Aims The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. Methods The effect of policosanol (5 and 10 mg day x1 ) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 69 subjects. LDL-C samples isolated at baseline and after 8 weeks were subjected to in vitro tests of LDL-C oxidation. We tested the susceptibility of LDL-C to lipid peroxidation in a cell-free system by the addition of copper ions as well as in a more physiological system, macrophage-mediated oxidation.Results At baseline all groups were well matched regarding all variables. After 8 weeks of therapy policosanol administered at 5 and 10 mg, signi®cantly and in a dosedependent manner increased the lag phase of conjugated diene generation (meants.d.) from 83.79t29.16 min to 94.90t25.50 min (5 mg day x1 ) and from 82.74t17.16 min to 129.89t35.71 min (10 mg day x1 ), while in the placebo group LDL-C oxidation did not change signi®cantly. Policosanol (10 mg day x1 ), but not placebo, signi®cantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed signi®cant differences. Macrophage mediatedoxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day x1 ) signi®cantly lowered malondialdehyde (MDA) generation from 8.50t0.91 to 5.76t1.01 nmol mg x1 protein. Comparison with placebo after 5 and 10 mg day x1 showed signi®cant differences. Policosanol signi®cantly lowered total cholesterol by 10.5% (5 mg day x1 ) and 12.4% (10 mg day x1 ) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day x1 ) increased HDL-C by 15.2%. Five subjects withdrew from the study, none because of adverse experiences. No clinical or blood biochemical drug-related disturbances were found. Conclusions The present study demonstrated that policosanol administered within its therapeutic dosage for lowering cholesterol (5 and 10 mg day x1 ), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.

SummaryA reference database comprising body weight gain, exploratory activity, hot plate response, serum biochemistry, haematology, organ weight (%) and a complete anatomopathological study containing non-neoplastic and neoplastic lesions over 1200 Sprague-Dawley rats from 6 to 32 months is described. Comparisons between age and sex were analysed.Keywords Database; Sprague-Dawley rats, biological parameters Toxicology laboratories and other research institutions collect large bodies of reference data in order to support drug and chemical toxicity testing. However, many of these databases contain either a relatively small number of animals, a limited number of parameters, or poorly defined limitations by age, all of which limit their usefulness on a routine basis. In addition, it is often unclear whether the same test method was used throughout the data collection period. In our laboratory, we have set up and maintain a large reference database. The database covers not only the main physiological indicators, including results of the anatomicopathological studies, but also the major life span of this species. The data were classified into three main age groups, <6,6-18 and 18-32 months according to Wolford et a1. (1986), and sex. The present results correspond to data of special sentinel groups from different preclinical toxicological evaluations performed in our laboratory during the last 7 years.

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Different medicinal plants are widely used in Cuba and Mexico to treat several disorders. This paper reports in vitro inhibitory effects on the P450 system of herbal products commonly used by people in Cuba and Mexico in traditional medicine for decades. Experiments were conducted in human liver microsomes. The catalytic activities of CYP1A1/2, 2D6, and 3A4 were measured using specific probe substrates. The Heliopsis longipes extract exhibited a concentration-dependent inhibition of the three enzymes, and similar effects were produced by affinin (an alkamide isolated from the H. longipes extract) and two catalytically reduced alkamides. Mangifera indica L. and Thalassia testudinum extracts, two natural polyphenol-rich extracts, diminished CYP1A1/2 and 3A4 activities, but not the CYP2D6 activity. These results suggest that these herbs inhibit the major human P450 enzymes involved in drug metabolism and could induce potential herbal-drug interactions.