2-nonenal peroxides

The identification and quantification of potentially cytotoxic carbonyl compounds (e.g. aldehydes such as pentanal, hexanal, traw-2-octenal and 4-hydroxy-/mAW-2-nonenal, and ketones such as propan- and hexan-2-ones) also serves as a useful marker of the oxidative deterioration of PUFAs in isolated biological samples and chemical model systems. One method developed utilizes HPLC coupled with spectrophotometric detection and involves precolumn derivatization of peroxidized PUFA-derived aldehydes and alternative carbonyl compounds with 2,4-DNPH followed by separation of the resulting chromophoric 2,4-dinitrophenylhydrazones on a reversed-phase column and spectrophotometric detection at a wavelength of378 nm. This method has a relatively high level of sensitivity, and has been successfully applied to the analysis of such products in rat hepatocytes and rat liver microsomal suspensions stimulated with carbon tetrachloride or ADP-iron complexes (Poli etui., 1985). 

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/... 

Van der Vtiet, A., Van der Aar, E.M., and Bast, A., 1991, The Upid peroxidation product 4-hydroxy-2,3-trans-l nonenal decreases rat intestinal smooth muscle function in-vitro by alkylation of sulphydryl groups, J. Pharm. Pharmacol. 43 515-517. 

In relation to cancer, there is some evidence that highly oxidized and heated fats may have carcinogenic characteristics. HNE (4-hydroxy-2-frans-nonenal), a secondary lipid peroxidation product derived from linoleic acid oxidation, has assumed particular interest because it has shown cytotoxic and mutagenic properties. Its toxicity, as well other secondary lipid peroxidation products (HHE 4-hydroxy-2-frans-hexenal and HOE 4-h yd roxy-2-trans-oc ten al), is explained through the high reactivity with proteins, nucleic acids, DNA, and RNA. Research links them to different diseases such as atherosclerosis, Alzheimer s, and liver diseases (Seppanen and Csallany, 2006). Research is rapidly progressing, but results are still not conclusive. 

An intermediate in Eq. 21-13 may be converted to 4-hydroxy-2-nonenal, a prominent product of the peroxidation of arachidonic or linoleic acids (Eq. 21-15).242 243a However, other biosynthetic pathways to this compound are possible.244 2443 4-Hydroxy-2-nonenal can react with side chains of lysine, cysteine, and histidine245 to form fluorescent products such as the following cyclic compound generated by an oxidative reaction.246... 

Lu C., Chan S. L., Haughey N., Lee W. T., and Mattson M. P. (2001). Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on V-methyl-D-aspartate channels. J. Neurochem. 78 577-589. 

Figure 13.7. Glutathione conjugation to reactive metabolites by GSTs. Ultimate carcinogens such as benzo[a]pyrene 7,8-diol 9,10-epoxide and aflatoxin B1 8,9-epoxide are glutathione-conjugated for detoxification by GSTM1, GSTp, and GST A, respectively. Lipid peroxidation product 4-hydroxy-2-nonenal is preferentially detoxified by GSTA.

Figure 22.7. The major DNA lesions of the lipid peroxidation products. (A) DNA lesions produced by malondialdehyde. Mi denotes the monomeric form of malondialdehyde. Malo-ndialdehyde can polymerize to form dimers and trimers that can also react with DNA. The resulting lesions are designated as M2 and M3, respectively (c.g., M2G). These lesions, however, may not be significant in cells as polymerization of malondialdehyde is relatively slow at neutral pH. (B) The l,7V2-propano-dG DNA adducts produced by acrolein, crotonaldehyde, and 4-hydroxy-2-nonenal (HNE). Stereochemistry is not shown. The l.A -acrolcin-dG consists of three isomers. The 1, AAcrotonaldchyde-dG consists of two isomers. The FAAlINF-dGconsistsof four isomers. (C)EthenoDNAadductsproduced by 2,3-epoxy-4-hydroxynonenal. Further oxidation of 4-hydroxynonenal produces 2,3-epoxy-4-hydroxynonenal, which reacts with DNA to form the exocyclic etheno adducts.

In a similar biochemically oriented vein, several papers were published during 2003 in the journal Chemical Research in Toxicology, representing yet another area of applicability of 3 mm NMR probe capabilities. In the first of these reports, Hankin et al.159 described the results of an investigation into the covalent binding of leukotriene A4 to DNA and RNA. Later in 2003, Blair and co-workers160 reported on the characterization of 2 -deoxycytidine adducts derived from 4-oxo-2-nonenal, a novel lipid peroxidation product. Two of the adducts characterized, Ai and A2, were consistent with substituted ethano-deoxycytidine structures. The third adduct, B, was characterized as a 7-heptanone-etheno-deoxycytidine adduct (78). 

Perfluoroether monomers 3,5-dioxa-l-heptene, (I), and 3,5,8-trioxa-l-nonene, (II), were prepared by the author [1] and polymerized with tetrafluoroethylene using perfluoropropionyl-peroxide as the reaction initiator. 

Butterfield DA, Reed T, Perluigi M, De Marco C, Cocda R, Cini C, Sultana R (2006b) Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mUd cognitive impairment. Neurosci Lett 397 170-173 Butterfield DA, Stadtman ER (1997) Protein oxidation processes in aging brain. Adv CeU Aging Gerontol vol. 2 pp. 161-191... 

Hyun DH, Lee MH, Halliwell B, Jenner P (2002) Proteasomal dysfunction induced by 4-hydroxy-2,3-trans-nonenal, an end-product of lipid peroxidation a mechanism contributing to neurodegeneration J Neurochem 83 360-370... 

Hamdane M, Delobel P, Sambo AV, Smet C, Begard S, fioUeau A, Landrieu I, Delacourte A, Lippens G, Flament S, Buee L (2003) Neurofibrillary degeneration of the Alzheimer-type tm alternate pathway to neuronal apoptosis Biochem Pharmacol 66 1619-1625 Hayashi T, Shishido N, Nakayama K, Nunomura A, Smith MA, Perry G, Nakamura M (2007) Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-beta peptide. Free Radic Biol Med 43 1552-1559... 

Kuo, C.-L. Vaz, A.D.N. Coon, M.J. Metabolic activation of trans-4-hydroxy-2-nonenal, a toxic product of membrane lipid peroxidation and inhibitor of P450 cytochromes. J. Biol. Chem. 1997, 272, 22,611-22,616. 

Another mechanism of ethanol toxicity involves oxidative stress. Ethanol-induced liver disease is associated with significant oxidative stress as well as with increased levels of iron, which is also known to initiate oxidative stress in the liver. The combined oxidative stress induced by ethanol and iron greatly increases results in lipid peroxidation and the production of aldehydes such as 4-hydroxy-2-nonenal, compounds that have... 

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