title: Carnosic acid promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress and apoptosis in mice.
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,
  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.
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad, 500 007, India.
authors.forename: Bidya Dhar
authors.initials: BD
authors.lastname: Sahu
authors.forename: Uday Kumar
authors.initials: UK
authors.lastname: Putcha
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Kuncha
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Rachamalla
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007545:Isoproterenol; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D045784:Abietanes; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010936:Plant Extracts; D007545:Isoproterenol; C018381:salvin