Total Antioxidant Status (TAS), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) in Oropharyngeal Cancer Associated with EBV Infection

Abstract

A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.

Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in patients with diabetes mellitus type 2 infected with Epstein-Barr virus

“…There are reports about malignancies developing more frequently in diabetic patients, especially in individuals with DM2 [37]. Our previous study revealed that in cancer patients with EBV infection there was decrease in the value of antioxidant enzymes [38]. The present research showed that in diabetic patients infected with EBV the activity of SOD and GPx was PLOS ONE also lowered.…”

Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD) in Oropharyngeal Cancer Associated with EBV and HPV Coinfection

“…In the next study, decreased activity of antioxidant enzymes (GPx and SOD) in oropharyngeal cancer tissue, particularly in EBV-positive patients was stated. Significantly lower GPx and SOD values were found in patients with reactivation of EBV infection [30].…”

The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants

“…Increased GPx levels were observed in many tumor cells, such as the oral squamous cell carcinoma (OSCC) [ 185 ], lung [ 186 ], colorectal [ 187 ], breast [ 188 ], and brain tumor [ 189 ] patients, compared with healthy controls. This can be explained by the fact that the tumor has high levels of oxidative stress; the body increases then the antioxidant system levels to compensate the increased levels of ROS as a natural defense against cancer [ 190 ]. Adenovirus-mediated human glutathione peroxidase gene (AdGPx) overexpression reduced the growth of pancreatic cancer cells in vitro and in vivo models.…”