scholarly journals GLYCATED LOW-DENSITY LIPOPROTEIN IN DIABETIC AND NON-DIABETIC PATIENTS

Author(s):  
OMAR ABDULWAHID AL-ANI ◽  
ABDURRAHMAN AL-BAZZAZ

Objective: The importance of measuring the blood level of modified low-density lipoprotein (LDL) molecules is an effective method of identifying people at risk of coronary atherosclerosis; this is because, in the early stages of atherosclerosis, lipolysis and oxidative modification have a role in promoting the uptake of these lipids through macrophages; therefore, this research aims to measure the level of glycated LDL (Gly-LDL) in the blood and its association with metabolic parameters of diabetic patients (diabetes mellitus) and non-diabetic (hyperlipidemia). Methods: At a University Diabetes Center in Riyadh, we using routine automatic analysis methods, fasting serum samples were analyzed for 31 patients with Type-2 diabetes and 31 non-diabetic patients for LDL, high-density lipoprotein (HDL), total cholesterol, glycated hemoglobin, glucose, and triglycerides (TG), and using enzyme-linked immunosorbent assay to analyze Gly-LDL for the same sample. Results: The level of serum Gly-LDL in non-diabetic was higher than in diabetic patients (p=0.037). Gly-LDL level correlated significantly with LDL in the diabetic group (p=0.035) and was insignificant with other parameters; moreover, it is significantly correlated with HDL (p=0.048), TG (p=0.035), and very LDL (p=0.03) in the non-diabetic group and insignificant with other parameters. Conclusion: Measuring rates of Gly-LDL can be used in the early detection of cardiovascular disease, especially in people with diabetes, as they are more susceptible to modified and oxidized LDL.

1991 ◽  
Vol 278 (2) ◽  
pp. 429-434 ◽  
Author(s):  
V M Darley-Usmar ◽  
A Severn ◽  
V J O'Leary ◽  
M Rogers

Macrophages derived from the human monocyte cell line THP-1 or isolated from the peritoneum of C3H/HEJ mice were incubated with oxidized low-density lipoprotein (LDL) and the total glutathione content (oxidized plus reduced) was measured. An initial depletion of glutathione was followed by an increase, such that after a period of 24 h the glutathione content has approximately doubled. This response required the oxidation of the lipid phase of the LDL molecule, since both native LDL and acetylated LDL had little effect on glutathione levels. The response of the cells to oxidized LDL was dependent on the extent of oxidative modification of the protein. It was also found that 4-hydroxynonenal had a similar effect on THP-1 cells, and we suggest that this or other aldehydes present in oxidized LDL causes the induction of glutathione synthesis in response to an initial oxidative stress and consequent glutathione depletion. In addition, we found that both cell types possess transferases and peroxidases capable of detoxifying aldehydes and peroxides. However, treatment of cells with oxidized LDL or 4-hydroxynonenal for a period of 24 h had no effect on the activities of these enzymes.


1990 ◽  
Vol 265 (2) ◽  
pp. 605-608 ◽  
Author(s):  
G Jürgens ◽  
A Ashy ◽  
H Esterbauer

4-Hydroxynonenal (HNE) is a major aldehydic propagation product formed during peroxidation of unsaturated fatty acids. The aldehyde was used to modify freshly prepared human low-density lipoprotein (LDL). A polyclonal antiserum was raised in the rabbit and absorbed with freshly prepared LDL. The antiserum did not react with human LDL, but reacted with CuCl2-oxidized LDL and in a dose-dependent manner with LDL, modified with 1, 2 and 3 mM-HNE, in the double-diffusion analysis. LDL treated with 4 mM of hexanal or hepta-2,4-dienal or 4-hydroxyhexenal or malonaldehyde (4 or 20 mM) did not react with the antiserum. However, LDL modified with 4 mM-4-hydroxyoctenal showed a very weak reaction. Lipoprotein (a) and very-low-density lipoprotein were revealed for the first time to undergo oxidative modification initiated by CuCl2. This was evidenced by the generation of lipid hydroperoxides and thiobarbituric acid-reactive substances, as well as by a marked increase in the electrophoretic mobility. After oxidation these two lipoproteins also reacted positively with the antiserum against HNE-modified LDL.


1994 ◽  
Vol 302 (1) ◽  
pp. 297-304 ◽  
Author(s):  
L J Hazell ◽  
J J M van den Berg ◽  
R Stocker

Peroxidation of low-density lipoprotein (LDL) lipid is generally thought to represent the initial step in a series of modification reactions that ultimately transform the protein moiety of the lipoprotein into a form recognized by receptors different from those that bind native LDL. Uptake of LDL via these alternative receptors can lead to the formation of lipid-laden cells, which are typical for the early stages of atherogenesis. We have studied the oxidative modification of LDL by hypochlorite (-OCl), a powerful oxidant produced from H2O2 and chloride via the action of myeloperoxidase which is released from activated neutrophils and monocytes. Exposure of LDL to reagent or enzymically generated -OCl at 4 or 37 degrees C resulted in immediate and preferential oxidation of amino acid residues of apolipoprotein B-100, the single protein associated with LDL. Lysine residues quantitatively represented the major target and, like tryptophan, were oxidized to approximately the same extent with reagent or enzymically generated -OCl. In contrast, LDL lipid oxidation was less favoured than protein oxidation, as judged by the amounts of lipid hydroperoxides, chlorohydrins, cholesterol or fatty acid oxidation products formed. Treatment with -OCl caused aggregation of LDL, as shown by an increased turbidity of the oxidized LDL solution and elution from a size-exclusion h.p.l.c. column of high-molecular-mass LDL complexes. Chemical modification of lysine residues before oxidation with -OCl prevented aggregation, while it enhanced the extent of lipid peroxidation. Treatment of LDL with -OCl also caused the formation of carbonyl groups and release of ammonia; both these modifications were inhibited by lysine-residue modification before oxidation. These results demonstrate that aggregation reactions are dependent on initial lysine oxidation by -OCl, followed by deamination and carbonyl formation, but do not involve lipid (per)oxidation. We propose that the observed -OCl-mediated aggregation of LDL is caused, at least in part, by cross-linking of apoproteins by Schiff-base formation independently of lipid peroxidation.


2019 ◽  
Vol 26 (9) ◽  
pp. 1576-1593 ◽  
Author(s):  
Hiroyuki Itabe ◽  
Rina Kato ◽  
Naoko Sawada ◽  
Takashi Obama ◽  
Matsuo Yamamoto

Oxidatively modified low-density lipoprotein (oxLDL) is known to be involved in various diseases, including cardiovascular diseases. The presence of oxLDL in the human circulatory system and in atherosclerotic lesions has been demonstrated using monoclonal antibodies. Studies have shown the significance of circulating oxLDL in various systemic diseases, including acute myocardial infarction and diabetic mellitus. Several different enzyme-linked immunosorbent assay (ELISA) procedures to measure oxLDL were utilized. Evidence has been accumulating that reveals changes in oxLDL levels under certain pathological conditions. Since oxLDL concentration tends to correlate with low-density lipoprotein (LDL)-cholesterol, the ratio of ox-LDL and LDL rather than oxLDL concentration alone has also been focused. In addition to circulating plasma, LDL and oxLDL are found in gingival crevicular fluid (GCF), where the ratio of oxLDL to LDL in GCF is much higher than in plasma. LDL and oxLDL levels in GCF show an increase in diabetic patients and periodontal patients, suggesting that GCF might be useful in examining systemic conditions. GCF oxLDL increased when the teeth were affected by periodontitis. It is likely that oxLDL levels in plasma and GCF could reflect oxidative stress and transfer efficacy in the circulatory system.


1996 ◽  
Vol 316 (2) ◽  
pp. 377-380 ◽  
Author(s):  
Min YANG ◽  
David S. LEAKE ◽  
Catherine A. RICE-EVANS

The oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis, although little is known as yet about the precise mechanism of oxidation in vivo. The studies presented here demonstrate that, in the absence of cells or transition metals, oxidized LDL can modify native LDL through co-incubation in vitro such as to increase its net negative charge, in a concentration-dependent manner. The interaction is not inhibited by peroxyl radical scavengers or metal chelators, precluding the possibility that the modification of native LDL by oxidized LDL is through an oxidative process. Studies with radioiodinated oxidized LDL showed no transfer of radioactivity to the native LDL, demonstrating that fragmentation of protein and the transfer of some of the fragments does not account for the modified charge on the native LDL particle. The adjacency of native to oxidized LDL in the arterial wall may be a potential mechanism by which the altered recognition properties of the apolipoprotein B-100 may arise rapidly without oxidation or extensive modification of the native LDL lipid itself.


1993 ◽  
Vol 290 (1) ◽  
pp. 165-172 ◽  
Author(s):  
L J Hazell ◽  
R Stocker

Oxidation of low-density lipoprotein (LDL) lipid is thought to represent the initial step in a series of oxidative modification reactions that ultimately transform this lipoprotein into an atherogenic high-uptake form that can cause lipid accumulation in cells. We have studied the effects of hypochlorite, a powerful oxidant released by activated monocytes and neutrophils, on isolated LDL. Exposure of LDL to reagent hypochlorite (NaOCl) at 4 degrees C resulted in immediate and preferential oxidation of amino acid residues of apoprotein B-100, the single protein associated with LDL. Neither lipoprotein lipid nor LDL-associated antioxidants, except ubiquinol-10, represented major targets for this oxidant. Even when high concentrations of NaOCl were used, only low levels of lipid hydroperoxides could be detected with the highly sensitive h.p.l.c. post-column chemiluminescence detection method. Lysine residues of apoprotein B-100 quantitatively represented the major target, scavenging some 68% of the NaOCl added, with tryptophan and cysteine together accounting for an additional 10% of the oxidant. Concomitant with the loss of LDL's amino groups, chloramines were formed and the anionic surface charge of the lipoprotein particle increased, indicated by a 3-4-fold increase in electrophoretic mobility above that of native LDL on agarose gels. While both these changes could be initially reversed by physiological reductants such as ascorbic acid and methionine, incubation of the NaOCl-modified LDL at 37 degrees C resulted in increasing resistance of the modified lysine residues against reductive reversal. Exposure of mouse peritoneal macrophages to NaOCl-oxidized LDL resulted in increased intracellular concentrations of cholesterol and cholesteryl esters. These findings suggest that lipid-soluble antioxidants associated with LDL do not efficiently protect the lipoprotein against oxidative damage mediated by hypochlorite, and that extensive lipid oxidation is not a necessary requirement for oxidative LDL modification that leads to a high-uptake form of the lipoprotein.


2021 ◽  
pp. 801-810
Author(s):  
Hayder Z. Ali ◽  
Harith Saeed Al-Warid

The influence of Toxoplasma gondii on some biochemical parameters has lately gained an increasing attention. The aim of this study was to assess the levels of some biochemical parameters in Toxoplasma positive and negative subjects. An analytical case–control study was achieved in Baghdad for the period from October 2018 until March 2019. Forty nine females participated in this study, with an age range of 18-55 years. The participants were separated into two groups, namely Toxoplasma positive subjects (n=21) and Toxoplasma negative subjects (n=28), based on enzyme-linked immunosorbent assay (ELISA). Blood and serum samples were collected from all subjects to evaluate the serum levels of cholesterol, triglycerides, high density lipoprotein (HDL), very low density lipoprotein (VLDL), low density lipoprotein (LDL), total protein, total globulin and total albumin. The results showed non-significant differences between Toxoplasma positive and negative subjects for all the parameters, although cholesterol levels were lower  (mean 149 mg/dL; range 131.9-165.9 mg/dL) in Toxoplasma positive patients as compared to those in Toxoplasma negative subjects (161 mg/dL; 146.7-175 mg/dL).  In addition, triglycerides levels were lower  (160 mg/dL; 123.3-196.8 mg/dL) in Toxoplasma positive subjects as compared to the control subjects (165mg/dL; 134.2-195.3 mg/dL). The only significant difference was noticed among subjects with an age range of 26-35 years, where globulin level was significantly higher (p=0.023)  in Toxoplasma negative subjects as compared to that in Toxoplasma positive subjects.


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