Increased levels of lipid oxidation products in low density lipoproteins of patients suffering from rheumatoid arthritis

doi:10.1016/S0009-3084(97)00030-3

Chemistry and Physics of Lipids

Volume 87, Issue 1, 30 May 1997, Pages 81-89

https://doi.org/10.1016/S0009-3084(97)00030-3 Get rights and content

Abstract

9-Hydroxy-10,12-octadecadienoic acid (9-HODE) and 13-hydroxy-9,11-octadecadienoic acid (13-HODE) are accumulated in the low density lipoproteins of patients suffering from rheumatoid arthritis for a factor of 20–50 compared to healthy individuals of the same age. Both acids, derived by lipid peroxidation of linoleic acid, induce the release of interleukin 1β. The latter induces bone degression. The genesis of 9- and 13-HODE seems therefore to be an important factor in the development and progression of rheuma; in addition 9-HODE was reported to be a stimulus of inflammation, comparable to leukotrienes.

Introduction

Lipidperoxidation products of arachidonic acid, e.g. prostaglandines (Bergström and Sjövall, 1957, Bergström et al., 1962), thromboxanes (Hamberg et al., 1975), prostacyclines (Moncada et al., 1976, Moncada et al., 1978) and leukotrienes (Borgeat and Samuelsson, 1979, Murphy et al., 1979, Oerning et al., 1980) are well known potent physiological active compounds in humans and animals. Jasmonic acid, derived by lipid peroxidation of linolenic acid is a comparable potent active compound in plants (Vick and Zimmerman, 1987). In contrast only very little is known about the physiological role of lipid peroxidation products of linoleic acid: Moch et al. (Moch et al., 1990) recognized that 9-Hydroxy-10,12-octadecadienoic (9-HODE), derived by lipid peroxidation of linoleic acid followed by enzymic reduction, has comparable inflammatory potence to leukotrienes. Ku et al. (Ku et al., 1992) reported, that 9-HODE and the isomeric 13-hydroxy-9,11-octadecadienoic acid (13-HODE), but also cholesteryl-9-HODE induce the release of interleukin 1β from macrophages.

Comparing the lipid peroxidation products of myocardial infarcted tissue of a porcine heart with the surrounding non infarcted tissue of the same heart we recognized that the content of 9-HODE was increased for a factor of about 20 (Dudda et al., 1996).

9- and 13-HODE are also main lipid peroxidation products observed after injury of tissue. Hereby hydroxy acids of linoleic acid outweighed those of arachidonic acid for a factor of four, indicating a major involvement of linoleic acid in the LPO process (Herold and Spiteller, 1996). This observation stimulated us to investigate samples of patients suffering from other diseases in which increased amounts of lipid peroxidation products were reported by measurement of thiobarbituric acid reactive substances (TBARS). One of these diseases is rheumatism.

Lunec et al. (Lunec et al., 1981) found increased concentrations of conjugated dienes and fluorescent lipid peroxidation products in the serum and synovial fluid of patients with inflammatory joint diseases. By measuring MDA with the thiobarbituric acid test Muus et al. (Muus et al., 1979) detected, that the MDA concentration in the plasma correlates with disease activity. Selley et al. (Selley et al., 1992) found 4-hydroxy-2-nonenal in plasma and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis. In addition a loss of vitamin E in synovial fluid of rheumatic patients was observed (Fairburn et al., 1993). We report in this paper on the observation of a strong increase of 9- and 13-HODE and enhanced levels of aldehydic compounds in the LDL of patients suffering from RA.

Section snippets

Materials

N-Methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) was obtained from Machery and Nagel (Düren, Germany). All other chemicals were purchased from Fluka (Neu Ulm, Germany). Solvents were destilled before use.

Methods

Blood samples of healthy individuals were obtained from the red cross blood service in Bayreuth. Samples of patients suffering from RA were provided from the hospital in Bayreuth. All patients (with exception of patient no. 8) showed typical signs of RA, considering the revised criteria from

Results

Most of the LOOHs produced during lipid peroxidation (LPO) of LDL are reduced enzymically to their hydroxy derivatives under catalysis by glutathione-dependent peroxidases (Lehmann et al., 1992). Thus determination of LOOHs and LOHs is required to obtain a true picture of the amount of LPO. This is achieved when the total content of LOOHs and LOHs is determined together by reduction of the mixture of hydroperoxides by catalytic hydrogenation (Nikkari et al., 1995), which not only reduces the

Discussion

Reactive oxygen species (ROS) play an important role in the pathology of a wide range of inflammatory diseases (Blake and Lunec, 1990). The involvement of these ROS in the pathogenesis of human rheumatoid diseases is based on the work of McCord (McCord, 1974) who showed that the decreased viscosity of synovial fluid from the joints of patients with RA could also be produced by exposing synovial fluid of hyaluronate (the glycosaminoglycan responsible for most of the synovial fluid viscosity) to

Abbrevations

13-HODE, 13-hydroxy-9,11-octadecadienoic acid; 13-HPODE, 13-hydroperoxy-9,11-octadecadienoic acid; 15-HPETE, 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; 9-HODE, 9-hydroxy-10,12-octadecadienoic acid; 9-LOH, 9-hydroxy octadecanoic acid; 9-LOOH, 9-hydroperoxy octadecanoic acid; AMPA, ammoniummolybdatophosphorus acid; BHT, butylated hydroxytoluene; CH cyclohexane; DMARD, disease-modifying anti-rheumatic drugs; EDTA, ethylene diamine tetra acetic acid; EE, ethylacetate; GC, gas chromatography;

References (47)

J.F. Bilodeau et al.
Effects of nonsteroidal antiinflammatory drugs on oxidative pathways in A/J mice
Free Radical Biol. Med.
(1995)
L.K. Dahle et al.
The thiobarbituric acid reaction and the autoxidation of polyunsaturated fatty acid methyl esters
Arch. Biochem. Biophys.
(1962)
A. Dudda et al.
Lipid oxidation products in ischemic porcine heart tissue
Chem. Phys. Lipids
(1996)
H. Esterbauer et al.
Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal
Methods Enzymol.
(1990)
W.F. Gallwitz et al.
5-Lipoxygenase metabolites of arachidonic acid stimulation isolated osteoclasts to resorb calcified matrices
J. Biol. Chem.
(1993)
M. Herold et al.
Enzymic production of hydroperoxides of unsaturated fatty acids by injury of mammalian cells
Chem. Phys. Lipids
(1996)
D.R. Janero
Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indexes of lipid peroxidation and peroxidative tissue injury
Free Radical Biol. Med.
(1990)
W. Jira et al.
Increase in hydroxy fatty acids in human low density lipoproteins with age
Chem. Phys. Lipids
(1996)
G. Ku et al.
Induction of interleukin 1β expression from human peripheral blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid
J. Biol. Chem.
(1992)
W.A. Lehmann et al.
Profiling assay for lipoxygenase products of linoleic and arachidonic acid by gas chromatography–mass spectrometry
Anal. Biochem.
(1992)

A. Loidl-Stahlhofen et al.

α-Hydroxyaldehydes, products of lipid peroxidation

Biochim. Biophys. Acta

(1994)

A. Mlakar et al.

Previously unknown aldehydic lipid peroxidation compounds of arachidonic acid

Chem. Phys. Lipids

(1996)

P. Muus et al.

Plasma levels of malondialdehyde, a product of cyclo-oxygenase-dependent and independent lipid peroxidation in rheumatoid arthritis: A correlation with disease activity

Prostaglandins Med.

(1979)

J. Nakao et al.

Comparative effect of lipoxygenase products of arachidonic acid on rat aortic smooth muscle cell migration

Atherosclerosis

(1982)

T. Nikkari et al.

Monitoring of lipoprotein oxidation by gas chromatographic analysis of hydroxy fatty acids

J. Lipid Res.

(1995)

H. Rubbo et al.

Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives

J. Biol. Chem.

(1994)

J.C. Sircar et al.

Soybean lipoxygenase inhibition by nonsteroidal antiinflammatory drugs

Prostaglandins

(1983)

F.J.G.M. Van Kuijk et al.

Occurrence of 4-hydroxyalkenals in rat tissues determined as pentafluorobenzyl oxime derivatives by gas chromatography–mass spectrometry

Biochem. Biophys. Res. Commun.

(1986)

F.C. Arnett et al.

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis

Arthritis and rheumatism

(1988)

S. Bergström et al.

The isolation of prostaglandine

Acta Chem. Scand.

(1957)

S. Bergström et al.

The structure of prostaglandin E, F1 and F2

Acta Chem. Scand.

(1962)

Blake, D.R., Lunec, J., 1990. In: Cohen, R.D., Alberti, K.G.M.M., Lewis, B., Denman, A.M. (Eds.), The Metabolic and...

E.C. Bligh et al.

A rapid method of total lipid extraction and purification

Can. J. Biochem. Physiol.

(1959)

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Increased levels of lipid oxidation products in low density lipoproteins of patients suffering from rheumatoid arthritis

Abstract

Introduction

Section snippets

Materials

Methods

Results

Discussion

Abbrevations

Free Radical Biol. Med.

Arch. Biochem. Biophys.

Chem. Phys. Lipids

Methods Enzymol.

J. Biol. Chem.

Chem. Phys. Lipids

Free Radical Biol. Med.

Chem. Phys. Lipids

J. Biol. Chem.

Anal. Biochem.

Biochim. Biophys. Acta

Chem. Phys. Lipids

Prostaglandins Med.

Atherosclerosis

J. Lipid Res.

J. Biol. Chem.

Prostaglandins

Biochem. Biophys. Res. Commun.

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis

Arthritis and rheumatism

The isolation of prostaglandine

Acta Chem. Scand.

The structure of prostaglandin E, F1 and F2

Acta Chem. Scand.

A rapid method of total lipid extraction and purification

Can. J. Biochem. Physiol.