Cytotoxic products of lipid peroxidation

Esterbauer, H., Zollner, H. and Schaur, R.J. (1988). Hydroxy-alkenals cytotoxic products of lipid peroxidation. Atlas of Science Biochemistry 1, 311-319. 

IsoK/LG are Some of the Most Higly Cytotoxic Products of Lipid Peroxidation... 

Some of the decomposition products of lipid peroxidation, such as aldehydes, are extremely cytotoxic and it has been shown that these are formed within atherosclerotic... 

Cleavage of the carbon bonds during lipid peroxidation reactions results in the formation of aldehydic products such as cytotoxic alkanals and alkenals, as well as alkanes. The breakdown products of lipid peroxidation, alkanals such... 

It has been well established that fatty acid metabolites of LOX and cytochrome P450 are implicated in essential aspects of cellular signaling, including the induction of apoptosis. The enzymatic and non-enzymatic products of polyunsaturated fatty acids thus control cell growth and apoptosis, and the spontaneous oxidation of polyunsaturated fatty acids gives rise to reactive aldehydes and other products of lipid peroxidation that are potentially cytotoxic and which may also signal apoptosis [102]. 

Many of these end products of lipid peroxidation are themselves cytotoxic and mutagenic, and can go on to cause further damage to the cell, cross-linking proteins and causing DNA lesions by reaction with amino acid residues and DNA bases. 

Studies carried out with complete cells in vivo, cell membranes and other cell fractions point to the selective oxidation of phosphatidylserine (26) to a hydroperoxide (PS-OOH) on oxidative stress caused by toxic agents such as H2O2, t-BuOOH and cumyl hydroperoxide (27). Formation of PS-OOH is observed during apoptosis. These phenomena are important because of the cytotoxic effects of various peroxides used in commercial products coming into direct contact with the human body, as is the case of epidermal keratinocytes in contact with cosmetic formulations" ". The toxic effects of f-BuOOH are associated with vasoconstriction and damage to the vascular smooth muscles ". Global determination methods for primary lipid oxidation products are discussed in Section IV.B. 

The potential consequences of the peroxidation of membrane lipids include loss of polyunsaturated fatty acids, decreased lipid fluidity, altered membrane permeability, effects on membrane-associated enzymes, altered ion transport, release of material from subcellular compartments, and the generation of cytotoxic metabolites of lipid hydroperoxides. The physiological significance of lipid peroxidation products is shown in Table 1. 

Kiyomiya K, Matsushita N, Matsuo S, and Kurebe M. Roles of oxygen radical production and lipid peroxidation in the cytotoxicity of cephaloridine on cultured renal epithelial cells (LLC- PK1). J Vet Med Sci 62 977-981, 2000. 

Selley et al. (1992) have recently employed gas chromatography combined with mass spectrometric detection to determine levels of the cytotoxic monounsaturated aldehyde 4-hydroxy-/7 t-2-nonenal in the blood plasma of healthy human subjects, and patients with rheumatoid and osteoarthritis. Intriguingly, this lipid peroxidation end-product is present at a concentration ofc. lx 10 mol/dm in healthy and osteoarthritic human plasma samples (but significantly elevated in those collected from rheumatoid arthritis patients). Although at least some of this could originate from the oxidative degradation of PUFAs invm, there may be a relationship existing between these levels and the frequency of thermally/... 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

The products formed during lipid peroxidation include unsaturated aldehydes, such as 4-hydroxynonenal. Their quantification is of great interest because of their extremely reactive and cytotoxic properties. This extreme reactivity and metabolic conversion, however, may make them unsuitable as test analytes for in vivo antioxidant activity studies except at high levels of oxidative stress. Furthermore, simple chemical tests such as the TBARS (thiobarbituric acid reactive substances) and LPO-586 (colorimetric... 

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