Primary Spinal Epidural Lymphoma As a Cause of Spontaneous Spinal Anterior Syndrome: A Case Report and Literature Review.

Background Primary spinal epidural lymphoma (PSEL) is one of the rarest categories of tumors. Spinal cord compression is an uncommon primary manifestation and requires to be treated with surgery for the purpose of diagnosis and decompression. Case Presentation A 45-year-old man presented with a new onset thoracic pain and progress to an anterior spinal syndrome with hypoesthesia and loss of thermalgesia. Magnetic resonance image showed a paravertebral mass that produces medullary compression at T3. The patient was taken up to surgery, where the pathology examination showed a diffuse large B-cell lymphoma. Conclusions PSEL is a pathological entity, which must be considered on a middle-aged man who began with radicular compression, and the treatment of choice is decompression and biopsy. The specific management has not been established yet, but the literature suggests chemotherapy and radiotherapy; however, the outcome is unclear.

Maternal nutrition during pregnancy and risk of asthma, wheeze, and atopic diseases during childhood: a systematic review and meta-analysis.

BACKGROUND: Epidemiologic studies suggest a relationship between maternal nutrition during pregnancy and the occurrence of asthma and atopic conditions during childhood. However, individual study results are conflicting. The objective of this meta-analysis was to critically examine the current evidence for an association between nutrition (dietary patterns, food groups, vitamins, or oligo-elements) ingestion during pregnancy and asthma, wheeze, or atopic conditions in childhood. METHODS: The inclusion criteria were as follows: (i) systematic recording of diet during the gestational period and (ii) documentation of asthma, wheezing, eczema, or other atopic disease in the offspring. The primary outcomes were prevalence of asthma or wheeze among the offspring during childhood; and secondary outcomes were prevalence of eczema, allergic rhinitis, or other atopic conditions. RESULTS: We found 120 titles, abstracts, and citations, and 32 studies (29 cohorts) were included in this analysis. Data on vitamins, oligo-elements, food groups, and dietary patterns during pregnancy were collected. A meta-analysis revealed that higher maternal intake of vitamin D [odds ratio (OR) = 0.58, 95% confidence interval (CI) = 0.38-0.88], vitamin E (OR = 0.6, 95% CI = 0.46-0.78), and zinc (OR = 0.62, 95% CI = 0.40-0.97) was associated with lower odds of wheeze during childhood. However, none of these or other nutrients was consistently associated with asthma per se or other atopic conditions. CONCLUSIONS: Current evidence suggests a protective effect of maternal intake of each of three vitamins or nutrients (vitamin D, vitamin E, and zinc) against childhood wheeze but is inconclusive for an effect on asthma or other atopic conditions.

Study of the long-term carcinogenicity potential of D-003, a mixture of high molecular weight sugarcane wax acids, in mice.

D-003, a mixture of high aliphatic primary acids purified from sugar cane wax, has shown cholesterol-lowering, anti-platelet and antioxidant effects. Previous data demonstrated that D-003 was not toxic or carcinogenic when given orally to Sprague-Dawley rats up to 1500 mg/kg. This study investigated the potential long-term oral carcinogenicity of D-003 in a second rodent species. OF1 mice of both sexes were randomized into 4 groups treated for 18 months: a vehicle control group and three groups treated with D-003 at 50, 500 and 1500 mg/kg, respectively, orally gavaged 6 days per week. Mortality, clinical symptoms, weight gain, food consumption, organ weight, blood indicators and tumour incidence did not show significant differences between control and treated groups. D-003 did not increase the frequency of neoplastic or non-neoplastic lesions with respect to the controls. Lesions observed in the study were consistent with spontaneous lesions reported for this specie. It can be concluded that D-003 did not result toxic or carcinogenic when given orally to OF1 mice for 18 months and that the highest dose was a NOAEL, consistent with results of the oral carcinogenicity study of D-003 in rats.

Long-term carcinogenicity of D-003, a mixture of high molecular weight acids from sugarcane wax, in Sprague Dawley rats: a 24 months study.

D-003 is a mixture of high molecular weight sugarcane wax aliphatic primary acids with cholesterol-lowering, anti-platelet and antioxidant effects. This study investigated the long-term oral toxicity and carcinogenicity of D-003 in Sprague Dawley rats of both sexes, randomly distributed into four groups: a control group, treated only with the vehicle, and three treated with D-003 (50, 500 and 1500 mg/kg). All treatments were given orally for 24 months. Mortality (survival analysis), clinical symptoms, weight gain, food consumption, organ weights, time-to-tumour or tumour incidence data were not shown between group differences or trends. With the exception of serum cholesterol levels, lower in D-003-treated groups (500 and 1500 mg/kg) than in the controls, no other difference in blood indicators was found. D-003 did not increase the frequency of neoplastic and non-neoplastic lesions compared with the controls. The occurrence of all malignant and mammary tumours in D-003-treated females was lower than in the controls. The lesions observed were consistent with spontaneous lesions reported in this species. In conclusion, D-003 is not toxic or carcinogenic when given orally to Sprague Dawley rats up to 1500 mg/kg for 2 years, and 1500 mg/kg was a not-observable effect dose.

In Vitro effect of D-004, a lipid extract of the ground fruits of the Cuban royal palm (Roystonea regia), on rat microsomal lipid peroxidation.

D-004 is a lipid extract of the fruits of the Cuban royal palm (Roystonea regia) containing a mixture of saturated fatty acids. D-004 inhibits prostate hyperplasia (PH) induced with testosterone, in rodents. Since fatty acids inhibit lipid peroxidation (LP), this study investigated whether D-004 prevents in vitro LP. D-004 (0.9-1000 microg/mL) markedly and dose-dependently inhibited in vitro iron-induced LP in native brain and liver microsomes. D-004 showed hydroxyl radical scavenging activity, which could explain partially its antioxidant effect on microsomal iron-induced LP, but it was unable to scavenge superoxide and ABTS radicals, indicating a limited radical scavenging activity. Also, D-004 inhibited CCl4-mediated LP in active liver microsomes through a decreased generation of radical species rather than a radical trapping action on CCl(4)-derived radical species. D-004 also inhibited lipooxygenase (LOX) and cyclooxygenase (COX) activities, and the generation of protein-associated carbonyl groups after LP. Since increased oxidative stress has been linked to PH, the antioxidant effect of D-004 shown here could contribute to explaining its beneficial effects on T-induced PH in rodents. Nevertheless, this study shows only in vitro results. Further studies should investigate whether D-004 also exhibits antioxidant effects in vivo.

Evaluation of the genotoxic potential of Mangifera indica L. extract (Vimang), a new natural product with antioxidant activity.

Mangifera indica L. extract (Vimang) consists of a defined mixture of components (polyphenols, terpenoids, steroids, fatty acids and microelements). It contains a variety of polyphenols, phenolic esters, flavan-3-ols and a xanthone (mangiferin), as main component. This extract has antioxidant action, antitumor and immunemodulatory effects proved in experimental models in both in vitro and in vivo assays. The present study was performed to investigate the genotoxicity potential activity of Vimang assessed through different tests: Ames, Comet and micronucleus assays. Positive and negative controls were included in each experimental series. Histidine requiring mutants of Salmonella typhimurium TA1535, TA1537, TA1538, TA98, TA100 and TA102 strains for point-mutation tests and in vitro micronucleus assay in primary human lymphocytes with and without metabolic activation were performed. In addition, genotoxic effects were evaluated on blood peripheral lymphocytes of NMRI mice of both sexes, which were treated during 2 days with intraperitoneal doses of M. indica L. extract (50-150 mg/kg). The observed results permitted to affirm that Vimang (200-5,000 microg/plate) did not increase the frequency of reverse mutations in the Ames test in presence or not of metabolic activation. Results of Comet assay showed that the extract did not induce single strand breaks or alkali-labile sites on blood peripheral lymphocytes of treated animals compared with controls. On the other hand, the results of the micronucleus studies (in vitro and in vivo) showed Vimang induces cytotoxic activity, determined as cell viability or PCE/NCE ratio, but neither increased the frequency of micronucleated binucleate cells in culture of human lymphocytes nor in mice bone marrow cells under our experimental conditions. The positive control chemicals included in each experiment induced the expected changes. The present results indicate that M. indica L. extract showed evidences of light cytotoxic activity but did not induce a mutagenic or genotoxic effects in the battery of assays used.

Oral administration of D-003, a mixture of very long chain fatty acids prevents casein-induced endogenous hypercholesterolemia in rabbits.

D-003 is a mixture of very long chain saturated fatty acids (VLCSFA) purified from sugar cane wax with cholesterol-lowering effects proven in animal models and healthy volunteers. D-003 inhibits cholesterol biosynthesis through the regulation of HMG-CoA reductase activity. Rabbits fed diets enriched with casein develop endogenous hypercholesterolemia (EH), making them a very useful model for determining the mechanism of action of drugs affecting lipids. We examined whether D-003 prevented EH. Rabbits were fed a casein diet for 4 weeks, administered simultaneously with D-003 (5, 50, and 100 mg.kg-1.day-1). As expected, nontreated rabbits became hypercholesterolemic; however, as early as 15 days following administration, the treated group (50 and 100 mg.kg-1.day-1) had significantly decreased total cholesterol and low-density lipoprotein cholesterol (LDL-C). Triglycerides were not affected; however, at study completion, HDL-C levels significantly increased at all the doses assayed. D-003 inhibited de novo synthesis of cholesterol, since the incorporation of 3H2O into sterols in the liver and proximal small bowel was significantly depressed. Also, D-003 significantly raised the rate of removal of [125I]-LDL from serum and significantly elevated [125I]-LDL binding activity to liver homogenates. Taken together, these results show that the efficacy of D-003 in reducing casein-derived hypercholesterolemia could involve, at least partially, an inhibition of hepatic cholesterol biosynthesis, which may elicit a decreased cholesterol concentration in hepatocytes, preventing the loss of hepatic LDL receptors induced by casein administration. However, since casein-induced hypercholesterolemia is also a consequence of a stimulation of cholesterol absorption in the lumen and an increase of the output of cholesterol associated with LDL, the effect of D-003 on cholesterol absorption and LDL synthesis by the liver should be investigated.

[Neurophysiological diagnosis of lumbosacral radicular compression syndrome from late responses]. / Diagnóstico neurofisiológico del síndrome compresivo radicular lumbosacro a través de las respuestas tardías.

INTRODUCTION: Lumbosacral radicular compression syndrome is a disorder that can affect anyone at some moment in their lives, regardless of their sex, age and profession. It appears more frequently in specific groups of people. Late responses constitute neurophysiological studies that allow evaluation of the functional state of the proximal portions of the peripheral nervous system, which are affected to a greater or lesser extent in the course of this pathological state. AIMS. To determine the usefulness of the F wave and H reflex in lumbosacral compressive radiculopathies at L5 and S1. PATIENTS AND METHODS: We examined 100 patients who had been clinically and imagenologically diagnosed as suffering from lumbosacral compressive radiculopathy, which was classified as being L5 and S1. Late responses (F wave and H reflex) were performed and they were compared with a group made up of 74 normal subjects. RESULTS: In patients with L5 radiculopathy, the F wave was abnormal in 66.6% of the cases, where a reduction in the percentage of waves obtained from patients and prolonged minimum, average and maximum latencies predominated. In the case of patients with S1 lumbosacral compressive radiculopathies, 77.5% presented H reflex alterations and the main abnormalities were detected as being the prolongation of reduced amplitude latencies and the absence of response. CONCLUSIONS: The F wave and H reflex are useful tools for evaluating patients with compressive radiculopathies at L5 and S1, respectively.

Inhibition of rat lipoprotein lipid peroxidation by the oral administration of D003, a mixture of very long-chain saturated fatty acids.

Previous results have demonstrated that policosanol, a mixture of aliphatic primary alcohols isolated and purified from sugar cane wax, whose main component is octacosanol, inhibited lipid peroxidation in experimental models and human beings. D003 is a defined mixture of very long-chain saturated fatty acids, also isolated and purified from sugar cane wax, whose main component is octacosanoic acid followed by traicontanoic, dotriacontanoic, and tetracontanoic acids. Since very long-chain fatty acids are structurally related to their corresponding alcohols, we investigated the effect of oral treatment with D003 (0.5, 5, 50, and 100 mg/kg) over 4 weeks in reducing the susceptibility of rat lipoprotein to oxidative modification. The combined rat lipoprotein fraction VLDL + LDL was subjected to several oxidation systems, including those containing metal ions (CuSO4), those having the capacity to generate free radicals 2,2-azobis-2-amidinopropane hydrochloride (AAPH), and a more physiological system (resident macrophages). D003 (5, 50, and 100 mg/kg) significantly inhibited copper-mediated conjugated-diene generation in a concentration-dependent manner. D003 increased lag phase by 53.1, 115.3, and 119.3%, respectively, and decreased the rate of conjugate-diene generation by 16.6, 21.5, and 19.6%, respectively. D003 also inhibited azo-compound initiated and macrophage-mediated lipid peroxidation as judged by the significant decrease in thiobarbituric acid reactive substance (TBARS) generation. In all the systems the maximum effect was attained at 50 mg/kg. There was also a parallel attenuation in the reduction of lysine amino groups and a significant reduction of carbonyl content after oxidation of lipoprotein samples. Taken together, the present results indicate that oral administration of D003 protects lipoprotein fractions against lipid peroxidation in the lipid as well in the protein moiety.

Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture of very long chain saturated fatty acids.

The present study was undertaken to investigate the effects of D003, a mixture of very long chain saturated fatty acids isolated and purified from sugar cane wax, on cholesterol biosynthesis in cultured fibroblasts. Cholesterol biosynthesis is regulated through feedback regulation of at least two sequentially acting enzymes, 3-hydroxy-3-methyl coenzyme A (HMG-CoA) synthase and reductase. They are up-regulated when sterol levels fall and down-regulated when sterol levels rise. The exposure of cultured fibroblasts to a lipid-depleted medium (LDM) and D003 (0.05-50 microg ml(-1)) for 12 h inhibited, in a dose-dependent manner, cholesterol biosynthesis from 14C-labelled acetate (33-68%). The addition of D003 at concentrations inhibiting cholesterol biosynthesis from labelled acetate significantly decreased incorporation of radioactivity from 3H2O into sterols, but not from 14C-mevalonate. These data indicate that D003 inhibits cholesterol biosynthesis by interfering with early steps of cholesterol biosynthetic pathway. We reasoned that D003 acts directly on HMG-CoA reductase, the main regulatory enzyme of cholesterol biosynthetic pathway. However, when enzyme activity was measured in cell extracts in the presence of various concentrations of D003 (0.5-50 microg ml(-1)), reductase activity was not inhibited. Thus, there was no evidence for a competitive or non-competitive inhibition of enzyme activity by D003. Treatment with D003 significantly suppressed (68%) the enzyme up-regulation when cells were cultured in LDM, which suggests a depression of de novo synthesis of HMG-CoA reductase and/or a stimulation of its degradation. However, since the suppressive action of D003 on cholesterol biosynthesis was observed in metabolic conditions under which synthase up-regulation was also enhanced, we cannot rule out a possible effect of D003 on HMG-CoA synthase. Thus, further studies are needed to clarify the precise mechanism of the inhibitory effect of D003 on cholesterol biosynthesis.

Antioxidant effects of D002 on the in vitro susceptibility of whole plasma in healthy volunteers.

BACKGROUND: It has been recently shown that oral administration of D002, a mixture of higher aliphatic primary alcohols isolated from beeswax, inhibits rat microsomal lipid peroxidation. This justified the present attempt to investigate whether D002 also exerts antioxidant effects in humans. METHODS: The effects of D002 on lipid peroxidation were studied in a double-blind, randomized, placebo-controlled trial conducted in 50 healthy volunteers. Unfractionated plasma samples at baseline and at 12 weeks were subjected to in vitro copper-induced lipid peroxidation and conjugated diene generation was monitored by changes of optical density. RESULTS: The oral treatment with D002 (50 mg/day) not only significantly prolonged (p <0.001) lag time before the onset of conjugated diene formation compared with that of baseline but also increased (p <0.05) lag phase when compared with placebo group. In fact, in the D002 group the lag-phase of oxidation was prolonged 1.5-fold. D002 oral treatment decreased TBARS and increased plasma total antioxidant status (TAS) (p <0.01). CONCLUSIONS: Because prooxidant states have been linked to normal senescence and some age-related diseases, the present data suggest that D002 may find a use in preventing age-related diseases as a dietary natural antioxidant supplement.

Developmental impairment of auditory evoked N1/P2 component in rats undernourished in utero: its relation to brain serotonin activity.

In utero undernourishment produces an elevation of L-tryptophan and serotonin in the brain, including the auditory cortex (A1), such changes seem to be related to an increase in the free fraction (FFT) of plasma L-tryptophan that is transported into the brain through the blood-brain barrier, where it is taken up by serotonergic neurons for serotonin synthesis. Our observations support that FFT has a positive correlation with L-tryptophan (L-Trp) and serotonin levels in the auditory cortex (r=0.95 and 0.82, respectively). Interestingly, a decreased intensity dependence of the auditory evoked N1/P2 component was found in gestationally undernourished animals during their postnatal development. The N1/P2 component had a negative correlation (r=0.81) with A1 serotonin, such that it reflects changes in the neurotransmitter concentration. The present observations suggest a relevant role of serotonin in modulating the activity of the auditory cortex. Since the N1/P2 component is mainly associated with the activity of A1 neurons, it may well be that perception of auditory information is impaired during this developmental period, in the early undernourished animals, possibly affecting cognitive processes. This may be relevant to humans since low birth weight babies that also suffered gestational undernourishment (fetal-placental insufficiency) present an increase in plasma FFT from birth up to 3 months of age. These findings support that the plasma FFT and the intensity dependence of the auditory evoked N1/P2 component relate one another and may be markers of changes of the brain serotonergic activity.

Policosanol modulates HMG-CoA reductase activity in cultured fibroblasts.

BACKGROUND: Cholesterol biosynthesis is strictly controlled by 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase. METHODS: Transfer of cultured fibroblasts to a lipid-depleted medium (LDM) up-regulates the enzyme levels. This, in turn, is followed by an accelerated biosynthesis of cholesterol. RESULTS: Exposure of Vero fibroblasts to LDM and policosanol (0.5-50 microg/mL), a new cholesterol-lowering drug purified from sugarcane (Saccharum officinarum L.) wax, decreased in a dose-dependent manner cholesterol biosynthesis from [14C]-acetate and 3H-water, but not from [14C]-mevalonate. CONCLUSIONS: This suggests an effect on HMG-CoA reductase, the rate-controlling enzyme in cholesterol biosynthesis. When enzyme activity was measured in the presence of various concentrations of policosanol (0.5-50 microg/mL), reductase was not suppressed. Therefore, there was no evidence for a competitive or noncompetitive inhibition of enzyme activity. However, after treatment of intact cells with policosanol (50 microg/mL) in the presence of LDM, a suppressive effect on enzyme activity was observed, suggesting a modulatory effect of policosanol on reductase activity. The previous inhibition of enzyme up-regulation by policosanol suggests to date a depression of de novo synthesis of HMG-CoA reductase and/or stimulation of its degradation. However, the exact mechanism by which policosanol inhibits the activity of HMG-CoA reductase still remains unclear. Further studies are needed to clarify the precise mechanism of its inhibitory action on cholesterol biosynthesis.

Effects of D-002 on Lipid Peroxidation in Older Subjects.

D-002 is a mixture of higher aliphatic alcohols isolated from beeswax that inhibits rat microsomal lipid peroxidation in vitro and in vivo. This study was undertaken to investigate whether D-002 also inhibits lipid peroxidation in older subjects. The free radical theory of aging suggests that progressive defects in the protection against free radical reactions leads to progressive deleterious effects of free radicals on cells and tissues. This free radical damage has been implicated in several pathophysiological processes associated with the chronic degenerative diseases that occur with aging. Forty-eight older subjects were randomly assigned, in a double-blind fashion, to receive placebo or D-002 tablets (50 mg/day) once daily. At baseline, D-002 and placebo groups were well matched regarding several variables. D-002 significantly reduced the susceptibility of nonfractionated plasma samples to copper-mediated lipid peroxidation. It also significantly increased the length of the lag phase (P <.001) and the total antiioxidant status (P <.05) compared with baseline and placebo. In addition, D-002 significantly decreased malondialdehyde levels (expressed in terms of thiobarbituric acid reactive substances (TBARS, P <.001) compared with baseline, but not with placebo. No significant changes on lipid peroxidation parameters were observed in the placebo group. We conclude that D-002 treatment may be useful to prevent or manage certain pathophysiological conditions in the elderly.

Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro.

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(-1) 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, significantly and in a dose-dependent manner increased the lag phase of conjugated diene generation (mean +/- s.d.) from 83.79+/-29.16 min to 94.90+/-25.50 min (5 mg day(-1)) and from 82.74+/-17.16 min to 129.89+/-35.71 min (10 mg day(-1)), while in the placebo group LDL-C oxidation did not change significantly. Policosanol (10 mg day(-1)), but not placebo, significantly decreased the rate of conjugated diene generation. Comparison with placebo after therapy also showed significant differences. Macrophage mediated-oxidation was also inhibited by policosanol as evident by measuring thiobarbituric acid reactive substances (TBARS). Policosanol (10 mg day(-1)) significantly lowered malondialdehyde (MDA) generation from 8.50+/-0.91 to 5.76+/- 1.01 nmol mg(-1) protein. Comparison with placebo after 5 and 10 mg day(-1) showed significant differences. Policosanol significantly lowered total cholesterol by 10.5% (5 mg day(-1)) and 12.4% (10 mg day(-1)) and LDL-C by 16.7% and 20.2%, respectively. Also, policosanol (10 mg day(-1)) 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(-1)), decreased the susceptibility of LDL-C to lipid peroxidation in vitro.

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002.

The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS). When D002 (5-100 mg/kg body weight) was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46%) occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg) also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40%) and brain (28-44%) microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg) for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans.

Inhibition of rat microsomal lipid peroxidation by the oral administration of D002

The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS). When D002 (5-100 mg/kg body weight) was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46 percent) occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg) also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40 percent) and brain (28-44 percent) microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg) for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans

Oral administration of policosanol inhibits in vitro copper ion-induced rat lipoprotein peroxidation.

Policosanol, a new cholesterol-lowering agent, is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) wax, which prevents the onset of espontaneously and experimentally induced atherosclerotic lesions in experimental models. Because the oxidation of low-density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis, we investigate the effect of policosanol on copper oxidative susceptibility of rat lipoprotein fractions (VLDL + LDL). Rats fed normal diet were treated with policosanol (250-500 mg/kg/day) for up to 4 weeks. EDTA-free lipoprotein particles were oxidized in a cell-free system by the addition of copper ions, and conjugated dienes generation was monitored by changes of optical density at 234 nm. Thiobarbituric acid-reactive substances (TBARS) content and lysine-amino group reactivity were investigated. After administration, there was no change in cholesterol, triglycerides, and phospholipid content of lipoprotein fractions; however, policosanol significantly prolongs the lag time and reduces the propagation rate of diene generation. Also, policosanol reduces TBARS content and increases lysine reactivity in lipoprotein fractions treated with Cu2+. In conclusion, policosanol, in addition to its cholesterol-lowering effect, has other properties that enables it to reduce the potential of lipoprotein to undergo lipid peroxidation. Such effect can be considered of promissory value in the management of atherosclerosis.

Effect of policosanol on in vitro and in vivo rat liver microsomal lipid peroxidation.

Policosanol, a defined mixture of high molecular weight aliphatic alcohol isolated and purified from sugar cane (Saccharum officinarum, L) wax is a new cholesterol-lowering agent effective in experimental models, healthy volunteers, and patients with type II hypercholesterolemia. Also, policosanol prevents the onset of spontaneously- and experimentally-induced atherosclerotic lesions and cerebral ischemia in Mongolian gerbils. Free radicals are linked to many diseases including atherosclerosis and ischemia/ reoxidation cellular injury. Therefore, in this study the authors evaluate the antioxidant activity of policosanol on rat liver microsomes. The extent of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS). When policosanol was administered orally (100 and 250 mg/kg) for up to 4 weeks, a partial prevention of rat in vitro microsomal lipid peroxidation was noted. The formation of TBARS in microsomes isolated from treated rats was significantly decreased by about 50%, when peroxidation was initiated by Fe3+/ADP/ NADPH, Fe2+/ascorbate and CCl4/NADPH-generating system. Also, oral administration of policosanol in rats provides a partial inhibition of lipid peroxidation, but the mechanism supporting such effect remains to be elucidated. This beneficial effect of policosanol on membrane lipid peroxidation may be useful in protecting to some extent against free radical-associated diseases.

Cholesterol-lowering effect of policosanol on rabbits with hypercholesterolaemia induced by a wheat starch-casein diet.

The effect of policosanol, a mixture of high-molecular-weight aliphatic alcohols isolated from sugarcane wax, on casein-induced hypercholesterolaemia in rabbits was studied. When policosanol was administered by the oral route once daily for 30 d (50 mg/kg) the increases in plasma total cholesterol and LDL-cholesterol (LDC-C) were significantly reduced when compared with the control group. The incorporation of 3H2O into sterols in the liver was significantly depressed, suggesting inhibition of hepatic cholesterol biosynthesis. The oral administration of policosanol raised the rate of removal of 125I-labelled LDL from serum. Kinetic parameters calculated following injection of [125I]LDL showed than in casein-fed rabbits, the terminal half-life (t1/2) was significantly decreased after policosanol treatment. The hepatic LDL-binding activity was increased after policosanol administration which suggested that the enhanced clearance was due, at least in part, to increased receptor-mediated uptake of LDL by the liver. Considered together, these results suggest that policosanol can significantly reduce the increase of plasma LDL-C in rabbits fed on a wheat starch-casein diet by reducing cholesterol biosynthesis in the liver. Such an effect could account for the enhancement of LDL catabolism through the receptor-mediated pathway.