Anti-inflammatory drugs in experimental atherosclerosis. Part 6. Combination therapy with steroid and non-steroid agents.
The pathological changes which accompany enhanced cholesterol deposition in atherosclerosis include inflammatory responses mediated by the prostaglandin cyclooxygenase and lipoxygenase-leukotriene metabolite of the arachidonic acid cascade. Cortisone suppresses arachidonic acid release, whereas non-steroid anti-inflammatory drugs inhibit principally the cyclooxygenase enzyme. Groups of New Zealand white rabbits were fed a 1% cholesterol diet for 12 weeks. Diets of selected groups were further supplemented daily with the non-steroid anti-inflammatory drugs phenylbutazone (100 mg), oxyphenylbutazone (240 mg), flufenamic acid (100 mg), either singly or in combination with cortisone acetate (10 mg or 5 mg), or 9-alpha-fluorohydrocortisone (30 micrograms or 200 micrograms). Serum lipid levels were measured at 0, 4, 8 and 12 weeks, and atherosclerotic plaque intensity in thoracic aorta was measured at 12 weeks using a planimetric technique: serum cholesterol levels in control groups increased from 38 +/- 5 to 1190 +/- 139 mg/100 ml. Neither the rate of increase nor the final lipid values attained were significantly changed by the non-steroid drugs. The non-steroid drugs reduced plaque coverage by about one third (phenylbutazone 34 +/- 10%, flufenamic acid 36 +/- 11%) compared to controls. In combination therapy, addition of cortisone acetate resulted in further plaque suppression. Cortisone 10 mg + phenylbutazone gave 100% suppression; cortisone 5 mg + phenylbutazone gave 82 +/- 18%, and cortisone 5 mg + flufenamic acid gave 84 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000009:adverse effects; D003348:Cortisone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005438:Fludrocortisone / Q000627:therapeutic use*; D005439:Flufenamic Acid / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D010113:Oxyphenbutazone / Q000627:therapeutic use; D010653:Phenylbutazone / Q000627:therapeutic use*; D011817:Rabbits
D002791:Cholesterol, Dietary; D008055:Lipids; D005439:Flufenamic Acid; D002784:Cholesterol; D010653:Phenylbutazone; D010113:Oxyphenbutazone; D005438:Fludrocortisone; D003348:Cortisone