Skip to main content
Log in

Protective Effects of Rutin on Mitochondrial Damage in Isoproterenol-Induced Cardiotoxic Rats: An In Vivo and In Vitro Study

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Consumption of diets rich in flavonoids is associated with reduced risk of cardiovascular diseases such as myocardial infarction. Cardiotoxicity was induced in rats by subcutaneous injection of isoproterenol at an interval of 24 h for 2 days. Isoproterenol-induced rats showed a significant increase in the levels of heart mitochondrial lipids, lipid peroxidation products, calcium and a significant decrease in the activities/levels of mitochondrial antioxidants, enzymes and adenosine triphosphate. Isoproterenol-induced rats also showed an increase in the intensities of serum lactate dehydrogenase-1 and 2 isoenzyme bands. Pretreatment with rutin at the dose of 80 mg/kg daily for 42 days to isoproterenol-induced rats prevented all the biochemical alterations. Transmission electron microscopic study also confirmed the protective effects of rutin on the structure of heart mitochondria. Thus, rutin reduced the extent of mitochondrial damage induced by isoproterenol and prevented cardiac mitochondrial dysfunction. The possible mechanisms for the observed effects of rutin could be due to scavenging free radicals, lowering lipid peroxides, lipids and calcium, improving multienzyme activities, glutathione levels, adenosine triphosphate levels, thereby improving cardiac mitochondrial structure and function. 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

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

Similar content being viewed by others

References

  1. Mohanty, I., Arya, D. S., Dinda, A., Talwar, K. K., Joshi, S., & Gupta, S. K. (2004). Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction. Basic and Clinical Pharmacology and Toxicology, 94, 184–190.

    CAS  PubMed  Google Scholar 

  2. Sushama Kumari, S., Jayadeep, A., Kumar, J. S., & Menon, V. P. (1989). Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol. Indian Journal of Experimental Biology, 27, 134–137.

    CAS  Google Scholar 

  3. Chein, K. R., Abrams, J., Serroni, A., Martin, J. T., & Farber, J. L. (1978). Accelerated phospholipid degradation and associated membrane dysfunction in irreversible, ischemic liver cell injury. Journal of Biological Chemistry, 253, 4809–4817.

    Google Scholar 

  4. Geng, B., Chang, L., Pan, C., Qi, Y., Zhao, J., Pang, Y., et al. (2004). Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochemical and Biophysical Research Communications, 318, 756–763.

    Article  CAS  PubMed  Google Scholar 

  5. Banerjee, S. K., & Maulik, S. K. (2002). Effect of garlic on cardiovascular disorders: A review. Nutrition Journal, 1, 4.

    Article  PubMed  Google Scholar 

  6. Hertog, M. G., Hollman, P. C., Katan, M. B., & Kromhout, D. (1993). Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutrition and Cancer, 20, 21–29.

    Article  CAS  PubMed  Google Scholar 

  7. Janbaz, K. H., Saeed, S. A., & Gilani, A. H. (2002). Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents. Fitoterapia, 73, 557–563.

    Article  CAS  PubMed  Google Scholar 

  8. Stanely Mainzen Prince, P., & Karthick, M. (2007). Preventive effect of rutin on lipids, lipoproteins and ATPases in isoproterenol-induced myocardial infarction in rats. Journal of Biochemical and Molecular Toxicology, 21, 1–6.

    Article  CAS  PubMed  Google Scholar 

  9. Karthick, M., & Stanely Mainzen Prince, P. (2006). Preventive effect of rutin, a bioflavonoid, on lipid peroxides and antioxidants in isoproterenol-induced myocardial infarction in rats. Journal of Pharmacy and Pharmacology, 58, 701–707.

    Article  CAS  PubMed  Google Scholar 

  10. Takasawa, M., Hayakawa, M., Sugiyama, S., Hattori, K., Ito, T., & Ozawa, T. (1993). Age-associated damage in mitochondrial function in rat hearts. Experimental Gerontology, 28, 269–280.

    Article  CAS  PubMed  Google Scholar 

  11. Zlatkis, A., Zak, B., & Boyle, A. J. (1953). A new method for the direct determination of serum cholesterol. Journal of Laboratory and Clinical Medicine, 41, 486–492.

    CAS  PubMed  Google Scholar 

  12. Fossati, P., & Prencipe, L. (1982). Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clinical Chemistry, 28, 2077–2080.

    CAS  PubMed  Google Scholar 

  13. Falholt, K., Lund, B., & Falholt, W. (1973). An easy colorimetric micromethod for routine determination of free fatty acids in plasma. Clinica Chimica Acta, 46, 105–111.

    Article  CAS  Google Scholar 

  14. Fraga, C. G., Leibovitz, B. E., & Tappel, 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.

    Article  CAS  PubMed  Google Scholar 

  15. Kakkar, P., Das, B., & Viswanathan, P. N. (1984). A modified spectrophotometric assay of superoxide dismutase. Indian Journal of Biochemistry and Biophysics, 21, 130–132.

    CAS  Google Scholar 

  16. Sinha, A. K. (1972). Colorimetric assay of catalase. Analytical Biochemistry, 47, 389–394.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. Ellman, G. L. (1959). Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 82, 70–77.

    Article  CAS  PubMed  Google Scholar 

  19. King, J. (1965). Isocitrate dehydrogenase. In J. C. King & D. Van (Eds.), Practical clinical enzymology (p. 363). London: Nostrand.

    Google Scholar 

  20. Slater, E. C., & Borner, W. D. (1952). The effect of fluoride on the succinic oxidase system. Biochemical Journal, 52, 185–196.

    CAS  PubMed  Google Scholar 

  21. Mehler, A. H., Kornberg, A., Crisolia, S., & Ochoa, S. (1948). The enzymatic mechanism of oxidation-reductions between malate or isocitrate and pyruvate. Journal of Biological Chemistry, 174, 961–977.

    CAS  PubMed  Google Scholar 

  22. Reed, L. J., & Mukherjee, R. B. (1969). α-Ketoglutarate dehydrogenase complex from Escherichia coli. In J. M. Lowenstein (Ed.), Methods in enzymology (pp. 53–61). London: Academic Press.

    Google Scholar 

  23. Minakami, S., Ringler, R. L., & Singer, T. P. (1962). Studies on the respiratory chain-linked dihydrodiphosphopyridine nucleotide dehydrogenase. I. Assay of the enzyme in particulate and in soluble preparations. Journal of Biological Chemistry, 237, 569–576.

    CAS  PubMed  Google Scholar 

  24. Pearl, W., Cascarano, J., & Zweifach, B. W. (1963). Microdetermination of cytochrome oxidase in rat tissues by oxidation of N-phenlyl-p-phenylene diamine or ascorbic acid. Journal of Histochemistry and Cytochemistry, 11, 102–107.

    CAS  Google Scholar 

  25. Williams, J. R., & Coorkey, B. E. (1967). Assay of intermediates of the citric acid cycle and related compounds by flourimetric enzymatic methods. In J. M. Lowenstein (Ed.), Methods in enzymology (pp. 488–492). New York: Academic Press.

    Google Scholar 

  26. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with Folin’s phenol reagent. Journal of Biological Chemistry, 193, 265–275.

    CAS  PubMed  Google Scholar 

  27. McKenzie, D., & Henderson, A. R. (1983). Electrophoresis of lactate dehydrogenase isoenzymes. Clinical Chemistry, 29, 189–195.

    CAS  PubMed  Google Scholar 

  28. Nishikimi, M., Appaji, N., & Yagi, K. (1972). The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochemical and Biophysical Research Communications, 46, 849–854.

    Article  CAS  PubMed  Google Scholar 

  29. Halliwell, B., Gutteridge, J. M., & Aruoma, O. I. (1987). The deoxyribose method: A simple “test-tube” assay for determination of rate constants for reactions of hydroxyl radicals. Analytical Biochemistry, 165, 215–219.

    Article  CAS  PubMed  Google Scholar 

  30. Belchenko, D. I., Sopka, N. V., Kalinkin, M. N., Khanina, N. I. A., & Chelnokov, V. S. (1990). The metabolic changes in myocardial subcellular fractions in the pathogenesis of ischemic heart disease. Patologicheskaia Fiziologiia i Eksperimentalnaia Terapiia, 2, 16–20.

    Google Scholar 

  31. Vijayapadma, V., & Shyamaladevi, C. S. (2001). Effect of fish oil on mitochondrial respiration in isoproterenol induced myocardial infarction in rats. Indian Journal of Experimental Biology, 40, 268–272.

    Google Scholar 

  32. Yogeeta, S. K., Raghavendran, H. R., Gnanapragasam, A., Subhashini, R., & Devaki, T. (2006). Ferulic acid with ascorbic acid synergistically extenuates the mitochondrial dysfunction during beta-adrenergic catecholamine induced cardiotoxicity in rats. Chemico-Biological Interactions, 163, 160–169.

    Article  CAS  PubMed  Google Scholar 

  33. Pietta, P. G. (2000). Flavonoids as antioxidants. Journal of Natural Products, 63, 1035–1042.

    Article  CAS  PubMed  Google Scholar 

  34. Spencer, J. P., Jenner, A., Aruoma, O. I., Evans, P. J., Kaur, H., Dexter, D. T., et al. (1994). Intense oxidative DNA damage promoted by L-dopa and its metabolites. Implications for neurodegenerative disease. FEBS Letters, 353, 246–250.

    Article  CAS  PubMed  Google Scholar 

  35. Bokkenheuser, V. D., Shackleton, C. H., & Winter, J. (1987). Hydrolysis of dietary flavoniod glycosides by strains of intestinal Bacteroides from humans. Biochemical Journal, 248, 953–956.

    CAS  PubMed  Google Scholar 

  36. Ueno, I., Nakano, N., & Hirono, I. (1983). Metabolic fate of [14C] quercetin in the ACI rats. Japanese Journal of Experimental Medicine, 53, 41–50.

    CAS  PubMed  Google Scholar 

  37. Hollman, P. C. H., & Katan, M. B. (1996). Absorption, metabolism and bioavailability of flavonoids. In C. Rice-Evans, L. Packer (eds.), Flavonoids in health and diseases (pp. 483–522) New York.

  38. Boyle, S. P., Dobson, V. L., Duthie, S. J., Hinselwood, D. C., Kyle, J. A., & Collins, A. R. (2000). Bioavailability and efficiency of rutin as an antioxidant: A human supplementation study. European Journal of Clinical Nutrition, 54, 774–782.

    Article  CAS  PubMed  Google Scholar 

  39. Erlund, I., Kosonen, T., Alfthan, G., Maenpaa, J., Perttunen, K., Kenraali, J., et al. (2000). Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. European Journal of Clinical Pharmacology, 56, 545–553.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P. Stanely Mainzen Prince.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Punithavathi, V.R., Shanmugapriya, K. & Stanely Mainzen Prince, P. Protective Effects of Rutin on Mitochondrial Damage in Isoproterenol-Induced Cardiotoxic Rats: An In Vivo and In Vitro Study. Cardiovasc Toxicol 10, 181–189 (2010). https://doi.org/10.1007/s12012-010-9077-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-010-9077-8

Keywords

Navigation