Skip to main content
SpringerLink
Log in

Caffeic acid protects rat heart mitochondria against isoproterenol-induced oxidative damage

  • Original Paper
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

Cardiac mitochondrial dysfunction plays an important role in the pathology of myocardial infarction. The protective effects of caffeic acid on mitochondrial dysfunction in isoproterenol-induced myocardial infarction were studied in Wistar rats. Rats were pretreated with caffeic acid (15 mg/kg) for 10 days. After the pretreatment period, isoproterenol (100 mg/kg) was subcutaneously injected to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed considerable increased levels of serum troponins and heart mitochondrial lipid peroxidation products and considerable decreased glutathione peroxidase and reduced glutathione. Also, considerably decreased activities of isocitrate, succinate, malate, α-ketoglutarate, and NADH dehydrogenases and cytochrome-C-oxidase were observed in the mitochondria of myocardial-infarcted rats. The mitochondrial calcium, cholesterol, free fatty acids, and triglycerides were considerably increased and adenosine triphosphate and phospholipids were considerably decreased in isoproterenol-induced rats. Caffeic acid pretreatment showed considerable protective effects on all the biochemical parameters studied. Myocardial infarct size was much reduced in caffeic acid pretreated isoproterenol-induced rats. Transmission electron microscopic findings also confirmed the protective effects of caffeic acid. The possible mechanisms of caffeic acid on cardiac mitochondria protection might be due to decreasing free radicals, increasing multienzyme activities, reduced glutathione, and adenosine triphosphate levels and maintaining lipids and calcium. In vitro studies also confirmed the free-radical-scavenging activity of caffeic acid. Thus, caffeic acid protected rat’s heart mitochondria against isoproterenol-induced damage. This study may have a significant impact on myocardial-infarcted patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  • Alpert JS, Thygesan K, Antman E, Bassand JP (2000) Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 36:959–969

    Article  PubMed  CAS  Google Scholar 

  • Bakan E, Taysi S, Polat MF (2002) Nitric oxide levels and lipid peroxidation in plasma of patients with gastric cancer. Jpn J Clin Oncol 32:162–166

    Article  PubMed  Google Scholar 

  • Bel Chenko DI, Sopka NV, Kalinkin MN, Khanina NIA, Chelnokov VS (1990) The metabolic changes in myocardial subcellular fractions in the pathogenesis of ischemic heart disease. Patol Fiziol Eksp Ter 2:16–20

    Google Scholar 

  • Bertinchant JP, Robert E, Polge A, Marty-Double C, Fabbro-Peray P, Poirey S, Aya G, Juan JM, Ledermann B, De la Coussaye JE, Dauzat M (2000) Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats. Clin Chim Acta 298:13–28

    Article  PubMed  CAS  Google Scholar 

  • Castellari M, Sartini E, Fabiani A, Arfelli G, Amati A (2002) Analysis of wine phenolics by high performance liquid chromatography using a monolithic type column. J Chromatogr A 973:221–227

    Article  PubMed  CAS  Google Scholar 

  • Chagoya de Sanchez V, Hernandez-Munoz R, Lopez Barrera F, Yanez L, Vidrio S, Suarez J, Cota-Garza MD, Aranda-Fraustro A, Cruz D (1997) Sequential changes of energy metabolism and mitochondrial function in myocardial infarction induced by isoproterenol in rats: a long-term and integrative study. Can J Physiol Pharmacol 75:1300–1311

    Article  PubMed  CAS  Google Scholar 

  • De Bono DP, Boon NA (1992) Diseases of the cardiovascular system. In: Edwards CRW, Boucheir IAD (eds) Davidson’s Principles and Practice of Medicine. Churchill Livingstone, Hong Kong, pp 249–340

    Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  PubMed  CAS  Google Scholar 

  • Falholt K, Lund B, Falholt W (1973) An easy colorimetric micromethod for routine determination of free fatty acids in plasma. Clin Chim Acta 46:105–111

    Article  PubMed  CAS  Google Scholar 

  • Folch J, Lees M, Sloane SGH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509

    PubMed  CAS  Google Scholar 

  • Fossati P, Prencipe L (1982) Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28:2077–2080

    PubMed  CAS  Google Scholar 

  • Fraga CG, Leibovitz BE, Tappel AL (1988) Lipid peroxidation measured as thiobarbituric acid reactive substances in tissue slices: characterization and comparison with homogenate and microsomes. Free Radic Biol Med 4:155–161

    Article  PubMed  CAS  Google Scholar 

  • Gilski DJ, Borkenhagen B (2005) Risk evaluation for cardiovascular health. Crit Care Nurse 25:26–28

    PubMed  Google Scholar 

  • Gulcin I (2006) Antioxidant activity of caffeic acid. Toxicology 217:213–220

    Article  PubMed  CAS  Google Scholar 

  • Gupta S, De Lemos JA (2007) Use and misuse of cardiac troponins in clinical practice. Prog Cardiovasc Dis 50:151–165

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JM (1990) Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 186:1–85

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JM, Aruoma OI (1987) The deoxyribose methods: a simple ‘test tube’ assay for determination of rate constants for reactions of hydroxyl radicals. Anal Biochem 165:215–219

    Article  PubMed  CAS  Google Scholar 

  • Harada K, Fukata Y, Miwa A, Kaneta S, Fukushima H, Ogawa N (1993) Effect of KRN 2391, a novel vasodilator, on various experimental anginal models in rats. Jpn J Pharmacol 63:35–39

    Article  PubMed  CAS  Google Scholar 

  • Herrmann K (1976) Flavonols and flavones in food plants: a review. J Food Technol 11:433–438

    Article  CAS  Google Scholar 

  • Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low-density lipoprotein. Anal Biochem 202:384–389

    Article  PubMed  CAS  Google Scholar 

  • Karthikeyan K, Sarala Bai BR, Niranjali Devaraj S (2007) Grape seed proanthocyanidins ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes: an in vivo study. Life Sci 81:1615–1621. doi:10.1016/jlfs.2007.09.033

    Article  PubMed  CAS  Google Scholar 

  • King J (1965) Isocitrate dehydrogenase. In: King JC, Van D (eds) Practical clinical enzymology. Nostrand Co, London, p 363

    Google Scholar 

  • Kono Y, Kobayashi K, Tagawa S, Adachi K, Ueda A, Sawa Y, Shibata H (1997) Antioxidant activity of polyphenolics in diets: rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen. Biochim Biophys Acta 1335:335–342

    PubMed  CAS  Google Scholar 

  • Lie JT, Pairolero PC, Holley KE, Titus JL (1975) Macroscopic enzyme-mapping verification of large, homogeneous, experimental myocardial infarcts of predictable size and location in dogs. J Thorac Cardiovasc Surg 69:599–605

    PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin’s-phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  • Manjula TS, Devi CS (1993) Effect of aspirin on mitochondrial lipids in experimental myocardial infarction in rats. Biochem Mol Biol Int 29:921–928

    PubMed  CAS  Google Scholar 

  • Mattila P, Kumpulainen J (2002) Determination of free and total phenolic acids in plant-derived foods by high performance liquid chromatography with diode-array detection. J Agric Food Chem 50:3660–3667

    Article  PubMed  CAS  Google Scholar 

  • Mehler AH, Kornberg A, Grisolia S, Ochoa S (1948) The enzymatic mechanims of oxidation-reductions between malate or isocitrate or pyruvate. J Biol Chem 174:961–977

    PubMed  CAS  Google Scholar 

  • Minakami S, Ringler RL, Singer TP (1962) Studies on the respiratory chain-linked dihydro diphospho pyridine nucleotide dehydrogenase I: assay of the enzyme in particulate and in soluble preparations. J Biol Chem 237:569–576

    PubMed  CAS  Google Scholar 

  • Murray AJ, Edwards LM, Clarke K (2007) Mitochondria and heart failure. Curr Opin Clin Nutr Metab Care 10:704–711

    Article  PubMed  CAS  Google Scholar 

  • Nardini M, D’Aquino M, Tomassi G, Gentili V, Di Felice M, Scaccini C (1995) Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxy cinnamic acid derivatives. Free Radic Biol Med 19:541–552

    Article  PubMed  CAS  Google Scholar 

  • National Research Council (1996) Carcinogens and anticarcinogens in the human diet. National Academy, Washington

    Google Scholar 

  • Nishikimi M, Appaji N, Yagi K (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Comm 46:849–853

    Article  PubMed  CAS  Google Scholar 

  • Pearl W, Cascarano J, Zweifach BW (1963) Microdetermination of cytochrome oxidase in rat tissues by the oxidation on N-phenyl-p-phenylene diamine or ascorbic acid. J Histochem Cytochem 11:102–104

    CAS  Google Scholar 

  • Prabhu SD, Chandrasekar B, Murray DR, Freeman GL (2000) Beta-adrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling. Circulation 101:2103–2109

    PubMed  CAS  Google Scholar 

  • Prabhu S, Jainu M, Sabitha KE, Devi CS (2006a) Role of mangiferin on biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats. J Ethnopharmacol 107:126–133

    Article  CAS  Google Scholar 

  • Prabhu S, Jainu M, Sabitha KE, Shyamala Devi CS (2006b) Effect of mangiferin on mitochondrial energy production in experimentally induced myocardial infarcted rats. Vascul Pharmacol 44:519–525. doi:10.1016/j.vph.2006.03.012

    Article  CAS  Google Scholar 

  • Psotova J, Lasovsky J, Vicar J (2003) Metal-chelating properties, electrochemical behavior, scavenging and cytoprotective activities of six natural phenolics. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 147:147–153

    PubMed  CAS  Google Scholar 

  • Reed LJ, Mukherjee RB (1969) Alpha ketoglutarate dehydrogenase complex from Escherichia coli. In: Lowenstein JM (ed) Methods in enzymology. Academic, London, pp 53–61

    Google Scholar 

  • Richter C, Park JW, Ames BN (1988) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci U S A 85:6465–6467

    Article  PubMed  CAS  Google Scholar 

  • Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590

    Article  PubMed  CAS  Google Scholar 

  • Sabeena Farvin KH, Anandan R, Kumar SH, Shiny KS, Sankar TV, Thankappan TK (2004) Effect of squalene on tissue defense system in isoproterenol-induced myocardial infarction in rats. Pharmacol Res 50:231–236. doi:10.1016/j.phrs.2004.03.004

    Article  PubMed  CAS  Google Scholar 

  • Sangeetha T, Darlin Quine S (2009) Preventive effect of S-allyl cysteine sulphoxide (Alliin) on mitochondrial dysfunction in normal and isoproterenol induced cardio toxicity in male Wistar rats: a histopathological study. Mol Cell Biochem 328:1–8

    Article  PubMed  CAS  Google Scholar 

  • Sathish V, Ebenezar KK, Devaki T (2003) Biochemical changes on the cardioprotective effect of nicorandil and amlodipine during experimental myocardial infarction in rats. Pharmacol Res 48:565–570

    Article  PubMed  CAS  Google Scholar 

  • Senthil Kumaran K, Stanely Mainzen Prince P (2010) Protective effect of coffee acid on cardiac markers and lipid peroxide metabolism in cardiotoxic rats: an in vivo and in vitro study. Metabol Clin Exp. doi:10.1016/j.metabol.2009.11.010

  • Sivakumar R, Anandh Babu PV, Shyamaladevi CS (2008) Protective effect of aspartate and glutamate on cardiac mitochondrial function during myocardial infarction in experimental rats. Chem Biol Interact 176:227–233

    Article  PubMed  CAS  Google Scholar 

  • Slater EC, Borner WD Jr (1952) The effect of fluoride on the succinic oxidase system. Biochem J 52:185–196

    PubMed  CAS  Google Scholar 

  • Starkov AA, Polster BM, Fiskum G (2002) Regulation of hydrogen peroxide production by brain mitochrondria by calcium and Bax. J Neurochem 83:220–228

    Article  PubMed  CAS  Google Scholar 

  • Suchalatha S, Thirugnanasambandam P, Maheswaran E, Shyamala Devi CS (2004) Role of Arogh, a polyherbal formulation to mitigate oxidative stress in experimental myocardial infarction. Ind J Exp Biol 42:224–226

    CAS  Google Scholar 

  • Suchalatha S, Srinivasan P, Shyamala Devi CS (2007) Effect of T. chebula on mitochondrial alterations in experimental myocardial injury. Chem Biol Interact 169:145–153

    Article  PubMed  CAS  Google Scholar 

  • Sushama Kumari S, Jayadeep A, Kumar JS, Menon VP (1989) Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol. Ind J Exp Biol 27:134–137

    CAS  Google Scholar 

  • Takasawa M, Hayakawa M, Sugiyama S, Hattori K, Ito T, Ozawa T (1993) Age-associated damage in mitochondrial function in rat hearts. Exp Gerontol 28:269–280

    Article  PubMed  CAS  Google Scholar 

  • Tappel AL (1973) Lipid peroxidation damage to cell components. Fed Proc 32:1870–1874

    PubMed  CAS  Google Scholar 

  • Wexler BC, Greenberg BP (1978) Protective effects of clofibrate on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats. Atherosclerosis 29:373–375

    Article  PubMed  CAS  Google Scholar 

  • Wickens AP (2001) Ageing and the free radical theory. Respir Physiol 128:379–391

    Article  PubMed  CAS  Google Scholar 

  • Williams JR, Coorkey BE (1967) Assay of intermediates of the citric acid cycle and related compounds by flourimetric enzymatic methods. In: Lowenstein JM (ed) Methods in enzymology. Academic, New York, pp 488–492

    Google Scholar 

  • Xia T, Jiang C, Li L, Wu C, Chen Q, Liu SS (2002) A study on permeability transition pore opening and cytochrome-c-release from mitochondria, induced by caspase-3 in vitro. FEBS Lett 510:62–66

    Article  PubMed  CAS  Google Scholar 

  • Zarco P, Henar Zarco MH (1996) Biochemical aspects of cardioprotection. Medicographia 18:18–21

    Google Scholar 

  • Zilversmit DB, Davis AK (1950) Microdetermination of plasma phospholipids by trichloro aectic acid precipitation. J Lab Clin Med 35:155–160

    PubMed  CAS  Google Scholar 

  • Zlatkis A, Zak B, Boyle AJ (1953) A new method for the direct determination of serum cholesterol. J Lab Clin Med 41:486–492

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biotechnology, Annamalai University, Annamalai nagar, 608002, Tamil Nadu, India

    Kandaswamy Senthil Kumaran & Ponnian Stanely Mainzen Prince

Authors
  1. Kandaswamy Senthil Kumaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ponnian Stanely Mainzen Prince
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ponnian Stanely Mainzen Prince.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumaran, K.S., Prince, P.S.M. Caffeic acid protects rat heart mitochondria against isoproterenol-induced oxidative damage. Cell Stress and Chaperones 15, 791–806 (2010). https://doi.org/10.1007/s12192-010-0187-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-010-0187-9

Keywords

Search

Navigation