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.
Highlights
Hepatocellular carcinoma (HCC) is the fourth most common cancer in the world, with a high lethality index [1]. It develops and flourishes mostly in patients with liver disease, and its incidence is on the rise in United States due to an increase in hepatitis C virus (HCV) infection and nonalcoholic steatohepatitis (NASH) [1]. 80% of these tumors are surgically untreated at the time of diagnosis because of an advanced stage or due to a medical condition that prohibits resection or transplantation, the only curative treatments [2]
We have shown that disturbances of the glutathione redox buffer system and OA were present in the VX2 rabbit model of secondary liver tumors as early as 14 days after tumor implantation and these changes were caused by an oxidative stress reaction within the tumor surroundings in response to the neoplastic growth [11]
We hypothesized that these changes can be detected in animals with chronic viral hepatitisinduced HCC and that complete ablation of the tumors will not altered the disturbances of the glutathione/OA buffer system observed in early tumor development, since these are produced in the surrounding healthy liver tissues in reaction to a growing mass in need for energy substrates
Summary
Hepatocellular carcinoma (HCC) is the fourth most common cancer in the world, with a high lethality index [1]. We hypothesized that these changes can be detected in animals with chronic viral hepatitisinduced HCC and that complete ablation of the tumors will not altered the disturbances of the glutathione/OA buffer system observed in early tumor development, since these are produced in the surrounding healthy liver tissues in reaction to a growing mass in need for energy substrates. To answer this question we made use of the well-established woodchuck hepatitis virus- (WHV-) induced HCC model [12, 13]. We found a significant decrease in the GSH/GSSG ratio and an increase in the concentrations of OA in plasma from infected animals with tumors when compared to both infected animals without tumors and healthy controls (noninfected animals without tumors)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
