Antioxidant Probucol Attenuates Myocardial Oxidative Stress and Collagen Expressions in Post-Myocardial Infarction Rats

Abstract

This study was designed to evaluate the effects of the antioxidant probucol on myocardial oxidative stress and collagen remodeling by determining type I and III collagen together with relevant collagen mRNA expressions in both the infarcted and noninfarcted myocardium in post-myocardial infarction (MI) rats. Acute myocardial infarction was induced by ligation of the left anterior coronary artery in rats. Rats surviving 24 h after MI were randomly assigned to the group treated with vehicle or probucol. Sham-operated rats served as controls. Cardiac hemodynamics, parameters of oxidative stress in noninfarcted myocardium, collagen content, collagen volume density fraction, collagen type I and III together with the ratio, type I and III collagen mRNA were evaluated after 6 weeks. Probucol decreased oxidative stress as assessed by increased myocardial total antioxidative capacity, superoxide dismutase (SOD) activity, and SOD-to-myocardial malondialdehyde (MDA) ratio accompanied by decreased MDA level, decreased left ventricular end diastolic pressure and LV -dP/dtmax, and decreased collagen content and CVF in the noninfarcted area accompanied by decrease of type I and III mRNA expressions. The increase of collagen type I/III ratio in noninfarcted area was suppressed by probucol accompanied by inhibition of the increase in type I/III collagen mRNA ratio. Probucol did not affect collagen type I/III ratio and the corresponding mRNA ratio in the infarcted area. These results suggest that suppression of oxidative stress by probucol may attenuate collagen synthesis by inhibition of collagen mRNA expressions and improve diastolic function.