TY - JOUR
T1 - In vivo prooxidant state in Werner syndrome (WS)
T2 - Results from three WS patients and two WS heterozygotes
AU - Pagano, Giovanni
AU - Zatterale, Adriana
AU - Degan, Paolo
AU - D'Ischia, Marco
AU - Kelly, Frank J.
AU - Pallardó, Federico V.
AU - Calzone, Rita
AU - Castello, Giuseppe
AU - Dunster, Christina
AU - Giudice, Aldo
AU - Kilinç, Yurdanur
AU - Lloret, Ana
AU - Manini, Paola
AU - Masella, Roberta
AU - Vuttariello, Emilia
AU - Warnau, Michel
PY - 2005/5
Y1 - 2005/5
N2 - The hypothesis was tested that Werner syndrome (WS) phenotype might be associated with an in vivo prooxidant state. A set of redox-related endpoints were measured in three WS patients, two of their parents, and 99 controls within a study of some cancer-prone and/or ageing-related genetic disorders. The following analytes were measured: (a) leukocyte 8-hydroxy-2′-deoxyguanosine; (b) glutathione from whole blood, and (c) plasma levels of glyoxal, methylglyoxal, 8-isoprostane, and some plasma antioxidants (uric acid, ascorbic acid, α- and γ-tocopherol). Leukocyte 8-hydroxy-2′-deoxyguanosine levels showed a significant increase in the 3 WS patients vs. 85 controls (p <10-7). The disulfide glutathione:glutahione ratio was significantly altered in WS patients (p = 0.005). Glyoxal and methylglyoxal levels were significantly increased (p = 0.018 and p = 0.007, respectively). The plasma levels of uric acid (p = 0.002) and ascorbic acid (p = 0.003) were also increased significantly in WS patients and in their parents. No significant alterations were found in the plasma levels of α- and γ-tocopherol, nor of 8-isoprostane. This is the first report of in vivo alterations of oxidative stress parameters in WS patients. Further investigations on more extensive study populations are warranted to verify the relevance of an in vivo prooxidant state in WS patients.
AB - The hypothesis was tested that Werner syndrome (WS) phenotype might be associated with an in vivo prooxidant state. A set of redox-related endpoints were measured in three WS patients, two of their parents, and 99 controls within a study of some cancer-prone and/or ageing-related genetic disorders. The following analytes were measured: (a) leukocyte 8-hydroxy-2′-deoxyguanosine; (b) glutathione from whole blood, and (c) plasma levels of glyoxal, methylglyoxal, 8-isoprostane, and some plasma antioxidants (uric acid, ascorbic acid, α- and γ-tocopherol). Leukocyte 8-hydroxy-2′-deoxyguanosine levels showed a significant increase in the 3 WS patients vs. 85 controls (p <10-7). The disulfide glutathione:glutahione ratio was significantly altered in WS patients (p = 0.005). Glyoxal and methylglyoxal levels were significantly increased (p = 0.018 and p = 0.007, respectively). The plasma levels of uric acid (p = 0.002) and ascorbic acid (p = 0.003) were also increased significantly in WS patients and in their parents. No significant alterations were found in the plasma levels of α- and γ-tocopherol, nor of 8-isoprostane. This is the first report of in vivo alterations of oxidative stress parameters in WS patients. Further investigations on more extensive study populations are warranted to verify the relevance of an in vivo prooxidant state in WS patients.
KW - Glutathione
KW - Glyoxal
KW - Methylglyoxal
KW - Oxidative DNA damage
KW - Prooxidant state
KW - Werner syndrome
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U2 - 10.1080/10715760500092683
DO - 10.1080/10715760500092683
M3 - Article
C2 - 16036329
AN - SCOPUS:21044447217
VL - 39
SP - 529
EP - 533
JO - Free Radical Research
JF - Free Radical Research
SN - 1071-5762
IS - 5
ER -