Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits.
The effects of clodronate, a bisphosphonate for the treatment of hypercalcemia, on the progress of atherosclerosis were studied in rabbits fed with a high-cholesterol (1%) diet and treated simultaneously with disodium clodronate 0 (saline), 1, 5, or 25 mg/kg intravenously twice a week for 6, 9, and 12 weeks. In 9 to 12 weeks, plasma total cholesterol increased from 0.8 +/- 0.3 mmol/L (mean +/- SD) in rabbits fed the standard diet to 46 +/- 17 mmol/L in animals subjected to high-cholesterol diet. Clodronate did not influence the cholesterol concentration in plasma. None of the parameters studied were changed by clodronate within 6 weeks after beginning the treatment. In 9 to 12 weeks (n = 7 to 9), plasma total Ca++ concentration was decreased from 3.55 +/- 0.12 mmol/L in the saline group to 3.36 +/- 0.16 mmol/L in the group on the greatest clodronate dose (p < 0.05). Free and esterified cholesterol and total Ca++ concentrations in the wall of thoracic aorta were reduced by the greatest dose of clodronate, compared with the groups treated with saline solution or smaller doses of the drug (p < 0.05). At 12 weeks, the greatest dose of clodronate also reduced the visible and lipid-stained atheromatous areas in the thoracic and abdominal aorta, compared with those in the saline and the other clodronate dose groups (p < 0.05). The results suggest that a high dose of clodronate inhibits the development of diet-induced atherosclerosis in rabbits.
Ylitalo
R
R
Department of Clinical Medicine, University of Tampere, Finland.
Oksala
O
O
Ylä-Herttuala
S
S
Ylitalo
P
P
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004002:Clodronic Acid / Q000494:pharmacology*; D004041:Dietary Fats; D004305:Dose-Response Relationship, Drug; D004573:Electrolytes / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D011817:Rabbits; D013997:Time Factors
D004041:Dietary Fats; D004573:Electrolytes; D004002:Clodronic Acid; D002784:Cholesterol