Abstract

Objective: The objective of the present study is to investigate whether rosmarinic acid (RA) could prevent cardiac fibrosis induced in a rat model of insulin resistance. Methods: Insulin resistance was induced in rats by feeding a semi-synthetic diet containing fructose (60%) as the source of carbohydrate for 60 days. Control group received a diet containing starch in place of fructose. RA (10mg/kg) administration was initiated from the 16th day of the experimental period. Electrocardiography, fibrotic changes and reactive oxygen species (ROS) production were measured at the end of 60 days.Results: Fructose-fed rats (FFR) showed insulin resistance and significant changes in the electrocardiogram pattern and heart rate. Increased cardiac superoxide production (50%) accompanied by collagen deposition and increased expression of transforming growth factor (TGF)-毬 1, 毩 -smooth muscle actin (毩 -SMA) and matrix metalloproteinase (MMPs)-2 and -9 and decreased expression of tissue inhibitors of MMP (TIMPs)-1 and -2 were noted in the FFR. This was accompanied by increased angiotensin II (AII) in plasma and angiotensin II type 1 receptor (AT1R) and fibronectin mRNA in heart. RA treatment restored the electrocardiographic patterns and regulated heart rate. The levels of superoxide, AII and collagen and the expression of TGF-毬 1, 毩 -SMA, MMPs and AT1R were significantly reduced while the expression of TIMPs was increased upon RA treatment. Masson’s trichrome stained heart sections revealed reduction in collagen in RA-supplemented FFR. Conclusions: We conclude that RA treatment improves cardiac function and prevents myocardial fibrotic changes and hence could be useful as a cardioprotective agent under insulin resistant conditions

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