Dual effects of the antioxidant agents probucol and carvedilol on proliferative and fatty lesions in hypercholesterolemic rabbits Original Research Article

The in vivo direct antiatherogenic activity of the antioxidant probucol (200 mg/kg per day) or the β-blocker with antioxidant properties carvedilol (10 and 20 mg/kg per day) was tested in the same animal in two different types of atherosclerotic lesion (proliferative and fatty lesions) induced in cholesterol-fed rabbits (1%). Drugs were given daily mixed with standard diet for 8 weeks; body weight and plasma lipid profile were not different among groups throughout the study. Aortic fatty lesions were induced by cholesterol feeding (n=25 in each group) and their extent expressed as % of aorta inner surface covered by plaques was significantly reduced by both drugs (28.2±9.6%, P<0.05, 19.9±6.2%, P<0.01 for low- and high-dose carvedilol, respectively; 22.3±7.6%, P<0.01 for probucol, versus 41.6±10.7% in control rabbits). Proliferative lesions were obtained by positioning a hollow silastic collar around one carotid artery 6 weeks after dietary and drug treatments started (n=5 in each group). The neointimal formation, mostly composed by myocytes, was determined by measuring cross-sectional thickness ratio of intimal (I) and medial (M) tissue of fixed arteries. In untreated animals, collared arteries resulted in a significant neointimal cell accumulation compared to the sham (1.10±0.14 versus 0.02±0.01) without change in medial thickness. I/M ratio was reduced by about 50% in animals treated with probucol (0.51±0.1) and carvedilol (0.66±0.21 and 0.52±0.1 in the low- and high-dose group, respectively). Total plasma TBARS were more than 50% lower in both probucol- and high-dose carvedilol-treated rabbits. Results show that pharmacological pretreatment with antioxidants directly inhibits early atherogenic processes, representing a potentially useful approach in the prevention of atherosclerosis.