title: In vivo prooxidant state in Werner syndrome (WS): results from three WS patients and two WS heterozygotes.
abstract: 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, alpha- and gamma-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 alpha- and gamma-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.
authors.affiliation: Italian National Cancer Institute, I-80131, Naples, Italy. gbpagano@tin.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pagano
authors.forename: Adriana
authors.initials: A
authors.lastname: Zatterale
authors.forename: Paolo
authors.initials: P
authors.lastname: Degan
authors.forename: Marco
authors.initials: M
authors.lastname: d'Ischia
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Kelly
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
authors.forename: Rita
authors.initials: R
authors.lastname: Calzone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
authors.forename: Christina
authors.initials: C
authors.lastname: Dunster
authors.forename: Aldo
authors.initials: A
authors.lastname: Giudice
authors.forename: Yurdanur
authors.initials: Y
authors.lastname: Kilinç
authors.forename: Ana
authors.initials: A
authors.lastname: Lloret
authors.forename: Paola
authors.initials: P
authors.lastname: Manini
authors.forename: Roberta
authors.initials: R
authors.lastname: Masella
authors.forename: Emilia
authors.initials: E
authors.lastname: Vuttariello
authors.forename: Michel
authors.initials: M
authors.lastname: Warnau
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000975:Antioxidants / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D006037:Glyoxal / Q000097:blood; D006579:Heterozygote; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011765:Pyruvaldehyde / Q000097:blood; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C075750:8-epi-prostaglandin F2alpha; D006037:Glyoxal; D011765:Pyruvaldehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine; D005978:Glutathione