Aldehydic lipid peroxidation products in human brain astrocytomas

Abstract

Among mediators of oxidative stress, highly reactive secondary aldehydic lipid peroxidation products can initiate the processes of spontaneous mutagenesis and carcinogenesis and can also act as a growth-regulating factors and signaling molecules. We explored whether these aldehydes and histone H3 mRNA levels could serve as biomarkers of malignancy and predictive factor in human brain astrocytomas. Histone H3 mRNA, a biomarker of cellular proliferation, was analyzed by QRT-PCR (TaqMan). Aldehydic lipid peroxidation products were determined as their dinitrophenylhydrazone derivatives in specimens obtained from 26 adult patients with brain astrocytomas. RP-HPLC with diode array detector and MSMS spectrometer were used for the analysis. H3 mRNA, 2-hydroxyhexanal, and 4-hydroxynonenal levels were higher in high-grade astrocytomas compared to low-grade astrocytomas and showed negative correlation with survival. Higher levels of 2-hydroxyhexanal and 4-hydroxynonenal, and lower levels of n-hexanal were associated with poorer patient prognosis. Our data suggest that tissue concentrations of aldehydic lipid peroxidation products can assist grading and predicting the clinical outcome in patients with astrocytic brain tumors. Possibly, this parameter will enhance optimal selection of patients for individualized treatment protocols, tailored to unique biochemical and molecular profile of the tumor.

A carbonyl capture approach for profiling oxidized metabolites in cell extracts

“…The analysis of cellular aldehyde and ketone species is of considerable importance in the field of metabolomics since carbonyl species are pervasive intermediates of normal metabolism as well as common products of oxidative stress (Zajdel et al , 2007); (Noda et al , 2007), which has been implicated in the pathogenesis of many diseases including cancer (Negre-Salvayre et al , 2010). Indeed, the detection and identification of oxidized cellular species, in general, has become an important focus of research efforts in metabolomics where potential early markers of disease are sought (Griffiths et al , 2010; Psychogios et al , 2011); Griffiths et al 2010; (Wikoff et al , 2009).…”

Lipid Peroxidation in Acute Respiratory Distress Syndrome and Liver Failure

“…Because of their ultra-short half time they are more difficult to detect in whole blood, homogenates, or breath [19,20]. Volatile aldehydes have been studied as specific markers of LPO in asthma/chronic obstructive pulmonary disease [21], ARDS [22], in bone marrow after total body X-ray irradiation [23], in diabetes mellitus [24], and diabetic nephropathy [25], malnutrition [26], atherosclerosis [27], stroke patients [13], and most recently in brain tumors [28]. However, no comparative study has been performed yet for different LPO-marker pattern between various organ failures including these volatile aldehydes.…”

Aminooxy reagents in nanomedicine and bioanalysis.

“…The analysis of cellular aldehydes and ketones is of considerable importance in the field of metabolomics since carbonyl species are pervasive intermediates of normal metabolism as well as common products of oxidative stress, [6][7] which has been implicated in the pathogenesis of many diseases including cancer. 8 The detection and identification of oxidized cellular species, in general, has become an important focus of research efforts in metabolomics where potential early markers of disease are sought.…”

“…Such derivatization reagents either have distinct absorbances (for optical detection), preserve or increase volatility (GC), or have easily ionizable groups for MS detection, such as those exemplified in Figure 1.5. 6,[12][13][14][15][16][17] These reagents react with carbonyls via their amine, 12 hydrazine, 14 hydrazide, [18][19][20] or aminooxy [21][22] moieties to form corresponding imine, hydrazone, acyl hydrazone, or oxime ether adducts, respectively. For example, dinitrophenylhydrazine (DNPH) reacts with aldehydes and ketones to form hydrazone derivatives that can be more readily detected due to characteristic UV absorbances.…”

“…For example, dinitrophenylhydrazine (DNPH) reacts with aldehydes and ketones to form hydrazone derivatives that can be more readily detected due to characteristic UV absorbances. 6,14 Similarly, O-2, 3,4,5,6-(pentafluorobenzyl)hydroxylamine (PFBHA) has been used to form stable, and readily ionizable oxime ether derivatives from aldehydes and ketones. [21][22] The silylation of α,β-unsaturated ketones, using a catalyst to facilitate ketone to enol tautomerization and thus enol silylation, also has been performed to improve the GC-MS analysis of this compound class.…”