Open AccessRosmarinic acid treatment alleviates fibrotic changes in the myocardium induced in a rat model of insulin resistance
Author(s) -
Dhanapalan Karthik,
Elumalai Arunkumar,
P. N. Viswanathan,
Carani Venkatraman Anuradha
Publication year - 2012
Publication title -
asian pacific journal of tropical disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.208
H-Index - 33
ISSN - 2222-1808
DOI - 10.1016/s2222-1808(12)60292-8
Subject(s) - medicine , endocrinology , insulin resistance , angiotensin ii , fibrosis , myocardial fibrosis , fibronectin , cardiac fibrosis , insulin , superoxide , cardiac function curve , chemistry , receptor , heart failure , extracellular matrix , biochemistry , enzyme
Objective: The objective of the present study is to investigate whether rosmarinic acid (RA)\udcould prevent cardiac fibrosis induced in a rat model of insulin resistance. Methods: Insulin\udresistance was induced in rats by feeding a semi-synthetic diet containing fructose (60%) as\udthe source of carbohydrate for 60 days. Control group received a diet containing starch in place\udof fructose. RA (10mg/kg) administration was initiated from the 16th day of the experimental\udperiod. Electrocardiography, fibrotic changes and reactive oxygen species (ROS) production were\udmeasured at the end of 60 days.Results: Fructose-fed rats (FFR) showed insulin resistance and\udsignificant changes in the electrocardiogram pattern and heart rate. Increased cardiac superoxide\udproduction (50%) accompanied by collagen deposition and increased expression of transforming\udgrowth factor (TGF)-毬 1, 毩 -smooth muscle actin (毩 -SMA) and matrix metalloproteinase (MMPs)-2\udand -9 and decreased expression of tissue inhibitors of MMP (TIMPs)-1 and -2 were noted in the\udFFR. This was accompanied by increased angiotensin II (AII) in plasma and angiotensin II type 1\udreceptor (AT1R) and fibronectin mRNA in heart. RA treatment restored the electrocardiographic\udpatterns and regulated heart rate. The levels of superoxide, AII and collagen and the expression\udof TGF-毬 1, 毩 -SMA, MMPs and AT1R were significantly reduced while the expression of TIMPs\udwas increased upon RA treatment. Masson’s trichrome stained heart sections revealed reduction\udin collagen in RA-supplemented FFR. Conclusions: We conclude that RA treatment improves\udcardiac function and prevents myocardial fibrotic changes and hence could be useful as a\udcardioprotective agent under insulin resistant conditions