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Abstract: In this paper, we provide a systematic analysis of glyoxal (1) formation from a range of monosaccharides and related compounds, to determine their potential role as sources of this α-oxoaldehyde in vivo. Substrates were reacted with the Fenton reagent (Fe2+/EDTA/H2O2) and the mixtures were analyzed by HPLC using the 6-hydroxy-2,4,5-triaminopyrimidine fluorimetric assay. The rank order of hexoses and their derivatives as glyoxal sources was found to be fructose>glucose=mannose=galactose>glucose-6-phosphate>mannitol. Within the pentose group, arabinose and ribose gave the higher yields of 1 followed by deoxyribose and its adenine N-glycosides and ribulose. Among the tested substrates, three-carbon compounds, that is, trioses and glycerol, but not glyceraldehyde-3-phosphate, were by far the most effective sources of 1. The effects of H2O2 and Fe2+/EDTA concentrations as well as of other metal ions were also investigated. [Copyright &y& Elsevier]

Abstract: A comparative evaluation is reported of pro-oxidant states in 82 patients with ataxia telangectasia (AT), Bloom syndrome (BS), Down syndrome (DS), Fanconi anemia (FA), Werner syndrome (WS), and xeroderma pigmentosum (XP) vs 98 control donors. These disorders display cancer proneness, and/or early aging, and/or other clinical features. The measured analytes were: (a) leukocyte and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), (b) blood glutathione (GSSG and GSH), (c) plasma glyoxal (Glx) and methylglyoxal (MGlx), and (d) some plasma antioxidants [uric acid (UA) and ascorbic acid (AA)]. Leukocyte 8-OHdG levels ranked as follows: WS>BS≈FA≈XP>DS≈AT≈controls. Urinary 8-OHdG levels were significantly increased in a total of 22 patients with BS, FA, or XP vs 47 controls. The GSSG:GSH ratio was significantly increased in patients with WS and in young (≤15 years) patients with DS or with FA and decreased in older patients with DS or FA and in AT, BS, and XP patients. The plasma levels of Glx and/or MGlx were significantly increased in patients with WS, FA, and DS. The UA and AA levels were significantly increased in WS and DS patients, but not in AT, FA, BS, nor XP patients. Rationale for chemoprevention trials is discussed. [Copyright &y& Elsevier]

Abstract: Objective: : To evaluate an association of Bloom syndrome (BS) phenotype with an in vivo prooxidant state. Methods: : The following endpoints were measured in 4 BS patients, their 6 parents, and 78 controls: a) leukocyte and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG); b) blood glutathione (GSSG and GSH), c) plasma levels of some plasma antioxidants (uric acid, UA, ascorbic acid, AA, α- and γ-tocopherol), and of glyoxal (Glx) and methylglyoxal (MGlx). Results: : Leukocyte 8-OHdG levels were significantly increased in the 4 BS patients vs. 40 controls (p =0.04), while the urinary 8-OHdG levels were non-significantly increased in BS patients. Glutathione disulfide levels and GSSG/GSH ratio were significantly decreased in BS patients vs. 44 controls (p =0.02). The plasma levels of UA in BS patients were significantly increased vs. 24 controls (p =0.005). No significant alterations were found in the in the plasma levels of Glx, MGlx, AA, and tocopherol. No changes in the tested parameters were found in the BS heterozygotes. Conclusion: : This report shows a significant increase in oxidative DNA damage in leukocytes and in plasma UA levels from 4 BS patients. Should these data be confirmed in more extensive BS patient groups, an involvement of oxidative stress in the clinical BS phenotype might be suggested. [Copyright &y& Elsevier]

Abstract: Objective: : To evaluate an in vivo pro-oxidant state in patients with ataxia telangiectasia (AT). Methods: : A set of oxidative stress endpoints were measured in 9 AT homozygotes, 16 AT heterozygotes (parents) and 83 controls (grouped in age ranges as for patients and parents, respectively). The following analytes were measured: (a) leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG); (b) blood glutathione (GSSG and GSH); and (c) plasma levels of glyoxal (Glx) and methylglyoxal (MGlx). Results: : AT patients displayed a significant decrease in blood GSSG (p =0.012) and in MGlx plasma concentrations (p =0.012). A non-significant decrease in the GSSG:GSH ratio (p =0.1) and a non-significant increase in 8-OHdG and Glx levels were observed in AT patients vs. young controls (age range 4–35 years). AT heterozygotes failed to display any significant changes vs. adult controls (age range 36–68 years). Conclusion: : No significant increase in oxidative stress biomarkers was detected in blood from AT patients. The decrease in GSSG and MGlx levels in AT patients may suggest an adaptive response to a pro-oxidant state in AT-related target organs. [Copyright &y& Elsevier]