Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Atherosclerosis 1985 Sep
PMID: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. 386 22

Timefurone was evaluated in several animal models for cholesterol-lowering and anti-atherosclerotic activity. In normal male rats, a dose-response study with timefurone (3, 10, 30, 50 and 100 mg/kg/day) was conducted for 7 days. Significant activity was observed only at 50 and 100 mg/kg/day, where very low and low density lipoprotein cholesterol [(VLDL + LDL)-C] and total-C levels were reduced (mean 27 and 20%). High density lipoprotein cholesterol (HDL-C) was lowered 24% by the high timefurone dose. Timefurone (10, 20, 50 and 100 mg/kg/day in the diet) was then examined in normocholesterolemic SEA japanese quail. beta-lipoprotein cholesterol (VLDL + LDL)-C was reduced at all doses (mean 58%), while alpha-lipoprotein cholesterol (HDL-C) was elevated by all doses of timefurone (mean 45%). Male weanling rats made moderately hypercholesterolemic represented a 3rd phase of timefurone (2.5, 5, 10, 20, 50, 100 mg/kg/day) testing. After 4 days of drug treatment, marked hypocholesterolemic activity was observed for (VLDL + LDL)-C (mean decrease 49%) and total-C (mean 33%). HDL-C levels were increased with 10 and 100 mg/kg/day doses. Timefurone (25 and 100 mg/kg/day in the diet) also caused a significant reduction in atherosclerotic development in hypercholesterolemic SEA japanese quail. Atherosclerotic involvement (determined by visual assessment of plaque), arterial weight, and arterial cholesterol (total and mg/g artery) were clearly lowered by both doses of timefurone. There was no evidence of significant drug toxicity in any of these experiments. On the basis of these data, timefurone has excellent therapeutic potential and additional study of the drug's hypocholesterolemic and anti-atherosclerotic properties appears warranted.
Atherosclerosis 1985 Sep
PMID:Evaluation of timefurone, a new anti-atherosclerotic drug, for its effects on lipoprotein cholesterol in male SEA Japanese quail and rats. 386 23