title: Disturbances in the glutathione/ophthalmate redox buffer system in the woodchuck model of hepatitis virus-induced hepatocellular carcinoma.
abstract: Purpose. The incidence of liver tumors is rising in USA. The purpose of this study was to evaluate liver oxido-reductive status in the presence of chronic liver disease and hepatocellular carcinoma (HCC). Methods. Glutathione species and ophthalmate (OA) concentrations were measured by LC-MS in processed plasma and red blood cells (RBC) from infected Woodchuck with hepatitis virus (WHV). Blood samples were obtained from: (i) infected animals with tumors (WHV+/HCC+), (ii) infected animals without tumors (WHV+/HCC-) and (iii) healthy animals (WHC-/HCC-). Results. The concentration of reduced glutathione (GSH) and the ratio GSH/GSG were lower in plasma from WHV+/HCC+ animals when compared to WHV+/HCC- and WHV-/HCC- (P < 0.01). In contrast, the concentration of oxidized glutathione (GSSG) was found to be higher in plasma from WHV+/HCC+ animals when compared to WHV+/HCC- and WHV-/HCC- (P < 0.01). The Glutathione species and its ratio from the RBC compartment were similar among all groups. OA concentration in both plasma and RBC was significantly higher from WHV+/HCC+ when compared to WHV+/HCC- and WHV-/HCC- (P < 0.01). Conclusions. Disturbances of the glutathione redox buffer system and higher concentrations of OA were found in the WCV+/HCC+ animal model. The role of these compounds as biomarkers of early tumor development in patients with end stage liver disease remains to be determined.
authors.affiliation: Department of Surgery, Case Western Reserve University School of Medicine and University Hospitals, Case Medical Center, Cleveland, OH 44106-7029, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Andres Ibarra
authors.forename: R
authors.initials: R
authors.lastname: Abbas
authors.forename: R S
authors.initials: RS
authors.lastname: Kombu
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Jacobs
authors.forename: Z
authors.initials: Z
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Brunengraber
authors.forename: J R
authors.initials: JR
authors.lastname: Sanabria