13-hydroxy- and 13-oxooctadecadienoic acids: novel substrates for human UDP-glucuronosyltransferases.
(73/1038)
Although there are numerous studies of glucuronidation of endogenous compounds, information on the glucuronidation of fatty acids is lacking. In the present studies, both linoleic acid (LA) and its biologically active oxidized derivatives, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-oxooctadecadienoic acid (13-OXO), have been shown to be effective substrates for human liver UDP-glucuronosyltransferases (UGT) and recombinant UGT2B7. LA (carboxyl glucuronide) and 13-OXO (carboxyl glucuronide, unproven) were actively glucuronidated by human liver microsomes (HLM) and human recombinant UGT2B7 with similar activities, in the range of 2 nmol/mg. min. The hydroxyl derivative of LA, 13-HODE, was glucuronidated at both the hydroxyl and carboxyl functions with carboxyl glucuronidation predominating (ratio of COOH/OH, 2:1). For all substrates, the K(m) for formation of the carboxyl-linked glucuronide was in the range of 100 to 200 microM while that for the hydroxyl-linked glucuronide was somewhat lower (>100 microM). This is the first demonstration of glucuronidation of LA and its oxidized derivatives, 13-HODE and 13-OXO, by HLM and recombinant UGT2B7. (+info)
Dietary levels of vitamin E and polyunsaturated fatty acids and plasma vitamin E.
(74/1038)
Seventeen daily diets (breakfast, lunch, and dinner) were analyzed from a 35-day menu cycle fed to students, under contract in the University dining halls. This 35-day menu cycle was repeated 6.6 times over the course of two 15-week semesters and registration and final examination periods. The average 2, 500 kcal diet collected during the sixth and seventh menu cycles contained 96 plus or minus 26 g fat of which 19.5 plus or minus 1.8% was linoleate and 28.7 plus or minus 14.2 mg total tocopherol of which 7.5 plus or minus 3.5 mg was RRR-alpha-tocopherol. Blood samples obtained from 26 female undergraduate student volunteers contained adequate levels of plasma total vitamin E, 1.09 plus or minus 0.25 mg/100 ml, despite the observation that 71% and 65% of the diets analyzed did not meet the value tabluated in the eighth edition of "Recommended Dietary Allowances" for adult females in terms of RRR-alpha-tocopherol or total vitamin E activity, respectively. These data emphasize the importance of the average long-term consumption of this fat-soluble vitamin rather than daily intake. (+info)
Recommended dietary allowance for vitamin E: relation to dietary, erythrocyte and adipose tissue linoleate.
(75/1038)
The general trend toward increased consumption of polyunsaturated fatty acids is apparent in the linoleate level of adipose tissue (13.0 plus or minus 1.3%) and erythrocyte lipids (14.0 plus or minus 1.9%) in the present group of female undergraduate student volunteers compared to values reported in the early 1960's. On the basis of the level of linoleate in their diets (19.5 plus or minus 0.8%), it is also apparent that further increases in tissue lipid linoleate levels are to be anticipated, which in turn will result in an increased requirement for vitamin E. It is suggested that adipose tissue linoleate levels in the general population be used as a baseline for the periodic evaluation and revision of the recommended dietary allowance for vitamin E. The recommended dietary allowance could then be phrased in terms of the quantity of vitamin E activity to be consumed per gram linoleate in 100 g adipose tissue fatty acids. A recommendation of 0.6 IU vitamin E activity/g linoleate in 100 g adipose tissue fatty acids is tentatively suggested. (+info)
Titrating dietary linoleate to in vivo platelet function in man.
(76/1038)
Platelet aggregation time significantly increased within 48 hours in response to an increase in dietary linoleate of 4% of calories while disaggregation time decreased significantly in 96 hours. A change as small as 0.5% of calories was associated with significant alterations within 4 days. In this group, dietary linoleate appears to be related to platelet function by the equations Aggregation time equals 41.14 plus 2.79 linoleate Disaggregation time equals 11.04 minus 25.52 linoleate. (+info)
Aldehydic lipid peroxidation products derived from linoleic acid.
(77/1038)
Lipid peroxidation (LPO) processes observed in diseases connected with inflammation involve mainly linoleic acid. Its primary LPO products, 9-hydroperoxy-10,12-octadecadienoic acid (9-HPODE) and 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE), decompose in multistep degradation reactions. These reactions were investigated in model studies: decomposition of either 9-HPODE or 13-HPODE by Fe(2+) catalyzed air oxidation generates (with the exception of corresponding hydroxy and oxo derivatives) identical products in often nearly equal amounts, pointing to a common intermediate. Pairs of carbonyl compounds were recognized by reacting the oxidation mixtures with pentafluorobenzylhydroxylamine. Even if a pure lipid hydroperoxide is subjected to decomposition a great variety of products is generated, since primary products suffer further transformations. Therefore pure primarily decomposition products of HPODEs were exposed to stirring in air with or without addition of iron ions. Thus we observed that primary products containing the structural element R-CH=CH-CH=CH-CH=O add water and then they are cleaved by retroaldol reactions. 2,4-Decadienal is degraded in the absence of iron ions to 2-butenal, hexanal and 5-oxodecanal. Small amounts of buten-1,4-dial were also detected. Addition of m-chloroperbenzoic acid transforms 2,4-decadienal to 4-hydroxy-2-nonenal. 4,5-Epoxy-2-decenal, synthetically available by treatment of 2,4-decadienal with dimethyldioxirane, is hydrolyzed to 4,5-dihydroxy-2-decenal. (+info)
Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression.
(78/1038)
Conjugated linoleic acid (CLA) isomers have a number of beneficial health effects, as shown in biomedical studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferator-activated receptor (PPAR)-gamma response elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and expression of genes important in glucose and lipid metabolism. ZDF rats were fed either a control diet (CON), one of two CLA supplemented diets (1.5% CLA) containing differing isoforms of CLA (47% c9,t11; 47.9% c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50. The 50:50 diet reduced adiposity and improved glucose tolerance compared with all other ZDF treatments. Insulin-stimulated glucose transport and glycogen synthase activity in skeletal muscle were improved with 50:50 compared with all other treatments. Neither phosphatidlyinositol 3-kinase activity nor Akt activity in muscle was affected by treatment. Uncoupling protein 2 in muscle and adipose tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-gamma mRNA was downregulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the improved glucose tolerance in 50:50 rats is attributable to, at least in part, improved insulin action in muscle, and CLA effects cannot be explained simply by reduced food intake. (+info)
Fatty acids and epithelial permeability: effect of conjugated linoleic acid in Caco-2 cells.
(79/1038)
Conjugated linoleic acid (CLA) is a collective term referring to the positional and geometric isomers of linoleic acid. This novel fatty acid has been shown to have a number of beneficial actions, including immunomodulatory, anticarcinogenic, and antiatherogenic effects. Tight junctions of epithelial cells determine epithelial membrane integrity and selective paracellular permeability to ions and macromolecules. Occludin and ZO-1 are integral structural components of the tight junction, which are involved in the biogenesis and functional integrity of the epithelial monolayer. This study investigated the effects of two isomers of CLA (cis-9 and trans-10 isomers) on Caco-2 cell transepithelial resistance (TER) development, paracellular epithelial permeability, and occludin and ZO-1 expression. Caco-2 cells were grown in media supplemented with 0.05 mM linoleic acid, cis-9 CLA, or trans-10 CLA for 21 days. The trans-10 CLA isomer delayed Caco-2 cell TER development, which is an in vitro measure of epithelial cell integrity, and increased paracellular epithelial permeability. Immunofluorescent staining of Caco-2 cell epithelial monolayers grown in media supplemented trans-10 CLA showed that the trans-10 CLA isomer altered distribution of occludin and ZO-1. The trans-10 CLA isomer delayed the acquisition of transepithelial resistance and altered the cellular distribution of occludin, which have important implications in relation to epithelial permeability. (+info)
Cytotoxicity of reactive oxygen species and related agents toward undifferentiated and differentiated rat phenochromocytoma PC12 cells.
(80/1038)
The cytotoxicity of reactive oxygen species and related agents toward cultured rat adrenal medullary phenochromocytoma PC12 cells was examined. These species and agents include hydrogen peroxide, linoleic acid hydroperoxide (LOOH), tert-butyl hydroperoxide, paraquat, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN), and a hypoxanthine-xanthine oxidase system. The respective 50% lethal concentrations (LC50) for undifferentiated and differentiated PC12 cells were found to be 275 and 165 microM of hydrogen peroxide, 58.3 and 35.3 microM of LOOH, 536 and 212 microM of tert-butyl hydroperoxide, 42.5 and 26.5 mM of paraquat, 79.5 and 74.5 mM of AAPH, 412 and 300 microM of AMVN, and 37.2 and 16.6mU x ml(-1) xanthine oxidase activity of the hypoxanthine-xanthine oxidase system. These results show that the differentiated cells were more susceptible to these oxidative agents than the undifferentiated cells. The glutathione peroxidase activity level of the undifferentiated cells was 2-3 times higher than the differentiated cells, the catalase activity level also tended to be higher, the superoxide dismutase activity level was higher on a per-protein-quantity basis but lower on a per-cell-number basis, and the total and reduced glutathione concentration levels were considerably higher. The enhanced susceptibility of the differentiated cells may result from decreases in the activity of glutathione peroxidase and the concentration of its substrate, reduced glutathione (GSH). Further, the preincubation of PC12 cells with alpha-tocopherol or L-buthionine-(R,S)-sulfoximine (BSO) lowered or enhanced their cytotoxicities, respectively. (+info)