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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

In vitro and in vivo study of octacosanol metabolism.

BACKGROUND: Policosanol is a mixture of very-long-chain aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects, whose main component is octacosanol. Scarce data about the metabolism of octacosanol and the other fatty alcohols composing policosanol have been published. METHODS: Human fibroblasts were cultured in presence of (3)H-octacosanol during 0.5, 2 and 4 h. Lipid extracts were analyzed by thin layer chromatography, and the spots corresponding to octacosanol and octacosanoic acid were identified comparing with authentic standards. Spots were scraped, transferred to vials and radioactivity was measured. For corroborating the presence of octacosanol and octacosanoic acid, samples were analyzed by gas chromatography-mass spectrometry (GC-MS). The in vivo study of octacosanol metabolism was conducted in rats and Macaca arctoides monkeys. Rats were orally administered with policosanol (60 mg/kg) and free octacosanol and octacosanoic acid were identified in liver and plasma by GC-MS at various time intervals. Monkeys were orally and endovenously treated with policosanol (10 mg/kg) and the presence of free octacosanol, octacosanoic acid and some chain-shortened FA was investigated. RESULTS: When fibroblasts were cultured in presence of (3)H-octacosanol, three spots were found: a first one corresponded to octacosanoic acid, a second to octacosanol and a third one remained unidentified. The radioactivity on the spot of octacosanoic acid slightly decreased throughout the incubation but increased in the third spot. Octacosanol and free octacosanoic acids were also identified in plasma of monkeys orally administered with policosanol. In addition, plasma samples showed free saturated acids, palmitic acid being the most abundant, followed by oleic and mystiric acids. Unsaturated acids (oleic and palmitoleic) were also observed. CONCLUSIONS: The present study demonstrates that octacosanoic acid is formed after incubation of fibroblast cultures with (3)H-octacosanol and after oral dosing with policosanol to rats. In addition, we demonstrated that shortened saturated (myristic, palmitic and stearic) and unsaturated (oleic, palmitoleic) FA are also formed after oral dosing with policosanol to monkeys. The present results are consistent with the fact that octacosanol metabolism is linked to FA metabolism via beta-oxidation, but further studies need to explore the occurrence of more metabolites proving such hypothesis.[1]


  1. In vitro and in vivo study of octacosanol metabolism. Menéndez, R., Marrero, D., Más, R., Fernández, I., González, L., González, R.M. Arch. Med. Res. (2005) [Pubmed]
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