title: Kampeferol protects against oxidative stress and apoptotic damage in experimental model of isoproterenol-induced cardiac toxicity in rats.
abstract: BACKGROUND
  Myocardial infarction (MI) continues to be associated with high morbidity and mortality worldwide despite the availability of current therapeutic modalities. Kaempferol (KMP), a dietary flavonoid, possesses good antioxidant, immunomodulatory and anti-apoptotic properties and has been evaluated in the present study for its role in mitigating myocardial injury following MI.
  
  
  OBJECTIVE
  In this study, the ability of KMP to protect heart against isoproterenol (ISO) induced oxidative stress and myocardial infarction was evaluated.
  
  
  METHODS
  Male Wistar rats (n=48) were administered KMP (5, 10 & 20mg/kg/day, i.p.) or vehicle for 15 days with ISO, 85mg/kg, subcutaneously, for 2 consecutive days was also administered at 24h interval on the 13th and 14th days. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Later on blood sample was collected and heart was removed to estimate biochemical, histopathological, ultrastructural and immuohistochemical studies respectively.
  
  
  RESULTS
  ISO-treated rats showed a significant reduction in arterial pressure, maximum rate of development of left ventricular pressure and increase in left ventricular end-diastolic pressure. Also, there was a significant decrease in antioxidant enzyme levels such as superoxide dismutase, catalase and glutathione and increase in the level of malondialdehyde and serum TNF-α and IL-6 levels. In addition, the cardiac injury markers such as creatine kinase-MB and lactate dehydrogenase were increased in the serum. Furthermore, immunohistochemistry revealed an increased Bax/Bcl-2 ratio in the myocardium. KMP (5, 10 and 20mg/kg) dose dependently restored hemodynamic, left ventricular functions, decreased cardiac injury marker enzymes in serum, increased antioxidant levels, reduced lipid peroxidation and TNF-α level and apoptosis. Histopathological and ultrastructural studies support the protective effect of KMP in ISO-induced myocardial infarcted rats.
  
  
  CONCLUSIONS
  Thus, the present study revealed that KMP mitigates myocardial damage in ISO-induced cardiac injury by maintaining hemodynamic and biochemical parameters and reducing inflammation owing to its anti-apoptotic, anti-inflammatory and antioxidant activities. It may be concluded that a diet containing KMP may be beneficial in those who are at the risk of myocardial injury.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Suchal
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Salma
authors.initials: S
authors.lastname: Malik
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Nanda
authors.initials: N
authors.lastname: Gamad
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Rajiv Kumar
authors.initials: RK
authors.lastname: Malhotra
authors.affiliation: Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra-425405, India.
authors.forename: Sameer N
authors.initials: SN
authors.lastname: Goyal
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Jagriti
authors.initials: J
authors.lastname: Bhatia
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India. Electronic address: dsarya16@gmail.com.
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D066126:Cardiotoxicity / Q000188:drug therapy; D002374:Catalase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D015850:Interleukin-6 / Q000378:metabolism; D007545:Isoproterenol / Q000633:toxicity; D044949:Kaempferols / Q000494:pharmacology* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008962:Models, Theoretical; D009203:Myocardial Infarction / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D015850:Interleukin-6; D044949:Kaempferols; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C006552:kaempferol; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D007545:Isoproterenol
keywords: Apoptosis; Cardiotoxicity; Inflammation; Isoproterenol; Kaempferol; Oxidative stress