Toxicol Lett 1994 Aug;73(2):81-90. Toxicity of policosanol in beagle dogs: one-year study. Mesa AR, Mas R, Noa M, Hernandez C, Rodeiro I, Gamez R, Garcia M, Capote A, Aleman CL. Centro de Productos Naturales, Centro Nacional de Investigaciones Cientificas, Havana City, Cuba.
Policosanol is a new chemical entity composed of 8 higher aliphatic alcohols obtained from sugar cane (Saccharum officinarum), L. wax, whose cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers and patients with type II hypercholesterolemia. This study investigated the oral toxicity of policosanol administered for 52 weeks to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in 3 experimental groups (4 animals/group): a control and 2 treated groups receiving policosanol at 30 and 180 mg/kg daily (7 days/week) by gavage. No mortality was observed in any group. Overall, policosanol was well tolerated throughout the study and no toxic symptoms were observed. All groups showed similar weight gain and food consumption. Lipid profile determinations showed that policosanol decreased total cholesterol by 20% approximately from 8 to 52 weeks. Cholesterol-lowering effects did not wear off during the study, thus demonstrating the persistence of the effectiveness. Triglycerides and high density lipoprotein-cholesterol (HDL-C) were not changed significantly. No blood biochemistry or histopathological disturbances attributable to treatment were observed. This study has shown that no drug-related toxicity was induced by policosanol administered up to 180 mg/kg/day for 52 weeks to beagle dogs. Since this dose is approximately 620 times higher than the maximal recommended therapeutic dose (20 mg/day) it indicates a good safety margin of this product.
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Food Chem Toxicol 1994 Jun;32(6):565-75. Effects of policosanol chronically administered in male monkeys (Macaca arctoides). Rodriguez-Echenique C, Mesa R, Mas R, Noa M, Menendez R, Gonzalez RM, Amor AM, Fraga V, Sotolongo V, Laguna A. Department of Pharmacology and Toxicology, National Center for Scientific Research, Havana City, Cuba.
Policosanol, administered orally, has shown a cholesterol-lowering effect in different experimental models. Because lipid-lowering therapy is administered chronically, it is necessary to know the effects of these drugs after long-term administration. 18 adult male Macaca arctoides monkeys were used to study the cholesterol-lowering effects and possible toxicity produced by oral administration of policosanol (0.25, 2.5 and 25 mg/kg) for 54 wk. After 8 wk, a significant reduction of serum total cholesterol and low-density lipoprotein cholesterol was observed in policosanol-treated animals when compared with the controls; this effect persisted throughout the study. The animals' behavioural repertoire, physical condition, haematology and blood biochemistry, as well as spermiogram analysis and electrocardiography, were monitored during the study; ophthalmological and pathological anatomy examinations were performed at the end of the administration period. No drug-related toxicity was detected by any examination. The results gave further evidence of the marked and persistent cholesterol-lowering effects of policosanol that had been observed in different experimental models. There was a significant reduction of spontaneous aortic atherosclerotic lesions in treated animals compared with controls. Policosanol (0.25-25 mg/kg) administered orally for 54 wk brought about a persistent reduction in blood cholesterol levels and was very safe and well tolerated during long-term administration.
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Prostaglandins Leukot Essent Fatty Acids 1994 May;50(5):249-51. Effect of policosanol on experimental thrombosis models. Carbajal D, Arruzazabala ML, Mas R, Molina V, Valdes S. Department of Pharmacology Center of Natural Products, CNIC, Playa, Habana, Cuba.
Policosanol is a natural product, obtained from sugar cane wax (Saccharum officinarum L.) with which cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers and hypercholesterolemic patients. The effects of policosanol on experimental venous and arterial thrombosis in rats were investigated. Policosanol (25 mg/kg) significantly decreased the thrombus weight, in the venous thrombosis models, the protective effect persisting until 4 h after its oral administration. Policosanol (25 mg/kg single dose) was able to reduce rectal temperature variation induced by arterial thrombosis. Also at the same dose policosanol increased 6-keto-PGF1 alpha serum levels in rats.
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J Pharm Pharmacol 1994 Apr;46(4):282-5. Effect of policosanol on isoprenaline-induced myocardial necrosis in rats. Noa M, Herrera M, Magraner J, Mas R. National Center for Scientific Research, Havana, Cuba.
Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) and octacosanol represents its main component. This study was conducted to examine the effects of policosanol on myocardial necrosis induced by subcutaneous injection of isoprenaline in rats. A significant reduction (P < 0.01) of infarct size, polymorphonuclear cells and mast cells was observed in animals treated with policosanol at 5 or 25 mg kg-1, while animals receiving only acetysalicylic acid pretreatment showed a significant decrease in the infarct area (P < 0.05). No significant differences in polymorphonuclear and mast cells were obtained when compared with positive control data. It is concluded that policosanol delays the evolution of infarction, showing a protective effect on the myocardial necrosis induced by isoprenaline in this experimental model.
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Biol Res 1994;27(3-4):205-8. Cholesterol-lowering effects of policosanol in rabbits. Arruzazabala ML, Carbajal D, Mas R, Molina V, Valdes S, Laguna A. Departamento de Farmacologia, Centro Nacional de Investigaciones Cientificas, La Habana, Cuba.
Policosanol is a natural mixture of higher primary aliphatic alcohols isolated and purified from sugar cane (Saccharum officinarum, L.) wax, whose main component is octacosanol. Policosanol (5-200 mg/kg) orally administered for 4 weeks to normocholesterolemic New Zealand rabbits significantly reduced total cholesterol and low density lipoprotein cholesterol (LDL-C) serum levels in a dose dependent manner. Serum triglyceride levels of treated and control animals were significantly different, but the reduction observed was not dose-dependent. High density lipoprotein cholesterol (HDL-C) levels remained unchanged. Results indicate that the reduction in total cholesterol values induced by policosanol is mainly mediated through a decrease in LDL-C levels.
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Biol Res 1994;27(3-4):199-203. Policosanol inhibits cholesterol biosynthesis and enhances low density lipoprotein processing in cultured human fibroblasts. Menendez R, Fernandez SI, Del Rio A, Gonzalez RM, Fraga V, Amor AM, Mas RM. Centro Nacional de Investigaciones Cientificas, La Habana, Cuba.
Policosanol is a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, that induces cholesterol-lowering effects in experimental models and human beings. When human lung fibroblasts were incubated with policosanol for 48 hours prior to the experiment, a dose dependent inhibition of 14C-acetate incorporation into total cholesterol was observed, whereas labeled mevalonate incorporation was not inhibited. Even when cholesterol synthesis was not strongly inhibited, low density lipoprotein (LDL) processing was markedly enhanced. Thus, LDL binding, internalization and degradation were significantly increased after policosanol treatment. In addition, despite the fact that'cholesterol generation was not inhibited at the lowest dose of policosanol assayed, LDL processing was significantly increased. The current data indicate that policosanol inhibits cholesterol synthesis at the earliest steps of the cholesterol biosynthetic pathway. On the other hand, this study suggests that the increase in LDL processing may be partially explained by the inhibition of cholesterol biosynthesis, even though an sterol-independent mechanism might be responsible for the enhancement of LDL-receptor activity.
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Toxicol Lett 1994 Jan;70(1):77-87. A 12-month study of policosanol oral toxicity in Sprague Dawley rats. Aleman CL, Mas R, Hernandez C, Rodeiro I, Cerejido E, Noa M, Capote A, Menendez R, Amor A, Fraga V, et al. Centro de Productos Naturales, Havana City, Cuba.
Policosanol is a natural mixture of higher aliphatic primary alcohols. Oral toxicity of policosanol was evaluated in a 12-month study in which doses from 0.5 to 500 mg/kg were given orally to Sprague Dawley (SD) rats (20/sex/group) daily. There was no treatment-related toxicity. Thus, effects on body weight gain, food consumption, clinical observations, blood biochemistry, hematology, organ weight ratios and histopathological findings were similar in control and treated groups. This study supports the wide safety margin of policosanol when administered chronically.
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Teratog Carcinog Mutagen 1994;14(3):107-13. Teratogenic and reproductive studies of policosanol in the rat and rabbit. Rodriguez MD, Garcia H. Department of Pharmacology and Toxicology, National Center for Scientific Research, Havana, Cuba.
The present studies evaluated the teratogenic potential and reproductive toxicity of Policosanol, a new hypocholesterolemic drug. Policosanol was administered by oral gavage to Sprague-Dawley rats and New Zealand White rabbits during the period of organogenesis at dosages up to 500 and 1,000 mg/kg/day, respectively. There was no evidence of teratogenicity or any other embryonal toxicity. In a fertility and reproductive study female rats were treated with Policosanol by oral gavage at dosages up to 500 mg/kg/day, 2 weeks prior to mating and throughout mating and pregnancy to day 21 of lactation. Males were given treatment 60 days before and during mating. Reproductive parameters of mothers were normal. There was no evidence that treatment affected the survival, postnatal growth, or behavior of the offspring. No maternal treatment-related adverse side effects occurred in these studies. It is concluded that Policosanol was not teratogenic in either rats or rabbits, nor did it induce reproductive toxicity in rats.
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Int J Clin Pharmacol Res 1994;14(1):27-33. Effects of successive dose increases of policosanol on the lipid profile of patients with type II hypercholesterolaemia and tolerability to treatment. Pons P, Rodriguez M, Robaina C, Illnait J, Mas R, Fernandez L, Fernandez JC. Plaza Polyclinical Centre, Havana, Cuba.
This randomized, double-blind, placebo-controlled study was conducted in 22 patients with type II primary hypercholesterolaemia to investigate the efficacy, safety and tolerability of two successive dose increases of policosanol. Patients with elevated serum low-density-lipoprotein cholesterol (LDL-C) and total cholesterol after a diet-only period received randomly, under double-blind conditions, placebo or policosanol at 5 mg once-a-day for 8 weeks. After this period, dosage was doubled to 5 mg twice-a-day for the next 8 weeks and then again doubled to 10 mg twice-a-day. It was found that the LDL-C was reduced significantly by 11.3%, 21.9% and 31.2%, while total cholesterol was also reduced significantly by 8%, 14.1% and 23% respectively in these three periods. Serum high-density-lipoprotein cholesterol (HDL-C) was increased by 7.8%, 7.2% and 8.7%, respectively, while in the placebo group a downward shift was observed. The LDL-C to HDL-C ratio was reduced significantly by 15.3%, 25.6% and 34.6%, while the total cholesterol to HDL-C ratio was also reduced significantly by 12.5%, 18.4% and 27.1%, respectively. Triglycerides and VLDL-C values did not change significantly. The reduction of LDL-C, total cholesterol, LDL-C to HDL-C, and total cholesterol to HDL-C ratios showed a dependence on the successive dose increases. Policosanol was very well tolerated. No patient discontinued the trial. No disturbances of clinical or blood biochemistry variables attributable to treatment were observed. Adverse effects reported were mild and transient, and no significant differences between groups were found.
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Teratog Carcinog Mutagen 1994;14(5):239-49. Carcinogenicity of policosanol in Sprague Dawley rats: a 24 month study. Aleman CL, Mas Ferreiro R, Noa Puig M, Rodeiro Guerra I, Hernandez Ortega C, Capote A. Center of Natural Products, National Center for Scientific Research, Havana City, Cuba.
The effects of policosanol (50-500 mg/kg) administered orally for 24 months to Sprague Dawley rats of both sexes were investigated. No differences related to daily clinical observations, weight gain, food consumption, or mortality (survival analysis) between groups were found. Histopathological study showed that the frequency of the occurrence of non-neoplastic and neoplastic (benign and malignant) lesions was similar in the control and policosanol-treated groups. The lesions observed in this study were similar to the spontaneous lesions reported in this species in previous studies. Since no drug-related increase in the occurrence of malignant or benign neoplasms was found, nor acceleration in tumors growth in any specific group was observed, this study shows no evidence of policosanol induced carcinogenicity in this strain of rats.
