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Molecular and Cellular Biochemistry

, Volume 394, Issue 1–2, pp 163–176 | Cite as

Carnosic acid promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress and apoptosis in mice

  • Bidya Dhar Sahu
  • Uday Kumar Putcha
  • Madhusudana Kuncha
  • Shyam Sunder Rachamalla
  • Ramakrishna SistlaEmail author
Article

Abstract

Carnosic acid is a well-known antioxidant. Recently, it has been identified as modulator of nuclear factor erythroid 2-related factor 2 (Nrf2). The effect of carnosic acid in the context of cardiovascular disorders has not been studied. In the present study, we investigated the beneficial effect and the underlying cardioprotective mechanism of carnosic acid by using mouse model of isoproterenol (ISO)-induced myocardial stress. Elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and myofibrillar degeneration with necrotic damage, and the presence of epicardial inflammatory infiltrate (H & E staining) confirmed the ISO-induced myocardial stress. Myocardial content of vitamin C, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, NAD(P)H: quinine oxidoreductase 1, superoxide dismutase, catalase, nuclear translocation of Nrf2 and protein expression heme oxygenase-1 were evaluated. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myocardial expression of cleaved caspase-3, caspase-9, p53, Bax, and Bcl-2 were investigated to assess the apoptotic cell death. Pretreatment with carnosic acid attenuated ISO-induced elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and histopathological alterations in heart. Moreover, carnosic acid enhanced the nuclear translocation of Nrf2 and up-regulated the phase II/antioxidant enzyme activities. Furthermore, TUNEL assay and apoptosis-related protein analysis indicated that carnosic acid prevented ISO-induced cardiomyocyte apoptosis. Isoproterenol-induced myocardial lipid peroxidation and protein oxidation were also significantly decreased by carnosic acid pretreatment. The overall results clearly indicate that therapeutic application of carnosic acid might be beneficial in treating cardiovascular disorders.

Keywords

Carnosic acid Isoproterenol Nuclear translocation of Nrf2 Oxidative stress Apoptosis 

Notes

Acknowledgments

The present study was partially supported by a research grant from CSIR project ‘SMiLE’ (CSC 0111). We thank the Director, CSIR-IICT, Hyderabad, India for constant support, encouragement and for providing necessary facilities. B. D. S thanks Council of Scientific and Industrial Research (CSIR), New Delhi for providing Senior Research Fellowship (SRF).

Conflict of interest

There is no conflict of interest to disclose.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Bidya Dhar Sahu
    • 1
  • Uday Kumar Putcha
    • 2
  • Madhusudana Kuncha
    • 1
  • Shyam Sunder Rachamalla
    • 3
  • Ramakrishna Sistla
    • 1
    Email author
  1. 1.Medicinal Chemistry & Pharmacology DivisionCSIR-Indian Institute of Chemical Technology (IICT)HyderabadIndia
  2. 2.Division of PathologyNational Institute of NutritionHyderabadIndia
  3. 3.Faculty of PharmacyOsmania UniversityHyderabadIndia

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