title: Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.
abstract: Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.
authors.affiliation: Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa, 125 055, Haryana, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Garg
authors.affiliation: Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa, 125 055, Haryana, India. 7drdeepa@gmail.com.
authors.forename: Deepa
authors.initials: D
authors.lastname: Khanna
authors.affiliation: Cardiovascular Pharmacology Division, Department of Pharmacology, Rajendra Institute of Technology and Sciences, Sirsa, 125 055, Haryana, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kalra
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100, Bedong, Kedah DarulAman, Malaysia.
authors.forename: Pitchai
authors.initials: P
authors.lastname: Balakumar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*
chemical_list: D002316:Cardiotonic Agents; D000068718:Rosuvastatin Calcium; D007545:Isoproterenol; D011345:Fenofibrate
keywords: fenofibrate; inflammation; isoproterenol; low-dose strategy; myocardial infarction; oxidative stress; rosuvastatin