Determination of lipid hydroperoxides in native low-density lipoprotein by a chemiluminescent flow-injection assay

Cominacini, Luciano; Pastorino, Antonio M.; McCarthy, Alun D.; Campagnola, M.; Garbin, Ulisse; Davoli, A.; Santis, A. De; Cascio, Vincenzo Lo

doi:10.1016/0005-2760(93)90137-x

Cited by 14 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). The curve arising from this calculation is similar to the observed relationship between the 10-year ASCVD Assumptions are as follows: (i) LDL show similar increases in susceptibility of oxidation with aging as VLDLy; (i) variation in LDL age can be approximated by the reciprocal of the fractional catabolic rate of LDL; (iii) initiation of oxidation was related to the number of hydroperoxides in the lipoprotein particles, availability of catalysts, and the amount of antioxidants in the lipoprotein particle (44)(45)(46); (iv) an increase in the rate of initiation-i.e., increase in lipoprotein hydroperoxide content or catalyst concentration-was responsible for the increase in lipoprotein susceptibility with age (42,43); and (v) there was a linear increase in the initiation rate with lipoprotein age. Assumptions for the physical properties of lipoproteins at risk for oxidation were based on data from males and were as follows: (i) the fractional PUFA content is the primary determinant of susceptibility to oxidation, and PUFA compose 20% of total fatty acids in LDL; (i) a-tocopherol is the predominant antioxidant in dialyzed lipoprotein particles, and each particle contains 5-10 antioxidant molecules (42) …”

Section: Resultsmentioning

confidence: 64%

Older plasma lipoproteins are more susceptible to oxidation: a linking mechanism for the lipid and oxidation theories of atherosclerotic cardiovascular disease.

Walzem

Watkins

Frankel

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Increases in plasma cholesterol are associated with progressive increases in the risk of atherosclerotic cardiovascular disease. In humans plasma cholesterol is contained primarily in apolipoprotein B-based low density lipoprotein (LDL) (7). Thus in the "oxidation theory," the properties of oxidatively modified LDL are the basis for their purported role as the atherogenic LDL species in ASCVD. But why should elevation of plasma LDL concentration accelerate its oxidative modification? Investigations of dietary factors that influence plasma LDL-cholesterol, the "lipid theory," show that consumption of saturated fat increases LDL levels, whereas consumption of polyunsaturated fat decreases LDL levels and, concomitantly, disease risk (8)(9)(10)(11)(12)(13)(14). Yet the chemical composition of LDL-containing polyunsaturated fats should render them more susceptible to oxidative damage. The seeming inconsistencies between the findings of these two distinct research areas could be due to the confounding effects of variable lipoprotein age.Currently, lipoprotein age is uncontrolled in studies attempting to relate concentrations of LDL, or their oxidative susceptibility, to the development of ASCVD. Consideration of lipoprotein age is important because it can vary widely. The classical LDL pathway predicts reduced numbers of highaffinity receptors per cell as cellular cholesterol increases (metabolic down-regulation) (15). This prediction is now established, and decreases in cellular receptor numbers increase the time required for removal of a fixed amount of LDL from plasma (4). Thus, in comparison to individuals with normal levels of plasma cholesterol, individuals that are hypercholesterolemic not only possess higher concentrations of LDL but also substantially older LDL.Oxidative damage of LDL is believed to occur primarily in the subendothelial space of the vascular wall (16). During circulation LDL enter and re-emerge from the subendothelial space (17). Increasing the time needed to remove fixed amounts of LDL from circulation creates conditions that favor increases in the number of LDL exposed to the subendothelium and, perhaps, the duration of that exposure. Repeated or prolonged exposure of lipoproteins like LDL to an oxidative environment could increase their susceptibility to oxidation by Abbreviations: ASCVD, atherosclerotic cardiovascular disease; LDL, low density lipoprotein(s); VLDLy, yolk-specific very low density lipoprotein(s); apo, apolipoprotein; PUFA, polyunsaturated fatty acid(s).

show abstract

Section: Resultsmentioning

confidence: 64%

Older plasma lipoproteins are more susceptible to oxidation: a linking mechanism for the lipid and oxidation theories of atherosclerotic cardiovascular disease.

Walzem

Watkins

Frankel

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Recent studies demonstrated that native LDL contains preformed lipid hydroperoxides [40][41][42] and that they were stable in plasma [43]. The increase in lag phase induced by troglitazone administration may, therefore, be due not only to its radical scavenging activity but also to its ability to reduce trace amounts of preformed lipid hydroperoxides in LDL.…”

Section: Discussionmentioning

confidence: 99%

Troglitazone increases the resistance of low density lipoprotein to oxidation in healthy volunteers

Cominacini

Young²,

Capriati³

et al. 1997

Diabetologia

View full text Add to dashboard Cite

Troglitazone, a thiazolidine-2-dione derivative, is a novel oral anti-diabetic drug under development for the treatment of non-insulin-dependent diabetes (NIDDM). It has been reported to enhance insulin sensitivity [1], increase the conversion of glucose to glycogen in rat HepG2 cells [1], reduce hepatic gluconeogenic enzyme activity in rats and mice [2] and to improve metabolic control in NIDDM patients [3,4].There is a much increased risk of coronary artery disease (CAD) in diabetes and around 60 % of the Diabetologia (1997Diabetologia ( ) 40: 1211Diabetologia ( -1218 Troglitazone increases the resistance of low density lipoprotein to oxidation in healthy volunteers Summary The oxidative modification of low density lipoprotein is of importance in atherogenesis. Antioxidant supplementation has been shown, in published work, to increase low density lipoprotein resistance to oxidation in both healthy subjects and diabetic subjects; in animal studies a contemporary reduction in atherogenesis has been demonstrated. Troglitazone is a novel oral antidiabetic drug which has similarities in structure with vitamin E. The present study assessed the effect of troglitazone 400 mg twice daily for 2 weeks on the resistance of low density lipoprotein to oxidation in healthy male subjects. Ten subjects received troglitazone and ten received placebo in a randomised, placebo-controlled, parallel-group design. The lag phase (a measure of the resistance of low density lipoprotein to oxidation) was determined by measurement of fluorescence development during copper-catalysed oxidative modification of low density lipoprotein. The lag phase was increased by 27 % (p < 0.001) at week 1 and by 24 % (p < 0.001) at week 2 in the troglitazone treated group compared with the placebo group. A number of variables known to influence the resistance of low density lipoprotein to oxidation were measured. They included macronutrient consumption, plasma and lipoprotein lipid profile, alpha-tocopherol, beta-carotene levels in low density lipoprotein, low density lipoprotein particle size, mono and polyunsaturated fatty acid content of low density lipoprotein and pre-formed low density lipoprotein hydroperoxide levels in low density lipoprotein. Troglitazone was associated with a significant reduction in the amount of pre-formed low density lipoprotein lipid hydroperoxides. At weeks 1 and 2, the low density lipoprotein hydroperoxide content was 17 % (p < 0.05) and 18 % (p < 0.05) lower in the troglitazone group compared to placebo, respectively. In summary the increase in lag phase duration in the troglitazone group appeared to be due to the compound's activity as an antioxidant and to its ability to reduce the amount of preformed low density lipoprotein lipid hydroperoxides. This antioxidant activity could provide considerable benefit to diabetic patients where atherosclerosis accounts for the majority of total mortality. [Diabetologia (1997) total mortality in diabetes is due to atherosclerosis and subsequent complications [5]. The reasons for th...

show abstract

Chemiluminescence, Analytical Applications

Nakashima

2003

Kirk-Othmer Encyclopedia of Chemical Technology

View full text Add to dashboard Cite

Chemiluminescence (CL) has many advantageous features as a tool of detection in instrumental analysis, including sensitivity, selectivity and simplicity. A CL reaction needs no excitation light source, thus, it is not accompanied with any scattering light. This results in a large signal‐to‐noise (S/N) ratio and consequently, a substantial increase in detector's sensitivity. To date, several kinds of CL reactions have been clarified on their reaction mechanisms. Generally, concentrations of the substrates or catalysts in each CL reaction can be determined by measuring the CL generated. Among the CL reactions, luminol (5‐amino‐2,3‐dihydro‐1,4‐phthalazinedione) derivatives, acridine derivatives, aryloxalate derivatives, and ruthenium derivatives have frequently been utilized in analytical applications. In this article, representative analytical applications of CL in liquid phase for the determination of a variety of compounds are described.

show abstract

Determination of lipid hydroperoxides in native low-density lipoprotein by a chemiluminescent flow-injection assay

Cited by 14 publications

References 38 publications

Older plasma lipoproteins are more susceptible to oxidation: a linking mechanism for the lipid and oxidation theories of atherosclerotic cardiovascular disease.

Older plasma lipoproteins are more susceptible to oxidation: a linking mechanism for the lipid and oxidation theories of atherosclerotic cardiovascular disease.

Troglitazone increases the resistance of low density lipoprotein to oxidation in healthy volunteers

Chemiluminescence, Analytical Applications

Contact Info

Product

Resources

About