Research Article: Changes of Oxidative Stress, Glutathione, and Its Dependent Antioxidant Enzyme Activities in Patients with Hepatocellular Carcinoma before and after Tumor Resection

Date Published: January 12, 2017

Publisher: Public Library of Science

Author(s): Shao-Bin Cheng, Hsiao-Tien Liu, Sin-Yuan Chen, Ping-Ting Lin, Chia-Yu Lai, Yi-Chia Huang, Sheng-Nan Lu.

http://doi.org/10.1371/journal.pone.0170016

Abstract

The changes in and relationship between oxidative stress and the glutathione (GSH) antioxidant system in the plasma and tissues of patients with hepatocellular carcinoma (HCC) before and after tumor resection have not been clearly determined. We investigated the changes in oxidative stress, GSH status and its dependent antioxidant enzyme activities in HCC patients before and after tumor resection, and to determine the association of oxidative stress with GSH and its dependent antioxidant enzyme activities in plasma and tissues. This study employed a cross-sectional design. Forty-four men and 16 women with HCC were recruited. Fasting blood was drawn on the day before the tumor resection and one month after the tumor resection. HCC tissue and adjacent normal liver tissue were obtained at the time of surgical resection. Patients had significantly increased plasma malondialdehyde (MDA) and oxidized-low density lipoprotein levels but decreased GSH and oxidized GSH levels before tumor resection compared with the corresponding post-resection values. GSH and trolox equivalent antioxidant capacity (TEAC) levels and activities of GSH peroxidase were significantly increased while MDA level was significantly lower in HCC tissue when compared with the adjacent normal tissue. The pre-resection plasma MDA level was significantly correlated with pre-resection plasma GSH concentration, and MDA level in HCC and adjacent normal tissues. Pre-resection plasma GSH concentration was significantly correlated with GSH and TEAC level in HCC tissue. HCC patients had increased oxidative stress, decreased GSH, and lower dependent antioxidant capacities before tumor resection. However, hepatocellular tumor had increased GSH and TEAC levels as well as GSH peroxidase activities which might protect itself against increased oxidative stress.

Partial Text

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the mortality rate has risen over the past decade. Among risk factors related to HCC, increased oxidative stress and decreased antioxidant capacities have been suggested to be contributors to HCC [1–5]. Although the human body has different antioxidant systems to defend against the generation of free radicals, oxidative stress is elevated when antioxidant capacities are low, which disrupts the balance between pro- and anti-oxidants and further causes the oncogenesis and tumor progression of HCC [6,7].

Table 1 shows the demographic and health characteristics of HCC patients. All patients’ ages ranged from 30 to 79 years with a mean age of 59.2 ± 11.1 y. The severity of liver disease in 58 patients was Child-Pugh class A, and in 2 patients was Child-Pugh class B. Of the 60 patients, 82% of patients had a first-time diagnosis of HCC [new case] and 18% of patients had recurrent HCC. Twenty-eight patients were in cancer stage I and 32 patients were in cancer stage II, and more than two-thirds of patients had poorly differentiated HCC. The post-resection levels of BMI, AST, and α-fetoprotein in HCC patients significantly decreased, whereas BUN and creatinine significantly increased when compared with the corresponding pre-resection values. However, serum albumin, creatinine, and BUN levels were within normal range at pre- and post-resection.

Carcinogenesis may progress or be enhanced if an imbalance between oxidative stress and antioxidant defense capacities occur. Our patients had increased oxidative stress (i.e., MDA and ox-LDL levels) and decreased GSH and GSSG levels before they underwent HCC resection; however, the expression of oxidative stress and GSH status was reversed after the HCC resection. This phenomenon supports the notion that increased oxidative stress is an important pathogenic mechanism of HCC [2,3,5], and suggests that GSH might be utilized and oxidized to GSSG in order to cope with increased oxidative stress during the development of HCC. A significant decrease in plasma GSH among HCC patients was also observed in a previous study [3]. In contrast to previous results indicating a decrease of GSH might be due to the increase in plasma GSSG level and GSH/GSSG ratio in HCC patients [3,17], the pre-resection plasma GSH/GSSG ratio in our HCC patients actually remained steady when compared to the post-resection level. Even though our HCC patients were under increased oxidative stress status and GSH-Rd activity was decreased before tumor resection, their GSH-Rd activities were not been fully exhausted so GSSG could still be reduced to GSH, thereby preventing the accumulation of GSSG. That is to say, the balance of GSH/GSSG redox could be maintained and was not completely shifted to the oxidized state in our HCC patients. In the antioxidant defense system, GSH-Px is considered to be the primary antioxidant enzyme, while GSH-ST serves as the secondary antioxidant enzyme. Our results revealed that the GSH-Px activity only slightly but not significantly decreased and GSH-ST activity was significantly increased before HCC resection, which implies that our patients tolerated the oxidative stress well. However, it is not known whether these properties of GSH, GSSG, and GSH-dependent antioxidant enzyme activities would persist if carcinogenesis progressed for a longer period.

The data herein indicate that although HCC patients had increased oxidative stress and decreased GSH-dependent antioxidant capacity in the circulation before tumor resection, hepatocellular tumor had increased GSH and TEAC levels as well as activities of GSH-Px which might protect itself against increased oxidative stress. It would be clinically valuable to know how hepatocellular tumors obtain more GSH from the circulation than adjacent normal tissue since there is currently no effective medical therapy for HCC.

 

Source:

http://doi.org/10.1371/journal.pone.0170016

 

0 0 vote
Article Rating
Subscribe
Notify of
guest
0 Comments
Inline Feedbacks
View all comments