Suppression of oxidative stress as a mechanism of reduction of hypercholesterolemic atherosclerosis by aspirin.

Abstract

Hypercholesterolemia increases the formation of arachidonic acid and thereby synthesis of prostaglandins and leukotrienes. During synthesis of these eicosanoids, oxyradicals are produced. Oxyradicals have been implicated in the development of hypercholes-terolemic atherosclerosis. Aspirin, an inhibitor of synthesis of prostaglandins, would prevent the generation of oxyradicals and hence would prevent the development of atherosclerosis. The purpose of the investigation was to determine if aspirin attenuates the development of hypercholesterolemic atherosclerosis, and if this attenuation is associated with a decrease in the oxidative stress. Three groups of rabbits were used for this study: Group I, control; Group II, 0.5% cholesterol; Group III, 0.5% cholesterol plus 0.068% aspirin. Blood samples were collected before and after 1 and 2 months of experimental diets for measurement of serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum malondialdehyde, and white blood cell chemiluminescence, a measure of oxyradicals produced by white blood cells. Aortas were removed at the end of the protocol for the measurement of atherosclerotic plaques, malondialdehyde and aortic chemiluminescence, a measure of antioxidant reserve. Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and ratio of total cholesterol to high-density lipoprotein cholesterol increased to a similar extent in Groups II and III compared to Group I. Serum triglycerides increased in both Groups II and III; however, the increase was greater in Group III than in Group II. Levels of serum and aortic malondialdehyde, and white blood cell-chemiluminescence were higher in Group II compared to Group I. Aspirin decreased the levels of these parameters. Antioxidant reserve increased in both Groups II and III, the increase being greater in the latter than the former. White blood cell-chemiluminescence increased in Group II compared to Group I, but remained unaltered in Group III compared to Group I. Aspirin treatment reduced the development of atherosclerosis by approximately 47%. These results suggest that aspirin, an inhibitor of cyclooxygenase, reduced the development of hypercholesterolemic atherosclerosis, and this effect was associated with a decrease in the oxidative stress.