Evaluation of timefurone, a new anti-atherosclerotic drug, for its effects on lipoprotein cholesterol in male cynomolgus monkeys fed an atherogenic diet for 18 months.
Forty male cynomolgus monkeys were fed a nutritionally complete diet containing butter and 0.5% cholesterol for 18 months to ensure development of atherosclerosis. Timefurone was administered daily at 10 mg/kg/day. Lipoprotein cholesterol parameters were measured every 4 weeks and clinical chemistries were done at approximately 8-week intervals. Low density lipoprotein cholesterol [LDL-C] was significantly reduced 24-45% at all time periods and total-C was lowered 17-23% at weeks 12, 16, and 24-40 in the timefurone group. Very low density lipoprotein cholesterol [VLDL-C] was increased 68-156% from weeks 40-78 and triglycerides [TG] were significantly elevated 52-220% on weeks 4-16, 24, 28, and 36-78 by timefurone. Timefurone caused small but significant changes in several clinical chemistry parameters including: creatinine, total bilirubin, albumin, glucose, serum glutamic-oxalacetic transaminase, and serum glutamic-pyruvic transaminase during the test. Significant reductions in arterial cholesterol were observed in thoracic aorta (-24%) and carotid arteries (-29%) in treated monkeys when compared to placebo. Arterial cholesterol in treated monkeys was positively correlated to LDL-C (R = 0.54, p less than or equal to 0.05). Timefurone, therefore, appears to have a significant beneficial effect against the development of atherosclerosis in cholesterol-fed male monkeys and possesses excellent potential for clinical experimentation.
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000473:pathology; D001578:Benzopyrans / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000473:pathology; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL / Q000097:blood*; D015243:Cholesterol, VLDL; D004036:Diet, Atherogenic; D008079:Lipoproteins, VLDL / Q000097:blood*; D008252:Macaca fascicularis; D008297:Male; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001578:Benzopyrans; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C046829:timefurone; D002784:Cholesterol