Review article
Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury

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Abstract

Increasing appreciation of the causative role of oxidative injury in many disease states places great importance on the reliable assessment of lipid peroxidation. Malondialdehyde (MDA) is one of several low-molecular-weight end products formed via the decomposition of certain primary and secondary lipid peroxidation products. At low pH and elavated temperature, MDA readily participates in nucleophilic addition reaction with 2-thiobarbituric acid (TBA), generating a red, fluorescent 1:2 MDA:TBA adduct. These facts, along with the availability of facile and sensitive methods to quantify MDA (as the free aldehyde or its TBA derivative), have led to the routine use of MDA determination and, particularly, the “TBA test” to detect and quantify lipid peroxidation in a wide array of sample types. However, MDA itself participates in reactions with molecules other than TBA and is a catabolic substrate. Only certain lipid peroxidation products generate MDA (invariably with low yields), and MDA is neither the sole end product of fatty peroxide formation and decomposition nor a substance generated exclusively through lipid peroxidation. Many factors (e.g., stimulus for and conditions of peroxidation) modulate MDA formation from lipid. Additional factors (e.g., TBA-test reagents and constituents) have profound effects on test response to fatty peroxide-derived MDA. The TBA test is intrinsically nonspecific for MDA: nonlipid-related materials as well as fatty peroxide-derived decomposition products other than MDA are TBA positive. These and other considerations from the extensive literature on MDA, TBA reactivity, and oxidative lipid degradation support the conclusion that MDA determination and the TBA test can offer, at best, a narrow and somewhat empirical window on the complex process of lipid peroxidation. The MDA content and/or TBA reactivity of a system provides no information on the precise structures of the “MDA precursor(s),” their molecular origins, or the amount of each formed. Consequently, neither MDA determination nor TBA-test response can generally be regarded as a diagnostic index of the occurrence/extent of lipid peroxidation, fatty hydroperoxide formation, or oxidative injury to tissue lipid without independent chemical evidence of the analyte being measured and its source. In some cases, MDA/TBA reactivity is an indicator of lipid peroxidation; in other situations, no qualitative or quantitative relationship exists among sample MDA content, TBA reactivity, and fatty peroxide tone. Utilization of MDA analysis and/or the TBA test and interpretation of sample MDA content and TBA test response in studies of lipid peroxidation require caution, discretion, and (especially in biological systems) correlative data from other indices of fatty peroxide formation and decomposition.

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    1

    David R. Janero received his B.A. degree summa cum laude with biology honors from Boston University in 1976 and conducted his Ph.D. work at the Yale University School of Medicine in the Department of Cell Biology under Drs. R. Barnett and G.E. Palade. After completing his graduate work, Dr. Janero was appointed a National Institutes of Health Postdoctoral Fellow in the Department of Physiological Chemistry, Johns Hopkins University School of Medicine, under Dr. M.D. Lane's direction. In 1983, he joined Hoffman-La Roche Inc. as a Senior Scientist in the Department of Pharmacology and Chemotherapy and progressed to the rank of Research Investigator. Since 1989, Dr. Janero has been a member of the senior staff, Pharmaceuticals Division, of CIBA-GEIGY Corporation. The efforts of Dr. Janero and his research team are focused on increasing the mechanistic understanding of the pathogenesis of cardiovascular disease and satisfying associated medical needs through the discovery and development of novel therapeutics.

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