Smoking attenuates the negative association between carotenoids consumption and colorectal cancer risk.

OBJECTIVES: Consumption of vegetables and fruits, physical activity, obesity and caloric intake are all strongly related to the risk of colorectal cancer (CRC). The association between dietary intake of carotenoids from vegetables/fruits and risk of CRC in the context of cigarette smoking was studied in a nutritionally diverse population. METHODS: The study included 1,817 age sex residence-matched case-control pairs from a population-based study in Northern Israel. Data were acquired by food-frequency questionnaire. Individual intake of carotenoid isomers was calculated using an Israeli food content database. Odds ratios (ORs) were calculated using conditional logistic regression models adjusted for known risk factors. RESULTS: Strong inverse associations were found with consumption of 9-cis-beta-carotene (OR = 0.35, 0.26-0.47), all-trans-beta-carotene (OR = 0.58, 0.44-0.76), cis-beta-cryptoxanthin (OR = 0.67, 0.50-0.90), all-trans-zeaxanthin (OR = 0.64, 0.48-0.86), and lutein (OR = 0.74, 0.57-0.96). Lycopene (OR = 2.22, 1.71-2.89) and all-trans-beta-cryptoxanthin (OR = 2.01, 1.48-2.73) were associated with increased risk of CRC. Inverse associations of most carotenoids with CRC, demonstrated in non-smokers, were much attenuated or reversed in past or current smokers with a highly significant interaction term. CONCLUSIONS: Consumption of most dietary carotenoids was found to be strongly associated with reduced risk of CRC. However, smoking significantly attenuated or reversed this observed protective effect on CRC occurrence. Smokers should be advised that smoking also hampers the potential health promoting effects of high fruit and vegetable consumption.

Natural beta-carotene for the prevention of post-ERCP pancreatitis.

OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly used procedure. Pancreatitis is its most common complication. As the injury may be mediated by oxidative stress, it could be ameliorated by antioxidants. METHODS: We conducted a double-blind trial, giving the patients a single dose of natural beta-carotene or placebo, 12 hours prior to procedure, and monitoring them for 24 hours post-procedure for procedure complications, antioxidant levels, and plasma oxidation. RESULTS: The overall incidence of acute pancreatitis according to our definition was 9.6%. The incidence of pancreatitis was not significantly different between the beta-carotene group (10%) and the placebo group (9.4%). Four patients in the placebo group had severe pancreatitis (2.22%), but none in the beta-carotene group. This difference is statistically significant. CONCLUSION: We did not see a reduction in the incidence of post-ERCP pancreatitis, but there may be some protective effect of treatment with beta-carotene regarding the severity of disease.

Reduction of exercise-induced asthma oxidative stress by lycopene, a natural antioxidant.

BACKGROUND: Lycopene has previously been shown to have high antioxidative activity. In view of the controversy regarding the beneficial effect of antioxidants on asthma, the acute effects of lycopene (LYC-O-MATO) on airway hyperreactivity were assessed in patients with exercise-induced asthma (EIA). METHODS: Twenty patients with EIA participated in our study to verify the antioxidative effects. The test was based on the following sequence: measurement of baseline pulmonary function, 7-min exercise session on a motorized treadmill, 8-min rest and again measurement of pulmonary function, 1-week, oral, randomly administered, double-blind supplementation of placebo or 30 mg/day of lycopene (LYC-O-MATO), measurement of pulmonary function at rest, 7-min exercise session, and 8-min rest and again measurement of pulmonary function. A 4-week washout interval was allowed between each protocol. RESULTS: All patients given placebo showed significant postexercise reduction of more than 15% in their forced expiratory volume in 1 s (FEV1). After receiving a daily dose of 30 mg of lycopene for 1 week, 11 (55%) patients were significantly protected against EIA. Serum analyses of the patients by high-pressure liquid chromatography detected in the lycopene-supplemented patients an elevated level of lycopene compared to the placebo group, with no change in retinol, tocopherols, or in the other carotenoids. CONCLUSIONS: Our results indicate that a daily dose of lycopene exerts a protective effect against EIA in some patients, most probably through an in vivo antioxidative effect.

Dietary supplementation of a natural isomer mixture of beta-carotene inhibits oxidation of LDL derived from patients with diabetes mellitus.

BACKGROUND: Accelerated atherosclerosis is common in patients with diabetes mellitus which may be linked to increased lipid peroxidation. Therefore, we compared the oxidation of LDL derived from patients with diabetes to normoglycemic controls and followed-up the effect of dietary beta-carotene supplementation on LDL oxidation. METHODS: Twenty patients with long-standing non-insulin-dependent diabetes mellitus were studied in comparison with age- and sex-matched control subjects. Dunaliella bardawil-derived beta-carotene was supplemented to the patients for 3 weeks, 60 mg daily dose. LDL oxidation was analyzed by measuring malondialdehyde (MDA), lipid peroxides (PD), and conjugated dienes (CD) generation in response to CuSO(4)-induced oxidation. LDL lipid composition and the LDL associated vitamins A, E and carotenoids were also measured. RESULTS: LDL susceptibility to oxidation by CuSO(4) was increased in the patients by 40% with a 35% shorter lag time required for the initiation of LDL oxidation, i.e. 56 +/- 6 min in patients vs. 85 +/- 9 min in controls (p <0.01). Patients showed increased cholesterol/phospholipid and polyunsaturated/saturated ratios, as well as reduced content of LDL associated vitamins. Upon beta-carotene supplementation, there was a significant elevation in plasma and in LDL all-trans beta-carotene [from 0.296 +/- 0.020 to 0. 968 +/- 0.133 microg/mg LDL protein (p < 0.01)] paralleled by a significant reduction in LDL susceptibility to oxidation, as exhibited by increased lag time up to 115 +/- 10 min (p < 0.01) and reduction in MDA and PD generation (by 25 and 40%), respectively (p < 0.01). CONCLUSIONS: Increased susceptibility to oxidation of LDL derived from patients with diabetes mellitus is associated with abnormal LDL lipid composition and antioxidant content. Natural beta-carotene dietary supplementation normalizes the enhanced LDL oxidation and consequently may be of importance in delaying accelerated development of atherosclerosis in these patients.

Prevention of exercise-induced asthma by a natural isomer mixture of beta-carotene.

BACKGROUND: The unicellular alga Dunaliella bardawil was previously shown to contain very high concentrations of beta-carotene composed of equal amounts of the all-trans and 9-cis stereoisomers which differ in their physicochemical features and antioxidative activity. Due to the controversy regarding the beneficial effect of antioxidants on asthma, the acute effects of beta-carotene of Dunaliella was assessed on airway hyperreactivity in patients with exercise-induced asthma (EIA). METHODS: Thirty-eight patients with EIA participated in our study to verify the antioxidative effect. The test was based on the following sequence: baseline pulmonary function, 7 minutes exercise session on a motorized treadmill, 8 minutes rest, 1-week oral random, double-blind supplementation of placebo or 64 mg/day beta-carotene, pulmonary functions at rest, 7 minutes exercise session, 8 minutes rest and again pulmonary functions. RESULTS: All patients given placebo showed a significant postexercise reduction of more than 15% in their forced expiratory volume in one second (FEV1). Of the 38 patients who received a daily dose of 64 mg of beta-carotene for 1 week, 20 (53%) were protected against EIA. CONCLUSIONS: Our results indicate that a daily dose of Dunaliella beta-carotene exerts a protective effect against EIA in some patients most probably through in vivo antioxidative effect.

Availability and antiperoxidative effects of beta-carotene from Dunaliella bardawil in alcohol-drinking rats.

The present study demonstrated the high bioavailability and antiperoxidative capacity of the natural beta-carotene isomer mixture of Dunaliella bardawil compared with synthetic beta-carotene under alcohol-induced oxidative stress. Weanling rats were adapted to ethanol by increasing ethanol levels in their drinking water to 30% at 5% intervals per week; other rats received water with no added ethanol. One water-drinking group and one alcohol-drinking group with no dietary carotene were used as controls. Two water-drinking groups were supplemented with 1 g/kg diet beta-carotene either from Dunaliella or a synthetic source, and due to reduced food intake, two ethanol-fed groups received 2 g beta-carotene per kilogram of diet from each source. Following 3 months of ethanol consumption, both carotene sources were found to prevent ethanol-induced lipid peroxidation as expressed by the hepatic conjugated oxidized dienes level. However, in the algal-fed rats, hepatic carotene and vitamin A levels were higher. In addition to a lower performance of the group fed ethanol and synthetic beta-carotene, there were three deaths in this group.

Effect of natural beta-carotene supplementation in children exposed to radiation from the Chernobyl accident.

Attempts were made to evaluate 709 children (324 boys and 385 girls) who had been exposed long-term to different doses of radiation during and after the Chernobyl accident and had moved to Israel between 1990 and 1994. Upon arrival, all of them underwent a check-up for most common clinical disorders and were then divided into three groups according to their residences (distance from the reactor) and the level of irradiation exposure: no radiation, <5 Ci/m2, and >5 Ci/m2, respectively. Blood serum analyses for total carotenoids, retinol, alpha-tocopherol and oxidized conjugated dienes in 262 of the children showed increased HPLC levels of conjugated dienes, indicating increased levels of oxidation of in vivo blood lipids in children from the contaminated areas. The levels were higher in girls than in boys. Some 57 boys and 42 girls were given a basal diet with a diurnal supplementation of 40 mg natural 9-cis and all-trans equal isomer mixture beta-carotene in a capsulated powder form of the alga Dunaliella bardawil, for a period of 3 months. Blood serum analyses were regularly conducted before supplementation to determine the baseline effect of radiation exposure to the children, after 1 and 3 months of natural beta-carotene supplementation. After supplementation, the levels of the oxidized conjugated dienes decreased in the children's sera without any significant changes in the level of total carotenoids, retinol or alpha-tocopherol. Other common blood biochemicals were within the normal range for all tests and no statistical differences before or after supplementation of beta-carotene were noted. High pressure liquid chromatography (HPLC) analyses for carotenoids in the blood detected mainly oxycarotenoids, and to a lesser extent, all-trans beta-carotene, alpha-carotene, but not 9-cis beta-carotene. The results suggest that irradiation increases the susceptibility of lipids to oxidation in the Chernobyl children and that natural beta-carotene may act as an in vivo lipophilic antioxidant or radioprotector.

Plasma antioxidants and lipid peroxidation in acute myocardial infarction and thrombolysis.

OBJECTIVES: The aim of this study was to investigate the balance between prooxidative and protective mechanisms in patients with acute myocardial infarction (AMI) throughout streptokinase (STK) therapy. METHODS: Patients who presented to coronary care unit within 3 hours of infarction were followed. Blood was collected before, 2 and 24 hours post STK. Plasma lipid peroxidation was analyzed by a free radical generating system (AAPH) and malondialdehyde equivalents and conjugated dienes quantitated. Plasma vitamins A, E and beta-carotene, were analyzed by HPLC. Patients' results were compared with those from age-matched, healthy control subjects. RESULTS: In 38 patients with AMI, baseline plasma antioxidant vitamin concentration was reduced compared with a healthy control group. Upon STK therapy, there was a significant drop in plasma vitamin E concentration. Successful reperfusion was followed by an increased plasma oxidizability. Plasma lipids were not significantly different in the AMI patients except for a lower HDL-cholesterol concentration. CONCLUSIONS: Patients with AMI showed a drop in plasma antioxidant vitamins. Upon thrombolysis, there was an enhanced lipid peroxidation. These alterations indicate the significance of free radical generation processes in reperfusion injury in AMI patients, and suggest the potential involvement of antioxidants in the management of AMI treated by thrombolysis.

[Effect of an extract containing esterol on plasma cholesterol and oxidants].

16 patients with hypercholesterolemia were treated with an extract of alpha-alpha leaves (esterol) while on a low-fat, low-cholesterol diet. Esterol is believed to inhibit the absorption of cholesterol and bile acids and may interfere with the absorption of essential nutrients. As oxidative modification of lipoproteins is required for the process of atherosclerosis, plasma antioxidant vitamins were followed. After 4 months of treatment, plasma cholesterol decreased by 10% from 282 to 250 mg/dl (p < 0.001) and LDL cholesterol by 13%, from 203 to 177 mg/dl (p < 0.001). Plasma antioxidant vitamins E, A and beta-carotene were unchanged. Thus, esterol has a cholesterol-lowering effect but apparently does not lower fat-soluble, plasma antioxidant vitamins. Both cholesterol-lowering and plasma antioxidant vitamins are important for the primary prevention of coronary artery disease in hypercholesterolemia.

Natural beta-carotene and whole body irradiation in rats.

beta-carotene and other carotenoids are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Whole-body irradiation is known to cause an immunosuppression effect in mammals through the possible initiation and production of reactive oxygen species. We decided to test the possible antioxidative effect against whole-body irradiation of a natural beta-carotene, composed of equal amounts of the all-trans and 9-cis isomers, obtained from the unicellular alga Dunaliella bardawil. Rats were fed on ground commercial food enriched with natural beta-carotene (50 mg/kg diet). On completion of 1 week with beta-carotene, the rats were exposed to a single dose of 4 Gy whole-body irradiation, after which their livers and blood were removed for beta-carotene and retinol analysis in comparison with control livers of animals irradiated or not, or supplemented with beta-carotene after irradiation. A normal increase in body weight with no ill effects was noted in the groups of rats whose diet was supplemented by beta-carotene before and after irradiation, compared with the reduction in the specific growth rate in the group of rats irradiated without beta-carotene. Liver beta-carotene and retinol decreased significantly after irradiation compared with the rats which were not irradiated. This decrease was not shown in rats fed beta-carotene prior to irradiation, and the effect of irradiation was partially cured by supplementation with beta-carotene after irradiation. High-pressure liquid chromatography (HPLC) analysis of the irradiated animals showed a selective decline in 9-cis beta-carotene and in retinol over all-trans beta-carotene and retinyl-esters. These results suggest that 9-cis beta-carotene and retinol protect in vivo against the cellular damage by free radicals induced after whole-body irradiation.

Effect of dietary supplementation of beta-carotene on human monocyte-macrophage-mediated oxidation of low density lipoprotein.

Oxidative modification of low density lipoprotein (LDL), a key step in early atherosclerosis, is protected by the lipoprotein-associated antioxidants. The present study analyzes the effect of beta-carotene in plasma, in LDL and in monocyte-macrophages, on macrophage-mediated oxidation of LDL. We investigated the effect of dietary supplementation of beta-carotene on plasma lipid peroxidation [induced by AAPH (2,2-Azobis-2-amidinopropane hydrochloride)] and on cell-free and cell-mediated oxidation of LDL by human monocyte-derived macrophages (HMDM) in the presence of CuSO4. Significant enrichment with beta-carotene was noted in plasma (twofold), in LDL (2.6-fold) and in HMDM (1.6-fold) 2 weeks after dietary supplementation with 180 mg/day of beta-carotene. Plasma lipid peroxidation analyzed by conjugated dienes generation decreased by 22% (P < 0.01) and LDL susceptibility to oxidation analyzed by malondialdehyde generation decreased by 40% (P < 0.01). After beta-carotene supplementation, beta-carotene-enrichment of HMDM capacity to oxidize native LDL, whereas beta-carotene enrichment of LDL significantly reduced LDL oxidation. In conclusion, then, our results suggest that beta-carotene content of LDL, but not that of the macrophages, is responsible for the inhibition of oxidation of LDL.

Bioavailability of a natural isomer mixture compared with synthetic all-trans beta-carotene in human serum.

The unicellular alga Dunaliella bardawil was shown previously to contain very high concentrations of beta-carotene composed of about equal amounts of the all-trans and 9-cis isomers, which differ in their physicochemical features and antioxidative activity. The uptake of alpha- and beta-carotenes, oxycarotenoids, and other lipophilic substances from a basal diet supplemented with synthetic beta-carotene or dry D. bardawil power was studied in humans. Subjects were given a basal diet supplemented daily with 40 mg beta-carotene, synthetic or natural, for a relatively short period of 14 d. Serum analyses at the end of this period detected mainly oxycarotenoids, and to a lesser extent all-trans beta-carotene and alpha-carotene, but not 9-cis beta-carotene. Retinol was increased by the all-trans beta-carotene diet. A high amount of oxidized dienic, lipophilic polar products was exhibited in HPLC predominantly in sera from the placebo and synthetic all-trans beta-carotene groups by strong, short ultraviolet absorbance peaks of 232 nm. The preferential serum absorption of all-trans beta-carotene over 9-cis beta-carotene, in parallel with the appearance of a high concentration of oxidized dienic products with supplementation of the basal diet with all-trans beta-carotene compared with the low concentration of serum-oxidized dienic products with supplementation with a natural beta-carotene source, suggests that 9-cis beta-carotene acts as an in vivo lipophilic antioxidant more efficiently than does all-trans beta-carotene.

[Relationship between plasma antioxidants and coronary artery disease].

Plasma concentrations of the antioxidants, vitamin E, beta-carotene and vitamin A were studied. 29 patients in whom at least 70% obstruction of 1 coronary artery was found, and 73 who were normal according to noninvasive tests were compared using multivariable, logistic, regression analysis. The group with coronary disease had significantly lower plasma vitamin E and beta-carotene concentrations as compared with the normal group (means +/- SD: 44.2 +/- 18.3 micrograms/ml vs 50.6 +/- 22.4 and 1.0 +/- 0.5 micrograms/ml vs 1.1, respectively) but plasma vitamin A concentration was not reduced. Decrease in plasma antioxidant vitamin concentrations may be linked to atherogenesis by LDL oxidative modification, which explains the inverse relationship found between the risk of coronary artery disease and plasma antioxidant vitamins.

Beta-carotene and CNS oxygen toxicity in rats.

Beta-carotenes are reported to be potent free radical quenchers, singlet oxygen scavengers, and lipid antioxidants. Oxygen free radicals that are produced in excess during exposure to oxygen at high pressures and overwhelm the body's normal antioxidant defense systems seem to mediate the hyperoxic insult. We decided to test the possible protective effect against central nervous system oxygen toxicity of a natural beta-carotene composed of equal amounts of the all-trans and 9-cis isomers obtained from the unicellular halotolerant alga Dunaliella bardawil. Rats implanted with chronic cortical electrodes for continuous electroencephalogram monitoring were fed on ground commercial food enriched with natural beta-carotene (1 g/kg diet). On completion of 1 wk of the diet, the rats were exposed to 0.5 MPa oxygen and then their livers were removed for beta-carotene and vitamin A analysis. A significant increase was noted in the latent period preceding oxygen seizures in the group of rats in which the diet was supplemented by natural beta-carotene compared with rats given a normal diet (38.5 +/- 3.4 vs. 16.8 +/- 1.8 min; P < 0.05). Further experiments are required to evaluate the potential benefit of supplementing the diet of divers and patients exposed to high pressures of oxygen with the beta-carotene-rich D. bardawil.

Effect of dietary supplementation of red or white wine on human blood chemistry, hematology and coagulation: favorable effect of red wine on plasma high-density lipoprotein.

Twenty healthy males were divided into two groups: 10 subjects were supplemented for 2 weeks with 400 ml of red wine (11% alcohol) per day and the other 10 subjects were given 400 ml of white wine (11% alcohol) per day for a similar period. Blood samples were drawn prior to wine supplementation, after 1 week and at the end of the study. No significant effects were found on plasma concentrations of urea, creatinine, bilirubin, creatine kinase, amylase, blood cell counts, platelet counts and platelet aggregation. Both red- and white-wine supplementation resulted in a transient minor reduction in plasma glucose concentration and in a minor elevation in blood coagulation properties such as prothrombin time and partial thromboplastin time. Red (but not white) wine resulted in an 11 and 26% increment in plasma triglyceride concentrations after 1 and 2 weeks of supplementation, respectively. Plasma cholesterol, as well as very-low- and low-density-lipoprotein levels did not change during the 2 weeks of red- or white-wine supplementation. The most impressive effect of red-wine intake was a significant (p < 0.01) increase in plasma high-density lipoprotein (HDL) cholesterol and in plasma apolipoprotein A-I concentrations by up to 26 and 12%, respectively. These effects were not observed after the intake of white wine. We conclude that the major effect of red-wine supplementation (about 40 g of alcohol per day for a period of 2 weeks) was a significant increase in plasma HDL concentration which may contribute to the reduced risk for cardiovascular diseases observed in red-wine drinkers.

Protective effect of Dunaliella bardawil on water-immersion-induced stress in rats.

The functional activity of a natural isomer mixture as compared with synthetic all-trans beta-carotene in rats was investigated in a rat model produced by water-immersion restraint stress. Five-week-old male rats were fed diets supplemented with synthetic all-trans beta-carotene, dry Dunaliella bardawil, and purified natural beta-carotene from D. bardawil at equivalent levels of beta-carotene. After the rats were fed diets containing up to 0.1% beta-carotene for 2 weeks, they were restrained in a wire cage and immersed in a 23 degree C water bath for 20 h. Liver analyses indicated that rats showed higher accumulations of the algal beta-carotene isomer mixture than of the synthetic all-trans beta-carotene. Dunaliella bardawil and purified natural beta-carotene significantly decreased the gastric mucosal lesions. Synthetic beta-carotene did not decrease the lesions. These results suggest that the gastric cytoprotective effect of beta-carotene depends on the amount of beta-carotene accumulated in the body.

Effects of beta-carotene-rich algae Dunaliella bardawil on the dynamic changes of normal and neoplastic mammary cells and general metabolism in mice.

As a possible step to estimate the mechanism of the inhibitory role of Dunaliella bardawil (Db) in the initial progression of spontaneous mammary tumours of SHN virgin mice, the DNA synthesizing enzyme activities and the in vivo 31P-NMR spectroscopy of normal and neoplastic mammary cells were examined in mice fed Db. The blood levels of glucose and free fatty acids and 1H-NMR spectroscopy of serum or urine were also studied in these animals to check the general metabolic background. Beginning at 4 months of age, the experimental and the control mice were given a vitamin A deficient AIN-76TM diet supplemented with Db (the concentration of beta-carotene was 5.1 x 10(-5)%) and AIN-76TM diet containing retinyl palmitate (2.2 x 10(-4)%), respectively, until 3 weeks after mammary tumour appearance (tumourous) or 9 months of age (non-tumourous). An increasing rate of thymidine kinase activity in mammary tumour was decreased by Db, while the thymidylate synthetase activity was affected little by the treatment. Lipid synthesis was accelerated by Db in normal mammary cells; however, no difference was observed between the experimental and the control groups in energy and lipid metabolism of mammary tumour cells. The growth of preneoplastic mammary hyperplastic alveolar nodules was also enhanced by Db. Db prevented an increase of blood levels of glucose and free fatty acids and a decrease of cholin plus phosphorylcholin level after tumour appearance. Liver weights of mice given Db were greater than those of the control in both the tumourous and non-tumourous groups. Db had little effect on the urinary component levels before and after the appearance of mammary tumours. These results indicate that Db promotes the growth of normal mammary gland cells, but inhibits that of neoplastic cells, and that the inhibitory effect of Db on mammary tumour progression is due to its normalizing both the organ specific and the general metabolism.

Preferential inhibition of LDL oxidation by the all-trans isomer of beta-carotene in comparison with 9-cis beta-carotene.

The synthetic all-trans isomer of beta-carotene was recently shown to possess antioxidant properties towards the formation of oxidized low density lipoprotein. In the present study, the binding of the all-trans and the 9-cis isomers of beta-carotene to plasma lipoproteins was investigated, and the effect of these isomers on the susceptibility of plasma lipoprotein to lipid peroxidation and on macrophage uptake of oxidized LDL were studied. Both the synthetic all-trans isomer of beta-carotene and the natural beta-carotene from the algae Dunaliella Bardawil [which is composed of the all-trans (70%) and the 9-cis (30%) isomers], were found to bind similarly to all plasma lipoproteins, following the incubation of beta-carotene with purified lipoproteins or with whole plasma. Incubation of the beta-carotene isomers with whole plasma, followed by separation of the lipoproteins, revealed substantial carotene binding to very low density lipoprotein (VLDL) and to LDL and limited binding to high density lipoprotein (HDL). Lipid peroxidation of VLDL and LDL were significantly inhibited by beta-carotene. The synthetic beta-carotene, however, was twice as effective as the Dunaliella beta-carotene in inhibiting LDL lipid peroxidation (following LDL incubation with copper ions). Cellular degradation of oxidized lipoproteins (mediated via the scavenger receptor) was decreased by 40% and 18%, respectively, when they were prepared by incubation in the presence of synthetic or natural beta-carotene; the control oxidized LDL was prepared in the absence of beta-carotene.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased susceptibility to undergo lipid peroxidation of chylomicrons and low-density lipoprotein in celiac disease.

Gastrointestinal injury involves oxidative damage as the result of oxygen-derived free radicals which are formed during the inflammatory reactions. Chylomicrons which are synthesized by the intestine can thus be exposed to lipid peroxidation in celiac disease. Similarly, low-density lipoprotein (LDL) propensity to oxidation may be enhanced as a result of a direct or indirect effect of the oxidative process. To resolve these possibilities, plasma chylomicrons and LDL were isolated from a patient with celiac disease and from a control healthy subject before and 3 h after a fat-rich meal, and their propensity to copper-induced lipid peroxidation was then analyzed. The patient's chylomicrons, its LDL that was obtained before the fat-rich meal and its LDL that was obtained after the meal demonstrated 220, 39 and 48% elevation in their content of thiobarbituric-acid-reactive substances in comparison with the control lipoproteins. After a complete recovery of the patient's intestine, the susceptibility of the patient lipoproteins to in vitro oxidation returned toward normal levels. In the patient LDL fraction (obtained either before or after the fat-rich meal), but not in the patient's chylomicrons, the carotenoid content was reduced by 70%, vitamin E by 45%, and the LDL content of arachidonic acid was increased by 70% in comparison with the control lipoproteins. On recovery of the patient and return of the intestine to its normal morphology, normalization of all of these constituents was achieved.

Enhanced in vitro oxidation of plasma lipoproteins derived from hypercholesterolemic patients.

In vitro oxidation of plasma lipoproteins, derived from either normolipidemic or hypercholesterolemic subjects, was performed in the presence of copper ions. Following this procedure, hypercholesterolemic low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) demonstrated greater propensity for oxidation than the corresponding normocholesterolemic lipoproteins. The oxidation was determined by the concentration of thiobarbituric acid-reactive substances (TBARS), which was 44%, 71%, and 54% greater in the patients' VLDL, LDL, and HDL in comparison to the normocholesterolemic lipoproteins, respectively. An associated reduction in trinitrobenzensulfonic acid (TNBS) reactivity in the patients' lipoproteins was noted. These changes were consistent whether expressed per lipoprotein protein or per concentration. Macrophage cholesterol esterification induced by oxidized LDL was substantially increased (up to 59%) when patients' lipoproteins were used, in comparison to control lipoproteins. A positive correlation was present between the LDL cholesterol to protein ratio, the extent of lipoprotein oxidation, and macrophage uptake of the oxidized lipoproteins. The lipoprotein content of pro-oxidant and antioxidant constituents was also analyzed. No measurable ferric or copper ions could be found in association with any of the lipoproteins. However, arachidonic acid content of the patients' LDL was 10.1% +/- 1.0% in comparison to 6.2% +/- 0.8% of total lipoprotein fatty acids in the control group (n = 5). Antioxidants such as vitamin E and carotenoids were significantly reduced in all patients' lipoproteins compared with those of controls. Thus, we suggest that increased cholesterol and arachidonic acid content and reduced concentration of antioxidants in lipoproteins of hypercholesterolemic patients may be responsible for the enhanced propensity for oxidation observed in these lipoproteins.