C.J., Chen I.J. Isoeugenolol: A selective beta 1-drenergic antagonist with tracheal and vascular smooth muscle relaxant properties. Jpn. J. Pharmacol. 1999;80:127–136. doi: 10.1254/jjp.80.127. [DOI] [PubMed] [Google Scholar]
  • 11.Lipkin G.W., Tucker B., Giles M., Raine A.E. Ambulatory blood pressure and left ventricular mass in cyclosporin and not cyclosporin treated renal transplant recipients. J. Hypertens. 1993;11:439–442. doi: 10.1097/00004872-199304000-00015. [DOI] [PubMed] [Google Scholar]
  • 12.Marklund S., Marklund G. Involvement of the superoxide anion radical in the auto oxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 1974;47:469–474. doi: 10.1111/j.1432-1033.1974.tb03714.x. [DOI] [PubMed] [Google Scholar]
  • 13.Martinez J.I.R., Launay J.M., Dreux C. A sensitive flourimetric microassay for glutathione peroxidase activity. Application to human blood platelets. Anal. Biochem. 1979;98:154–159. doi: 10.1016/0003-2697(79)90720-6. [DOI] [PubMed] [Google Scholar]
  • 14.Meguro T., Hong C., Asai K., Takagi G., McKinsey T.A., Olson E.N., Vatner S.F. Cyclosporine attenuates pressure overload hypertrophy in mice while enhancing susceptibility to decompensation and heart failure. Circ. Res. 1999;84:735–740. doi: 10.1161/01.res.84.6.735. [DOI] [PubMed] [Google Scholar]
  • 15.Miyashita T., Takeishi Y., Takahashi H., Kato S., Kubota I., Tomoike H. Role of calcineurin in insulin-like growth factor-1-induced hypertrophy of cultured adult rat ventricular myocytes. Jpn. Circ. J. 2001;65:815–819. doi: 10.1253/jcj.65.815. [DOI] [PubMed] [Google Scholar]
  • 16.Molkentin J., Lu J., Antos C., Markham B., Richardson J., Robbins J., Grant S., Olson E.N. A calcineurin dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998;93:215–228. doi: 10.1016/S0092-8674(00)81573-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Molkentin J.D. Calcineurin and beyond: Cardiac hypertrophy signaling. Circ. Res. 2000;87:731–738. doi: 10.1161/01.res.87.9.731. [DOI] [PubMed] [Google Scholar]
  • 18.Nagata K., Somura F., Obata K., Odashima M., Izawa H., Ichihara S., Nagasaka T., Iwase M., Yamada Y., Nakashima N., Yokota M. AT1 receptor blockade reduces cardiac calcineurin activity in hypertensive rats. Hypertension. 2002;40:168–74. doi: 10.1161/01.HYP.0000026668.50222.1E. [DOI] [PubMed] [Google Scholar]
  • 19.Padma S., Subramanyam C. Extracellular calcineurin: Identification and quantitation in serum and amniotic fluid. Clin. Biochem. 1999;32:491–494. doi: 10.1016/S0009-9120(99)00049-1. [DOI] [PubMed] [Google Scholar]
  • 20.Pandey, B.N. and Mishra, K.P. (2003) Modification of thymocytes membrane radio-oxidative damage and apoptosis by eugenol. J. Environ. Pathol. Toxicol. Oncol. in Press; [DOI] [PubMed]
  • 21.Saccani S., Saccani A., Varesio L., Ghosh P., Young H.A., Sica A. Divergent effects of dithiocarbamates on AP-1-containing and AP-1-less NFAT sites. Eur. J. Immunol. 1999;29:1194–1201. doi: 10.1002/(SICI)1521-4141(199904)29:04<1194::AID-IMMU1194>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  • 22.Sawyer D.B., Siwik D.A., Xiao L., Pimentel D.R., Singh K., Colucci W.S. Role of oxidative stress in myocardial hypertrophy and failure. J. Mol. Cell. Cardiol. 2002;34:379–379. doi: 10.1006/jmcc.2002.1526. [DOI] [PubMed] [Google Scholar]
  • 23.Sharma J.N., Srivastava K.C., Gan E.K. Suppressive effects of eugenol and ginger oil on arthritic rats. Pharmacology. 1994;49:314–318. doi: 10.1159/000139248. [DOI] [PubMed] [Google Scholar]
  • 24.Shizukuda Y., Buttrick P.M., Geenen D.L., Borczuk A.C., Kitsis R.N., Sonnenblick E.H. beta-adrenergic stimulation causes cardiocyte apoptosis: influence of tachycardia and hypertrophy. Am. J. Physiol. 1998;275:H961–H968. doi: 10.1152/ajpheart.1998.275.3.H961. [DOI] [PubMed] [Google Scholar]
  • 25.Snedecor G.W., Cochran W.G. Shortcut and non-parametric methods. In: Snedecor G.W., Cochran W.G., editors. Statistical methods. New Delhi: Oxford and IBH; 1986. pp. 120–132. [Google Scholar]
  • 26.Sugden P.H. Signalling pathways in cardiac myocyte hypertrophy. Ann. Med. 2001;33:611–622. [PubMed] [Google Scholar]
  • 27.Terzian A.R., Rubin R.P. Translocation of the á-isozyme of protein kinase C during stimulation of rat parotid acinar cells by phorbol ester and carbachol. Archives. Oral. Biol. 1993;38:1051–1056. doi: 10.1016/0003-9969(93)90166-J. [DOI] [PubMed] [Google Scholar]
  • 28.Wang X., Culotta V.C., Klee C.B. Superoxide dismutase protects calcineurin from inactivation. Nature. 1996;383:434–437. doi: 10.1038/383434a0. [DOI] [PubMed] [Google Scholar]
  • 29.Zou Y., Yao A., Zhu W., Kudoh S., Hiroi Y., Shimoyama M., Uozumi H., Kohmoto O., Takahashi T., Shibasaki F., Nagai R., Yazaki Y., Komuro I. Isoproterenol activates extracellular signal-regulated protein kinases in cardiomyocytes through calcineurin. Circulation. 2001;104:102–108. doi: 10.1161/hc2601.090987. [DOI] [PubMed] [Google Scholar]

Articles from Indian Journal of Clinical Biochemistry are provided here courtesy of Springer

RESOURCES