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Mechanisms of lipid peroxidation in human blood plasma: a kinetic approach.
Chem Phys Lipids 1997; 88(2):83-96CP

Abstract

There is strong evidence that the oxidation of plasma lipoproteins plays an important role in atherogenesis. The exact mechanisms by which lipoprotein oxidation occurs in the presence of other plasma constituents, however, remains unclear. To investigate the role of different antioxidants for this process, we studied the oxidation of human plasma supplemented in vitro with physiological amounts of major plasma antioxidants alpha-tocopherol, ubiquinol-10 ascorbate, urate, bilirubin and albumin. The plasma was diluted 2-fold and oxidized by 3.75 mM Cu(II). The concentrations of the antioxidants, fatty acids, linoleic acid hydroperoxides and oxycholesterols in oxidizing plasma were measured. The oxidation was characterized by three consecutive phases similar to the known lag, propagation, and decomposition phases of low density lipoprotein oxidation. The rate of the initiation of oxidation as calculated from antioxidant consumption rates was raised by supplementation with alpha-tocopherol or ascorbate. The oxidation rate in the lag phase was lowered by supplementation with any of the antioxidants, whereas in the propagation phase the oxidation rate was slightly higher in supplemented than in unsupplemented plasma. The kinetic chain length in the lag phase was less than one in supplemented plasma and about one in unsupplemented plasma. The chain length in the propagation phase was between three and six for all plasma samples. A higher rate of urate consumption and a reduced rate of alpha-tocopherol consumption were found in plasma supplemented with ascorbate in comparison with unsupplemented plasma. These data suggest that: (i) the reduction of Cu(II) by alpha-tocopherol and ascorbate is a major initiating event in Cu(II)-catalyzed oxidation of human plasma; (ii) the following lag phase is caused by radical-scavenging effects of all antioxidants with alpha-tocopherol as a major lipophilic and urate as a major hydrophilic scavenger; (iii) interactions between antioxidants, such as regeneration of ascorbate by urate and of alpha-tocopherol by ascorbate, take place during the lag phase; (iv) in the absence of added antioxidants the oxidation in the lag phase can occur via a chain reaction; and (v) in the propagation phase the oxidation is not inhibited by antioxidants and occurs autocatalytically.

Authors+Show Affiliations

Medical Clinic, University of Hamburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9314186

Citation

Karten, B, et al. "Mechanisms of Lipid Peroxidation in Human Blood Plasma: a Kinetic Approach." Chemistry and Physics of Lipids, vol. 88, no. 2, 1997, pp. 83-96.
Karten B, Beisiegel U, Gercken G, et al. Mechanisms of lipid peroxidation in human blood plasma: a kinetic approach. Chem Phys Lipids. 1997;88(2):83-96.
Karten, B., Beisiegel, U., Gercken, G., & Kontush, A. (1997). Mechanisms of lipid peroxidation in human blood plasma: a kinetic approach. Chemistry and Physics of Lipids, 88(2), pp. 83-96.
Karten B, et al. Mechanisms of Lipid Peroxidation in Human Blood Plasma: a Kinetic Approach. Chem Phys Lipids. 1997 Aug 29;88(2):83-96. PubMed PMID: 9314186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of lipid peroxidation in human blood plasma: a kinetic approach. AU - Karten,B, AU - Beisiegel,U, AU - Gercken,G, AU - Kontush,A, PY - 1997/8/29/pubmed PY - 1997/10/6/medline PY - 1997/8/29/entrez SP - 83 EP - 96 JF - Chemistry and physics of lipids JO - Chem. Phys. Lipids VL - 88 IS - 2 N2 - There is strong evidence that the oxidation of plasma lipoproteins plays an important role in atherogenesis. The exact mechanisms by which lipoprotein oxidation occurs in the presence of other plasma constituents, however, remains unclear. To investigate the role of different antioxidants for this process, we studied the oxidation of human plasma supplemented in vitro with physiological amounts of major plasma antioxidants alpha-tocopherol, ubiquinol-10 ascorbate, urate, bilirubin and albumin. The plasma was diluted 2-fold and oxidized by 3.75 mM Cu(II). The concentrations of the antioxidants, fatty acids, linoleic acid hydroperoxides and oxycholesterols in oxidizing plasma were measured. The oxidation was characterized by three consecutive phases similar to the known lag, propagation, and decomposition phases of low density lipoprotein oxidation. The rate of the initiation of oxidation as calculated from antioxidant consumption rates was raised by supplementation with alpha-tocopherol or ascorbate. The oxidation rate in the lag phase was lowered by supplementation with any of the antioxidants, whereas in the propagation phase the oxidation rate was slightly higher in supplemented than in unsupplemented plasma. The kinetic chain length in the lag phase was less than one in supplemented plasma and about one in unsupplemented plasma. The chain length in the propagation phase was between three and six for all plasma samples. A higher rate of urate consumption and a reduced rate of alpha-tocopherol consumption were found in plasma supplemented with ascorbate in comparison with unsupplemented plasma. These data suggest that: (i) the reduction of Cu(II) by alpha-tocopherol and ascorbate is a major initiating event in Cu(II)-catalyzed oxidation of human plasma; (ii) the following lag phase is caused by radical-scavenging effects of all antioxidants with alpha-tocopherol as a major lipophilic and urate as a major hydrophilic scavenger; (iii) interactions between antioxidants, such as regeneration of ascorbate by urate and of alpha-tocopherol by ascorbate, take place during the lag phase; (iv) in the absence of added antioxidants the oxidation in the lag phase can occur via a chain reaction; and (v) in the propagation phase the oxidation is not inhibited by antioxidants and occurs autocatalytically. SN - 0009-3084 UR - https://www.unboundmedicine.com/medline/citation/9314186/Mechanisms_of_lipid_peroxidation_in_human_blood_plasma:_a_kinetic_approach_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-3084(97)00038-8 DB - PRIME DP - Unbound Medicine ER -