Oxidation of alpha 1-protease inhibitor: role of lipid peroxidation products

1989 ◽  
Vol 66 (5) ◽  
pp. 2211-2215 ◽  
Author(s):  
V. Mohsenin ◽  
J. L. Gee

Previously we demonstrated that in vivo exposure of humans to NO2 resulted in significant inactivation of alpha 1-protease inhibitor (alpha 1-PI) in the bronchoalveolar lavage fluid. However, alpha 1-PI retains its elastase inhibitory activity in vitro when exposed to 10 times the concentration of NO2 used in vivo. We suggested exogenous oxidants such as O2 and NO2 exert their effect in vivo in part through lipid peroxidation. We investigated the mechanism of inactivation of alpha 1-PI in the presence or absence of lipids under oxidant atmosphere. alpha 1-PI in solutions containing phosphate buffer (control), 0.1 mM stearic acid (saturated fatty acid, 18:0), or 0.1 mM linoleic acid (polyunsaturated fatty acid, 18:2) was exposed to either N2 or NO2 (50 ppm for 4 h). Elastase inhibitory capacity of alpha 1-PI was significantly diminished in the presence of 0.1 mM linoleic acid and under NO2 atmosphere (75 +/- 8% of control, P less than 0.01), whereas there was no change in elastase inhibitory capacity of alpha 1-PI in the presence or absence (buffer only) of 0.1 mM stearic acid under a similar condition (109 +/- 11 and 94 +/- 6%, respectively). The inactivated alpha 1-PI as the result of peroxidized lipid could be reactivated by dithiothreitol and methionine sulfoxide peptide reductase, suggesting oxidation of methionine residue at the elastase inhibitory site. Furthermore the inhibitory effect of peroxidized lipid on alpha 1-PI could be prevented by glutathione and glutathione peroxidase and to some extent by alpha-tocopherol.

1969 ◽  
Vol 23 (4) ◽  
pp. 869-878 ◽  
Author(s):  
J. H. Moore ◽  
R. C. Noble ◽  
W. Steele ◽  
J. W. Czerkawski

1. Sheep were given intraruminal infusions of maize oil or linoleic acid and samples of contents were taken from the rumen and abomasum at different times after the infusions. Hydrolysis of the maize oil occurred in the rumen with the production of mono- and di-glycerides as intermediates. Linoleic acid derived from the maize oil was hydrogenated to stearic acid. When linoleic acid was infused into the rumen, little or no stearic acid was produced and octadecenoic acid accumulated.2. When linoleic acid or maize oil was incubated with rumen contents in an artificial rumen and samples of the reaction mixtures were taken from the apparatus after various time intervals, the results were similar to those obtained in vivo, except that the hydrolysis of maize oil did not give rise to mono- and di-glycerides.3. These results are discussed in relation to previous findings on the effects of intraruminal infusions of maize oil or linoleic acid on the fatty acid composition of the blood triglycerides of sheep.


2019 ◽  
Author(s):  
Rayudika Aprilia Patindra Purba ◽  
Pramote Paengkoum ◽  
Siwaporn Paengkoum

AbstractThis meta-analysis was conducted to predict and assert a way to discover conjugated linoleic acid (CLA) formation in ruminant-derived products as problem solver of human health issues threated by plant-containing tannins. The objective was to expound, to compare, and to confirm the efficiency of tannins cultivating CLA formation whether using in vitro and/or in vivo study. A database was created using the ruminants with selectively 26 experiments comprising 683 dietary treatments as explained in vitro and in vivo methods that were applied as a statistical SAS 9.4 tool. Basically, increasing level of tannins leaded to an underlying decrease in CLA formation (p<0.001), initially at predicting coefficient determination R2=0.193, R2=0.929, and R2=0.549 for CLA in vitro, in vivo of CLA milk shift, and in vivo of CLA meat precipitation, respectively. In vitro may accurately predict to the in vivo observation. Unfortunately, there were no relationship in vitro towards in vivo observation (R2<0.1). It indicated to be difficult to predict CLA from in vitro to in vivo separately situations. According to all studies, the level of tannin’s utilization for inhibiting biohydrogenation was not exceedingly >50 g/kg DM recommended. Secondly, the in vivo method was more suitable for directly observation that concerned in fatty acid transformation.


1980 ◽  
Vol 191 (2) ◽  
pp. 637-643 ◽  
Author(s):  
William W. Christie ◽  
Margaret L. Hunter

The effects of inclusion of different fatty acids in the medium on the rate of esterification of palmitic acid and its stereospecific distribution among the three positions of the triacyl-sn-glycerols by preparations of rat adipocytes in vitro have been determined. Myristic acid, stearic acid, oleic acid and linoleic acid were used as diluents and the concentration of the combined unesterified fatty acids in the medium was held constant; only the proportion of palmitic acid was varied. The amount of palmitic acid esterified was always linearly related to its relative concentration in the medium and was not significantly affected by the nature of the diluent fatty acid chosen. Constant relative proportions were recovered in triacylglycerols and in intermediates in each instance. The amount of palmitic acid esterified to each of the positions of the triacyl-sn-glycerols was linearly dependent on the relative proportion in the medium but the nature of the relationship was markedly influenced by which fatty acid was present. When stearic acid was present, simple relationships were found over the whole range tested. When either myristic acid, oleic acid or linoleic acid was present, abrupt changes in the manner of esterification of palmitic acid were observed in position sn-1 when the relative concentrations of palmitic acid and the diluent reached critical values, which differed with each fatty acid. In position sn-2 when oleic acid or linoleic acid was present, a similar change was observed, and in position sn-3 it was obtained with myristic acid as diluent. The results are discussed in terms of changes in the relative affinities of the acyltransferases for palmitic acid. Palmitic acid was esterified into various molecular species in proportions that indicated acylation with non-correlative specificity at higher relative concentrations but not at lower.


1981 ◽  
Author(s):  
U M T Houtsmuller ◽  
G Hornstra ◽  
E Haddeman

Arterial thrombus formation is reduced in essential fatty acid (EFA) deficiency. This goes together with an enhanced thrombin induced aggregation of platelets in vitro,whereas collagen-induced aggregation is definitely suppressed. A small amount of linoleic acid (18:2 (n-6)) is able to cure EFA-deficiency and to normalize arterial thrombogenesis. This latter effect may be due to either the structural function of this EFA or to its function as the ultimate dietary precursor of prostaglandins (PG). Columbinic acid, a stereo-isomer of γ-linolenic acid (18:3 (n-6)) was recently shown to possess all the structural functions of EFA, but not the PG-dependent ones. This fatty acid therefore presents a suitable tool to investigate the PG-dependence of arterial thrombogenesis and its underlying processes. We therefore compared the effect of small amounts of linoleic and columbinic acid (both as methylesters) on the water vapour release in vivo (which is a sensitive parameter for a non-PG dependent function of polyenoic fatty acids), arterial thrombosis tendency (time needed for the thrombotic obstruction of an aorta prosthesis) and platelet aggregation in vitro (aggregometry) induced by collagen and thrombin. In contrast to linoleic acid, columbinic acid did not normalize arterial thrombosis tendency and collagen induced platelet aggregation. Columbinic acid was equally effective as linoleic acid in the normalization of the water vapour release in vivo and of the thrombin-induced aggregation. We conclude that arterial thrombus formation and collagen- induced aggregation greatly depend on prostanoid formation, whereas thrombin-induced aggregation does not. The structural role of polyenoic fatty acids in thrombin-induced aggregation may provide a tool in the elucidation of factors determining the thrombin-sensitivity of blood platelets.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Alicja Zajdel ◽  
Adam Wilczok ◽  
Ludmiła Węglarz ◽  
Zofia Dzierżewicz

Phytic acid (PA) has been recognized as a potent antioxidant and inhibitor of iron-catalyzed hydroxyl radical formation underin vitroandin vivoconditions. Therefore, the aim of the present study was to investigate, with the use of HPLC/MS/MS, whether PA is capable of inhibiting linoleic acid autoxidation and Fe(II)/ascorbate-induced peroxidation, as well as Fe(II)/ascorbate-induced lipid peroxidation in human colonic epithelial cells. PA at 100 μM and 500 μM effectively inhibited the decay of linoleic acid, both in the absence and presence of Fe(II)/ascorbate. The observed inhibitory effect of PA on Fe(II)/ascorbate-induced lipid peroxidation was lower (10–20%) compared to that of autoxidation. PA did not change linoleic acid hydroperoxides concentration levels after 24 hours of Fe(II)/ascorbate-induced peroxidation. In the absence of Fe(II)/ascorbate, PA at 100 μM and 500 μM significantly suppressed decomposition of linoleic acid hydroperoxides. Moreover, PA at the tested nontoxic concentrations (100 μM and 500 μM) significantly decreased 4-hydroxyalkenal levels in Caco-2 cells which structurally and functionally resemble the small intestinal epithelium. It is concluded that PA inhibits linoleic acid oxidation and reduces the formation of 4-hydroxyalkenals. Acting as an antioxidant it may help to prevent intestinal diseases induced by oxygen radicals and lipid peroxidation products.


2018 ◽  
Vol 18 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Denis V. Mishchenko ◽  
Margarita E. Neganova ◽  
Elena N. Klimanova ◽  
Tatyana E. Sashenkova ◽  
Sergey G. Klochkov ◽  
...  

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.


Author(s):  
Hassan Ahmadvand ◽  
Majid Tavafi ◽  
Ali Khosrowbeygi ◽  
Gholamreza Shahsavari ◽  
Maryam Hormozi ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2543
Author(s):  
Ruidong Ni ◽  
Suzeeta Bhandari ◽  
Perry R. Mitchell ◽  
Gabriela Suarez ◽  
Neel B. Patel ◽  
...  

Fatty acid amides are a diverse family of underappreciated, biologically occurring lipids. Herein, the methods for the chemical synthesis and subsequent characterization of specific members of the fatty acid amide family are described. The synthetically prepared fatty acid amides and those obtained commercially are used as standards for the characterization and quantification of the fatty acid amides produced by biological systems, a fatty acid amidome. The fatty acid amidomes from mouse N18TG2 cells, sheep choroid plexus cells, Drosophila melanogaster, Bombyx mori, Apis mellifera, and Tribolium castaneum are presented.


Forests ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 285
Author(s):  
Manuela Rodríguez-Romero ◽  
Belén Godoy-Cancho ◽  
Isabel M. Calha ◽  
José António Passarinho ◽  
Ana Cristina Moreira

The ability of three herbaceous plants (Diplotaxis tenuifolia (L.) DC., Eruca vesicaria L. and Raphanus raphanistrum L.) from Iberian wood pastures to reduce Phytophthora cinnamomi Rands pathogen populations through allelopathic relationships is studied. The inhibitory capacity of their aqueous root extracts (AREs) on mycelial growth and production of P. cinnamomi reproductive structures is analysed in vitro. In addition, Quercus seedlings were grown in infested by P. cinnamomi-soils and with the presence or absence of allelopathic and susceptible herb species to the pathogen to assess the defensive chemical response of Quercus seedlings through their leaf phenolic compounds. Results show a strong inhibitory capacity of AREs on P. cinnamomi activity in vitro and a protective effect of these herb species on Quercus plants against P. cinnamomi in vivo. D. tenuifolia would be especially suited for biological control in the pathogen suppression.


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