Antiatherosclerotic effect of probucol in WHHL rabbits: are there plasma parameters to evaluate this effect?

Abstract

Probucol has been used as a lipid-lowering agent for over 10 years. Lately it has been found that its antiatherogenic action is due mainly to its antioxidative capacity, in addition to its known lipid-lowering effect. To study the antioxidative capability of probucol and its influence on plaque development we used the animal model of the LDL-receptor-defective Watanabe heritable hyperlipidemic (WHHL) rabbit. In this study we measured all lipid values before and after probucol feeding and compared them with corresponding values in untreated controls. Probucol levels were determined, as were the physiological antioxidants alpha and gamma tocopherol (vitamin E). Thiobarbituric reactive substances were measured in plasma as a parameter for lipid peroxidation. In addition to the biochemical measurements the plaque area was analyzed macroscopically and microscopically to check the antiatherosclerotic effect and correlate it with the biochemical parameters. In four experiments we showed that probucol treatment in WHHL rabbits decreases the progression of atherosclerotic plaques by way of a combined lipid-lowering and antioxidative effect.