<p class="first" id="d7553087e51">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 elevated
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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