Curcumin protects rat myocardium against isoproterenol-induced ischemic injury: attenuation of ventricular dysfunction through increased expression of Hsp27 along with strengthening antioxidant defense system.
This investigation examines the role of heat shock protein (Hsp) 27 and its modulation by curcumin in isoproterenol-induced myocardial ischemic injury in rats. Evidence from hemodynamic functions and oxidative stress parameters were also included in the study. The animals were divided into control, isoproterenol, and curcumin 100, 200, and 400 mg/kg treatment groups. Curcumin was administered orally for 15 days to all the treated groups. On 13th and 14th day, isoproterenol (85 mg/kg, s.c.) was injected to curcumin-treated and isoproterenol group. On day 15, hemodynamic parameters were recorded. Thereafter, animals were sacrificed and hearts were kept for biochemical and Western blot analysis. We found dose-dependent increase in the expression of Hsp27 with drastic fall at highest dose. Hemodynamically, the lower 2 doses also restored the cardiac function as evident by improved contractile functions, decreased left ventricular end-diastolic pressure, restored arterial pressures, and heart rate. In addition, there was an increase in then level of superoxide dismutase, catalase, reduced glutathione, and decreased production of thiobarbituric acid reactive substances and leakage of cardiac necroenzyme creatine kinase-MB isoenzyme and lactate dehydrogenase in curcumin 100 and 200 mg/kg group as compared with isoproterenol. However, at a dose of 400 mg/kg, there was ineffectual protection against isoproterenol-induced myocardial damage. Our results suggested 200 mg/mg as the most optimum therapeutic dose showing improved cardiac function due to stabilization of cytoskeleton structure which in turn is attributed to Hsp27 expression along with fortified antioxidant defense system.
Tanwar
Vineeta
V
Cardiovascular Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Sachdeva
Jaspreet
J
Golechha
Mahaveer
M
Kumari
Santosh
S
Arya
Dharamvir Singh
DS
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000517:prevention & control*
D000975:Antioxidants; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D052279:Creatine Kinase, MB Form; D005978:Glutathione; D003474:Curcumin; D007545:Isoproterenol