Publications (3)2.78 Total impact
Article: A 6-Month Study on the Toxicity of High Doses of Policosanol Orally Administered to Sprague-Dawley Rats.[show abstract] [hide abstract]
ABSTRACT: Policosanol is a cholesterol-lowering drug purified from sugar cane. Previous toxicological studies have not demonstrated any policosanol-related toxicity, even with long-term oral administration at 500 mg/kg, a dose 1,724 times larger than the maximal therapeutic dose (20 mg/day) recommended to date. The present study was undertaken to investigate the oral toxicity of policosanol administered for 6 months in doses up to 5,000 mg/kg to Sprague-Dawley rats. Animals were randomly distributed in five groups (15 animals per dose per sex): a control and four groups given oral policosanol (50, 500, 2,500, or 5,000 mg/kg). Eight treated rats (6 males, 2 females) died during the study, five of them (4 males, 1 female) from among those receiving the highest dose (5,000 mg/kg). According to necropsy, all deaths were related to gavage manipulation of higher doses. Although the differences were not significant, body weight gain and food consumption in the groups receiving 2,500 or 5,000 mg/kg tended to be lower than in the control group. Nevertheless, no drug-related toxicity symptoms were detected. Analysis of blood biochemistry, hematology, organ weight ratios, and histopathological findings did not show significant differences compared with controls, nor any tendency with the dose. Therefore, the present study did not show any new evidence of oral toxicity of policosanol, and the findings observed were a consequence of long-term administration by gastric gavage of the highly concentrated suspensions needed to reach the higher doses. It is concluded that policosanol chronically administered by the oral route is safe and that no drug-related toxicity was demonstrated.Journal of medicinal food 02/2001; 4(2):57-65. · 1.39 Impact Factor
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ABSTRACT: D-003 is a mixture of very long chain aliphatic acids purified from sugar cane wax with cholesterol-lowering effects. The present study was undertaken to investigate the in vivo cytotoxic and genotoxic potential of D-003 using three established assays: bone marrow micronucleus, sperm morphology, and single cell gel electrophoresis (Comet) assay. In a first experimental series, CEN/NMRI mice (6-8 animals per sex per group) were administered D-003 by gastric gavage at 5, 50, or 500 mg/kg for 90 days, then sacrificed 24 hours after the last administration. The effects on bone marrow micronucleus were evaluated only in female mice. D-003 (5-500 mg/kg) did not increase the frequency of micronucleated polychromatic erythrocytes, nor the ratio of polychromatic to normochromatic erythrocytes, compared with the controls. The assessment of the effects on sperm morphology showed that D-003 did not change the sperm count or the frequency of all types of abnormal head shapes, compared with the controls. In a second series, the micronucleus assay was performed in mice of both sexes given 2,000 mg/kg for 6 days. Likewise, in this series, neither cytotoxic nor genotoxic effects were found. Finally, five male Sprague-Dawley rats were treated with D-003 (1,250 mg/kg) by oral gavage for 90 days, and Comet assay on liver cells was performed. No single-strand breaks or alkali-labile site induction on DNA was observed. These results indicate that D-003 does not show evidence of cytotoxic or genotoxic activity on either somatic or germ cells in rodents.Journal of medicinal food 02/2001; 4(2):85-91. · 1.39 Impact Factor
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ABSTRACT: D-003 is a mixture of higher aliphatic primary acids purified from sugar cane wax (Saccharum officinarum) with cholesterol-lowering and antiplatelet effects experimentally proven. The present work reports the results of two studies investigating the acute and subchronic oral toxicity of D-003 in rats. Oral acute toxicity of D-003 (2000 mg/kg) was investigated according to the Acute Toxic Class (ATC) method (an alternative for the classical LD50 test), which was performed in Wistar rats. The results obtained in this study defined D-003 oral acute toxicity as unclassified. In the subchronic study, rats of both sexes were orally treated with D-003 at 50, 200 and 1250 mg/kg for 90 days. At this time, animals were sacrificed. No evidence of treatment-related toxicity was detected during the study. Thus, data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that D-003 orally administered to rats was safe and that no drug-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg) and subchronic (1250 mg/kg) studies.Toxicology Letters.