The hypolipidemic
fibrates have been identified as agonists of the
peroxisome proliferator-activated receptor alpha (
PPARalpha), which plays a critical role in the regulation of cardiac
fatty acid metabolism. Despite the widespread clinical use of
fibrates, their role in myocardial oxidative stress and
fatty acid composition is less known. In this study, male Sprague-Dawley rats were treated with either vehicle (
olive oil, 1 ml/kg) or
clofibrate (300 mg/kgday i.p.) for 1-14 days. Lipid peroxidation in heart homogenate was determined by
thiobarbituric acid reactive substance (
TBARS) assay. Results show that hearts from
clofibrate-treated rats are more susceptible to FeSO(4)-induced
TBARS production. The
antioxidants including
catalase and
glutathione-related
enzymes were marginally affected. We demonstrated that myocardial
fatty acid composition was dramatically altered by
clofibrate treatment. In hearts from
clofibrate-treated rats, the principal n-6
polyunsaturated fatty acids (PUFAs),
linoleic acid (C18:2 n-6) and
arachidonic acid (C20:4 n-6), was significantly reduced, while the content of the principal
n-3 PUFA,
docosahexaenoic acid (C22:6 n-3), was markedly increased. The overall effect was to reduce n-6/n-3 ratio and increase the unsaturation extent of myocardial
fatty acids. Functional study showed that hearts from
clofibrate-treated rats had an improved recovery of post-ischemic contractile function and reduced
ischemia/reperfusion (I/R)-induced
infarct size. The data shows that
clofibrate has a profound impact on cardiac
fatty acid composition, which may contribute to its cardioprotective effect.