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.
- Antiatherosclerotic effect
- In vivo model
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine