Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women.
(41/283)
BACKGROUND: Postmenopausal estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL particles. Oral ERT-induced increases in plasma triglyceride, however, decrease LDL particle size, which may counteract this antioxidant effect. Because transdermal ERT decreases plasma triglyceride, it may not decrease LDL particle size and may preserve estrogen's antioxidant effect. The present study investigates whether transdermal ERT can eliminate the adverse effects of oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women. METHODS AND RESULTS: Postmenopausal women received no treatment (n=12) or were treated with either 0.625 mg oral conjugated equine estrogen daily (n=16) or with transdermal estradiol (50 microg/d, n=16) for 3 months. Plasma lipids and the diameter of LDL particles were determined. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO4 and subsequent measurement of thiobarbituric acid reactive substance (TBARS) concentrations. Oral ERT significantly increased plasma triglyceride and decreased LDL diameter but did not affect LDL-derived TBARS concentrations. In contrast, transdermal ERT significantly decreased the concentrations of plasma triglyceride and LDL-derived TBARS and significantly increased LDL diameter. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride (r=-0.51, P<0.001) and LDL-derived TBARS (r=-0.50, P<0.001). CONCLUSIONS: Because transdermal, but not oral ERT, decreases plasma triglyceride and produces larger LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved. (+info)
Oxidized fatty acids promote atherosclerosis only in the presence of dietary cholesterol in low-density lipoprotein receptor knockout mice.
(42/283)
Studies suggest that heated oils contribute to the presence of oxidized components in the circulating lipoproteins and to the development of atherosclerosis in animals. We evaluated the effects of 11-13 wk of consumption of a well defined dietary oxidized fatty acid, 13-hydroxylinoleic acid (13-HODE) (8 mg), on atherosclerotic lesion development and plasma cholesterol concentrations in mice fed diets varying in fat and cholesterol contents. LDL receptor knockout mice were used in two feeding studies. In study 1, oxidized fatty acid consumption in association with a high fat diet increased aortic lesion areas by >100% (P < 0.05). Surprisingly, oxidized fatty acid intake also tended to increase plasma total cholesterol (P = 0.12) and LDL cholesterol (P < 0.05) as well as oxidative stress as measured by higher levels of autoantibodies to oxidatively modified proteins (P = 0.008). However, in mice fed a nonpurified diet, oxidized fatty acids were not atherogenic and may even have been beneficial, as indicated by a lower plasma triglyceride (TG) concentration (P < 0.05). In study 2, mice were fed either a high fat, medium fat or low fat diet to evaluate whether the increase in aortic lesions due to oxidized fatty acid consumption in study 1 was a result of the associated higher plasma total and LDL cholesterol concentrations. In study 2, 13-HODE-treated mice in the medium and low fat diet groups but not those fed the high fat diet had larger atherosclerotic lesions (P < 0.05). Additionally, plasma total and LDL cholesterol as well as TG were not affected by HODE treatment. However, the total cholesterol:HDL cholesterol ratio was higher in treated mice (P < 0.05) and HDL cholesterol was lower in HODE-treated mice that were fed the low fat diet (P < 0.05). Our results suggest that, in mice fed cholesterol, oxidized fatty acids may be atherogenic, both in terms of increased oxidative stress (as seen in study 1) and by increasing the atherogenicity of the plasma cholesterol profile. (+info)
Acquisition of resistance to cisplatin is accompanied by changes in the cellular pharmacology of copper.
(43/283)
Impaired uptake of cisplatin (DDP) consistently accompanies the acquisition of resistance to the platinum drugs. The pathways by which DDP enters or exits from cells remain poorly defined. Using three pairs of human ovarian carcinoma cell lines, each consisting of a sensitive parental line and a stably DDP-resistant subline derived by in vitro selection, resistance to DDP was found to be accompanied by cross-resistance to Cu. Accumulation of DDP in the resistant sublines ranged from 38 to 67% of that in the parental line at 1 h, and DNA adduct formation varied from 10 to 38% of that in the sensitive cells. The DDP-resistant cells had 22-56% lower basal levels of copper, and the copper levels were only 27-46% of those observed in the sensitive parental lines after a 24-h exposure to medium supplemented with copper. The initial influx rate for DDP in the three resistant cell lines ranged from 23 to 55% of that in the sensitive cells of each pair; the initial influx rate for copper in the resistant cells varied from 56 to 75% of control. Studies performed using one pair of cell lines demonstrated that for both copper and DDP the initial efflux rate was lower, whereas the terminal efflux rate was higher in the resistant cells. On Western blot analysis all three resistant lines exhibited increased expression of one or the other of the two copper export pumps (ATP7A or ATP7B) with no change in the HAH1 chaperone. We conclude that the acquisition of DDP resistance in ovarian carcinoma is accompanied by alterations in the cellular pharmacology of DDP that are paralleled by similar changes in the uptake and efflux of copper. These results are consistent with the concept that DDP enters and exits from the cell via transporters that normally mediate copper homeostasis. (+info)
Effect of dietary mannan oligosaccharides and(or) pharmacological additions of copper sulfate on growth performance and immunocompetence of weanling and growing/finishing pigs.
(44/283)
Two experiments were conducted to determine the efficacy of mannan oligosaccharides (MOS) fed at two levels of Cu on growth and feed efficiency of weanling and growing-finishing pigs, as well as the effect on the immunocompetence of weanling pigs. In Exp. 1, 216 barrows (6 kg of BW and 18 d of age) were penned in groups of six (9 pens/treatment). Dietary treatments were arranged as a 2 x 2 factorial consisting of two levels of Cu (basal level or 175 ppm supplemental Cu) with and without MOS (0.2%). Diets were fed from d 0 to 38 after weaning. Blood samples were obtained to determine lymphocyte proliferation in vitro. From d 0 to 10, ADG, ADFI, and gain:feed (G:F) increased when MOS was added to diets containing the basal level of Cu, but decreased when MOS was added to diets containing 175 ppm supplemental Cu (interaction, P < 0.01, P < 0.10, and P < 0.05, respectively). Pigs fed diets containing 175 ppm Cu from d 10 to 24 and d 24 to 38 had greater (P < 0.05) ADG and ADFI than those fed the basal level of Cu regardless of MOS addition. Pigs fed diets containing MOS from d 24 to 38 had greater ADG (P < 0.05) and G:F (P < 0.10) than those fed diets devoid of MOS. Lymphocyte proliferation was not altered by dietary treatment. In Exp. 2, 144 pigs were divided into six pigs/pen (six pens/treatment). Dietary treatments were fed throughout the starter (20 to 32 kg BW), grower (32 to 68 kg BW), and finisher (68 to 106 kg BW) phases. Diets consisted of two levels of Cu (basal level or basal diet + 175 ppm in starter and grower diets and 125 ppm in finisher diets) with and without MOS (0.2% in starter, 0.1% in grower, and 0.05% in finisher). Pigs fed supplemental Cu had greater (P < 0.05) ADG and G:F during the starter and grower phases compared to pigs fed the basal level of Cu. During the finisher phase, ADG increased when pigs were fed MOS in diets containing the basal level of Cu, but decreased when MOS was added to diets supplemented with 125 ppm Cu (interaction, P < 0.05). Results from this study indicate the response of weanling pigs fed MOS in phase 1 varied with level of dietary Cu. However, in phase 2 and phase 3, diets containing either MOS or 175 ppm Cu resulted in improved performance. Pharmacological Cu addition improved gain and efficiency during the starter and grower phases in growing-finishing pigs, while ADG response to the addition of MOS during the finisher phase seems to be dependent upon the level of Cu supplementation. (+info)
Lipoprotein lipase affects the survival and differentiation of neural cells exposed to very low density lipoprotein.
(45/283)
Lipoprotein lipase (LPL) is a key enzyme involved in the metabolism of lipoproteins, providing tissues like adipose tissue or skeletal muscle with fatty acids. LPL is also expressed in the brain, fulfilling yet unknown functions. Using a neuroblastoma cell line transfected with a NEO- or a LPL-expression vector, we have developed a model to study the function of LPL in neurons exposed to native or copper-oxidized lipoproteins. The addition to the culture media of VLDL with 10 microm copper sulfate led to a significant reduction in the viability of NEO transfectants whereas LPL-transfectants were protected from this injury. In the presence of VLDL and CuSO(4), LPL transfectants were even able to display significant neurite extension. This neuritogenic effect was also observed in LPL transfectants exposed to native lipoproteins. However, addition of VLDL particles oxidized with CuSO(4) prior to their addition to the culture media resulted in neurotoxic effects on LPL transfectants. These findings suggest that the presence of LPL in cultured neuronal cells modulates the physiological response of neurons following exposure to native or oxidized lipoproteins. LPL could thus play a key role in the differentiation of Neuro-2A cells and in the pathophysiological effects of oxidative stress in several neurodegenerative disorders. (+info)
Effect of Kohl-Chikni Dawa - a compound ophthalmic formulation of Unani medicine on naphthalene-induced cataracts in rats.
(46/283)
BACKGROUND: Cataracts are the leading cause of blindness worldwide, accounting for 13-27% of cases. Kohl-Chikni Dawa (KCD) is reputed for its beneficial effects in the treatment of premature cataracts. However, its efficacy is yet to be tested. To investigate the rationality of the therapeutic use of Kohl-Chikni Dawa (KCD) in Unani medicine. METHODS: The effect of Kohl-Chikni Dawa eye drops on naphthalene-induced cataracts in rats was investigated by slit-lamp biomicroscopic analysis. The normal group of experimental animals was administered with mineral oil (orally), while other groups were given naphthalene (orally) along with local application of KCD eye drops (once and twice daily), placebo and distilled water (twice daily). Initial morphological changes of the lenses were observed twice a week for two weeks, and thereafter once a week for four weeks. RESULTS: Local application of KCD (twice daily) caused significant reduction in the lens opacification after 2 to 4 weeks of naphthalene administration. CONCLUSION: KCD eye drops may have the potential to delay progression of naphthalene-induced cataracts in rats. (+info)
Effects of breed (Angus vs Simmental) and copper and zinc source on mineral status of steers fed high dietary iron.
(47/283)
Forty-four Angus (n = 24) and Simmental (n = 20) steers, averaging 301 kg initially, were used to determine the effects of breed and Cu and Zn source (SO4 or proteinate (Prot) form) on Cu and Zn status of steers fed high dietary iron (Fe). Steers were stratified by weight within breed and randomly assigned to treatments. Treatments consisted of: 1) CuSO4 + ZnSO4 ,2) CuSO4 + ZnProt, 3) CuProt + ZnSO4, and 4) CuProt + ZnProt. Copper and Zn sources were added to provide 5 mg Cu and 25 mg supplemental Zn/kg DM. All steers were individually fed a corn silage-based diet supplemented with 1,000 mg Fe (from FeSO4)/kg DM. Liver biopsy samples were obtained at the beginning and end of the 149-d study. Serum samples were collected initially and at 28-d intervals for determination of ceruloplasmin activity and Zn and Cu concentrations. Copper and Zn source did not affect performance, serum or liver Cu and Zn concentrations, or ceruloplasmin activity. Copper status decreased (P < 0.01) in all steers with time, and increasing the level of supplemental Cu from 5 to 10 mg/kg DM on d 84 did not prevent further drops in serum Cu and ceruloplasmin. Simmental steers had lower (P < 0.05) serum and liver Cu concentrations, and serum ceruloplasmin activity throughout the study. These results indicate that neither CuSO4 nor CuProt were effective at the supplemental concentrations evaluated in alleviating the adverse effect of high Fe on Cu status. Simmental steers had lower Cu status than Angus, suggesting a higher Cu requirement. (+info)
Effect of alpha-tocopherol on the oxidative modification of apolipoprotein E in human very-low-density lipoprotein.
(48/283)
The oxidative modification of apolipoprotein (apo) E and lipid peroxidation in human very-low-density lipoprotein (VLDL) induced by peroxynitrite and cupric ions in vitro were strongly suppressed by enrichment with alpha-tocopherol (alpha-Toc; 170 microM). Alpha-Toc also suppressed the decrease in the heparin-binding activity of apoE in the VLDL oxidation. These results suggest that alpha-Toc protected apoE in VLDL from oxidative stress. (+info)