Summary
Aim
Of the many biological targets of oxidative stress, lipids are the most involved class
of biomolecules. Lipid oxidation gives rise to a number of secondary products. Malondialdehyde
(MDA) is the principal and most studied product of polyunsaturated fatty acid peroxidation.
This aldehyde is a highly toxic molecule and should be considered as more than just
a marker of lipid peroxidation. Its interaction with DNA and proteins has often been
referred to as potentially mutagenic and atherogenic. This review is intended to briefly
describe the physiological origin of MDA, to highlight its toxicity, describe and
comment on the most recent methods of detection and discuss its occurrence and significance
in pathology.
Data synthesis
In vivo origin as well as reactivity and consequent toxicity of MDA are reviewed.
The most recent and improved procedures for the evaluation of MDA in biological fluids
are described and discussed. The evidence of the occurrence of increased MDA levels
in pathology is described.
Conclusions
In the assessment of MDA, the most common methods of detection are insufficiently
sensitive and disturbed by interference coming from related species or overestimation
derived from stressing analysis conditions. Moreover, no recent nutritional or medical
trials report the use of one of the new and more reliable methods, some of which are
undoubtedly accessible to virtually all the laboratories provided with a common HPLC
or a spectrofluorimeter.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Nutrition, Metabolism and Cardiovascular DiseasesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Oxidative stress in cardiovascular disease: myth or fact?.Arch Biochem Biophys. 2003; 420: 217-221
- Mechanisms of aging: an appraisal of the oxidative stress hypothesis.Free Radic Biol Med. 2002; 33: 575-586
- Role of reactive aldehyde in cardiovascular diseases.Free Radic Biol Med. 2000; 28: 1685-1696
- A suggested mechanism for the production of malonaldehyde during the autoxidation of polyunsaturated fatty acids. Nonenzymatic production of prostaglandin endoperoxides during autoxidation.J Org Chem. 1975; 40 (Letter): 3615-3617
- Formation of malonaldehyde from lipid oxidation products.Biochim Biophys Acta. 1983; 754: 264-270
- Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.Free Radic Biol Med. 1991; 11: 81-128
- On the mechanism of prostacyclin and thromboxane A2 biosynthesis.J Biol Chem. 1989; 264: 141-150
- Lipid peroxidation-DNA damage by malondialdehyde.Mutat Res. 1999; 424: 83-95
- Induction of frameshift and base pair substitution mutations by the major DNA adduct of the endogenous carcinogen malondialdehyde.Proc Natl Acad Sci U S A. 2003; 100: 14247-14252
- Malondialdehyde, a product of lipid peroxidation, is mutagenic in human cells.J Biol Chem. 2003; 278: 31426-31433
- Analysis of DNA-protein crosslinking activity of malondialdehyde in vitro.Mutat Res. 1999; 424: 97-106
- ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis. Demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum.Arterioscler Thromb. 1994; 14: 605-616
- The importance of lipid-derived malondialdehyde in diabetes mellitus.Diabetologia. 2000; 43: 550-557
- Specificity of the thiobarbituric acid reaction: its use in studies of lipid peroxidation.Clin Chem. 1988; 34: 2433-2438
- A simple fluorometric assay for lipoperoxide in blood plasma.Biochem Med. 1976; 15: 212-216
- Increased plasma malondialdehyde levels in glomerular disease as determined by a fully validated HPLC method.Nephrol Dial Transplant. 1999; 14: 946-951
- High-performance liquid chromatography-based thiobarbituric acid tests.Methods Enzymol. 1994; 233: 314-318
- Rapid, fluorimetric-liquid chromatographic determination of malondialdehyde in biological samples.J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 775: 121-126
- Rapid fluorimetric method to detect total plasma malondialdehyde with mild derivatization conditions.Clin Chem. 2003; 49: 690-692
- Kinetic behaviour of the malonaldehyde-thiobarbituric acid reaction. kinetic-fluorimetric determination of malonaldehyde in human serum.Anal Chim Acta. 1996; 320: 125-132
- Determination of thiobarbituric acid adduct of malondialdehyde using on-line microdialysis coupled with high-performance liquid chromatography.Anal Sci. 2003; 19: 621-624
- Determination of free malondialdehyde in human serum by high-performance liquid chromatography.Anal Biochem. 2002; 311: 76-79
- Direct method for quantification of free malondialdehyde with high-performance capillary electrophoresis in biological samples.Clin Chem. 1997; 43: 1982-1984
- Improved method for plasma malondialdehyde measurement by high-performance liquid chromatography using methyl malondialdehyde as an internal standard.J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 785: 337-344
- Diaminonaphthalene, a new highly specific reagent for HPLC-UV measurement of total and free malondialdehyde in human plasma or serum.Free Radic Biol Med. 2001; 31: 242-249
- Free and total malondialdehyde assessment in biological matrices by gas chromatography-mass spectrometry: what is needed for an accurate detection.Anal Biochem. 1999; 266: 222-229
- Use of methyl malondialdehyde as an internal standard for malondialdehyde detection: validation by isotope-dilution gas chromatography-mass spectrometry.Clin Chem. 2002; 48: 2266-2269
- Analysis of malondialdehyde in biological matrices by capillary gas chromatography with electron-capture detection and mass spectrometry.Anal Biochem. 2001; 290: 108-115
- Influence of citrate and EDTA anticoagulants on plasma malondialdehyde concentrations estimated by high-performance liquid chromatography.J Chromatogr B Biomed Sci Appl. 2001; 751: 193-197
- Determination of malondialdehyde in breath condensate by high-performance liquid chromatography with fluorescence detection.J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 766: 107-114
- Measurement by reversed-phase high-performance liquid chromatography of malondialdehyde in normal human urine following derivatisation with 2,4-dinitrophenylhydrazine.J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 794: 353-362
- Mass spectrometric analysis of 2-deoxyribonucleoside and 2′-deoxyribonucleotide adducts with aldehydes derived from lipid peroxidation.Rapid Commun Mass Spectrom. 1998; 12: 1665-1672
- Reaction of malondialdehyde-DNA adducts with hydrazines-development of a facile assay for quantification of malondialdehyde equivalents in DNA.Chem Res Toxicol. 2002; 15: 312-318
- Analysis of the malondialdehyde-2′-deoxyguanosine adduct pyrimidopurinone in human leukocyte DNA by gas chromatography/electron capture/negative chemical ionization/mass spectrometry.Chem Res Toxicol. 1997; 10: 181-188
- Mass spectrometric (HPLC/ESI–MS/MS) quantification of pyrimido[1,3-a]purin-10(3H)-one, a guanine adduct formed by reaction of malondialdehyde with DNA.J Pharm Biomed Anal. 1999; 21: 1053-1061
- An improved 32P-postlabeling/high-performance liquid chromatography method for the analysis of the malondialdehye-derived 1, N2-propanodeoxyguanosine DNA adduct in animal and human tissues.Chem Res Toxicol. 1998; 11: 1032-1041
- Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay.Carcinogenesis. 1998; 19: 1919-1924
- Development of a method for determination of the malondialdehyde-deoxyguanosine adduct in urine using liquid chromatography-tandem mass spectrometry.Anal Biochem. 2003; 315: 147-151
- Plasma malondialdehyde (MDA) levels in breast and lung cancer patients.J Clin Pharm Ther. 2001; 26: 141-144
- Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection.Ann Clin Biochem. 1991; 28: 504-508
- Daily variations of plasma malondialdehyde levels in patients with early breast cancer.Cancer Detect Prev. 2003; 27: 122-126
- Differential effects of pharmacological doses of melatonin on malondialdehyde and glutathione levels in young and old rats.Gerontology. 1999; 45: 67-71
- Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients.Clin Chim Acta. 2002; 326: 143-149
- Erythrocyte malondialdehyde release in vitro: a functional measure of vitamin E status.Clin Chim Acta. 1985; 151: 169-176
- Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study.Clin Biochem. 2002; 35: 621-625
- Nitric oxide levels and lipid peroxidation in plasma of patients with gastric cancer.Jpn J Clin Oncol. 2002; 32: 162-166
- Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method.Clin Chim Acta. 1978; 90: 37-43
- Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukemia.Clin Chim Acta. 2003; 338: 143-149
- Erythrocyte membrane lipid peroxidation and glycosylated hemoglobin in diabetes.Diabetes. 1989; 38: 1539-1543
- Relationship between plasma malondialdehyde levels and adenosine deaminase activities in preeclampsia.Clin Chim Acta. 2002; 322: 169-173
- Lipid peroxidation in hyperlipidaemic patients. A study of plasma using an HPLC-based thiobarbituric acid test.Free Radic Res Commun. 1993; 19: 51-57
- Correlation between plasma malondialdehyde and ceruloplasmin activity values in preeclamptic pregnancies.Clin Biochem. 2001; 34: 505-506
- Trace elements and lipid peroxidation abnormalities in patients with chronic renal failure.Nephron. 1991; 57: 10-15
- The changes of trace elements, malondialdehyde levels and superoxide dismutase activities in pregnancy with or without preeclampsia.Clin Biochem. 2002; 35: 393-397
- Oxidative stress status in patients with diabetes mellitus: relationship to diet.Eur J Clin Nutr. 2003; 57: 999-1008
- Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors.Clin Chem. 1997; 43: 1209-1214
- Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications.Free Radic Biol Med. 2003; 34: 1563-1574
- Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage.Clin Chem. 1993; 39: 2522-2526
- Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity.Free Radic Biol Med. 2002; 32: 148-152
- Solid-phase extraction in malondialdehyde analysis.Anal Biochem. 1997; 249: 20-23
- Decreased serum total antioxidant status and erythrocyte-reduced glutathione levels are associated with increased serum malondialdehyde in atherosclerotic patients.Arch Med Res. 2002; 33: 257-260
- Serum malondialdehyde and prevalent cardiovascular disease in hemodialysis.Kidney Int. 1999; 56: 1078-1083
- Comparison of hemostatic factors and serum malondialdehyde as predictive factors for cardiovascular disease in hemodialysis patients.Am J Kidney Dis. 1999; 34: 438-444
- Comparative studies on different methods of malonaldehyde determination.Methods Enzymol. 1984; 105: 299-305
- Erythrocyte glutathione peroxidase activity, plasma malondialdehyde and erythrocyte glutathione levels in hemodialysis and CAPD patients.Clin Biochem. 2002; 35: 269-273
- Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood.Am J Obstet Gynecol. 1979; 135: 372-376
- Oxidative stress in viral and alcoholic hepatitis.Free Radic Biol Med. 2003; 34: 1-10
- Clinical importance of erythrocyte malondialdehyde levels as a marker for cognitive deterioration in patients with dementia of Alzheimer type: a repeated study in 5-year interval.Clin Biochem. 2002; 35: 137-141
- Total antioxidant capacity and malondialdehyde in acute abdominal pain.Am J Emerg Med. 2002; 20: 79-82
- Detection of malondialdehyde DNA adducts in human colorectal mucosa: relationship with diet and the presence of adenomas.Cancer Epidemiol Biomarkers Prev. 2002; 11: 267-273
- Immunohistochemical detection of malondialdehyde-DNA adducts in human oral mucosa cells.Carcinogenesis. 2002; 23: 207-211
- Oxidative stress in malignant melanoma and non-melanoma skin cancer.Br J Dermatol. 2003; 148: 913-922
Article info
Publication history
Accepted:
May 5,
2005
Received in revised form:
May 2,
2005
Received:
July 21,
2004
Identification
Copyright
© 2005 Elsevier B.V. Published by Elsevier Inc. All rights reserved.