Hindawi Publishing Corporation
HPB Surgery
Volume 2011, Article ID 709052, 8 pages
doi:10.1155/2011/709052
Research Article
The Dynamics of Glutathione Species and Ophthalmate
Concentrations in Plasma from the VX2 Rabbit Model of
Secondary Liver Tumors
R. Abbas,
1
R. S. Kombu,
2
R. A. Ibarra,
1, 2
K. K. Goyal,
1
H. Brunengraber,
1, 2
and J. R. Sanabria
1, 2
1
Division of Transplant and Hepatobiliary Surgery, Department of Surgery, Case Western Reserve University School of Medicine and
University Hospitals, Case Medical Center, 11100 Euclid Avenue, Lakeside 7510, PS 5047, Cleveland, OH 44106, USA
2
Department of Nutrition, Case Western Reserve University School of Medicine and University Hospitals, Case Medical Center,
11100 Euclid Avenue, Lakeside 7510, PS 5047, Cleveland, OH 44106, USA
Correspondence should be addressed to J. R. Sanabria, juan.sanabria@uhhospitals.org
Received 26 June 2010; Accepted 11 January 2011
Academic Editor: Christos G. Dervenis
Copyright © 2011 R. Abbas et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose. Available tumor markers have low sensitivity/specificity for the diagnosis of liver tumors. The present study was designed
to evaluate the oxidoreductive status of the liver as surrogates of tumor subsistence and growth. Methods. Glutathione species
(GSH:GSSG), ophthalmate (OA) concentrations, and their turnover were measured in plasma of rabbits (n = 6) in their healthy
state and in the state of tumor growth after implantation of the VX2 carcinoma in their liver. Tumors were allowed to grow for a
period of 14 days when rabbits were sacrificed. Livers were removed and cysteine concentration was measured in liver tissue. Results.
Tumor growth was found in 100% of the rabbits. Concentration and labeling of GSH/GSSG were similar in experimental animals
before and after tumor implantation and to sham animals. In contrast, OA concentration increased significantly in experimental
animals after tumor implantation when compared to same animals prior to tumor implantation and to sham animals (P<.05).
The concentration of cysteine, a precursor of GSH, was found to be significantly lower in the liver tissue adjacent to the tumor
(P<.05). Conclusion. Disturbances in the oxidoreductive state of livers appear to be a surrogate of early tumor growth.
1. Introduction
Liver tumors are the third most common malignancies of the
gastrointestinal tract worldwide [1]. In the Western World,
secondary liver tumors are more frequent than primary
ones, even though the incidence of hepatocellular carcinoma
(HCC) has been increasing over the last 20 years, especially
in males [2]. Nearly 80% of liver tumors are diagnosed
in advanced stages precluding curative therapies [3], and
tumor markers for the early detection of liver growth
lack high levels of sensitivity and specificity. Currently, α-
fetoprotein (AFP) and carbohydrate antigen 19.9 (CA19.9)
are the most frequently used serum markers to detect hep-
atocellular carcinoma and cholangiocarcinoma, respectively
[4–9]. Carcinoembryonic antigen (CEA) is frequently used
for detection and followup of colorectal liver metastases
[10]; however it may be increased in many other medical
conditions. The ideal biomarker for early detection of liver
cancer would be specific for the malignant condition and
sensitive enough to detect the neoplasm at an early stage,
when treatment is still possible [11]. Serum metabolites
related to oxidative stress are thought to be a potential
biomarker for the early detection of cancer [12, 13].
Patients with advanced malignancy are typically in a
catabolic state. Tumor necrosis factor-α(TNF-α) and other
cytokines have been implicated in promoting a low-energy
intake with increased energy expenditure and negative
energy balance, likely due to tumor growth [12]. Mantovani
et al. found a significant elevation in TNF and IL-6 along
with a reduced activity of the enzyme glutathione peroxidase
in patients with advanced stages of various cancers (stage III
or IV) [13]. Glutathione peroxidase is considered a surrogate