Evidence of oxidative stress in the circulation of ovarian cancer patients

https://doi.org/10.1016/j.cccn.2003.08.017Get rights and content

Abstract

Background: Ovarian cancer is the leading cause of death due to gynecological malignancies among women. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant mechanisms. The present study was conducted to investigate the extent of oxidative stress and the levels of antioxidants in the circulation of ovarian cancer patients. Methods: Plasma thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) and the levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), vitamin C and vitamin E were estimated in the circulation of 30 ovarian cancer patients and an equal number of age-matched normal subjects as control. Results: Significantly increased concentrations of plasma TBARS and CD and significantly lowered levels of SOD, CAT, vitamin C and vitamin E were observed in ovarian cancer patients as compared with normal subjects. Conclusion: The low levels of SOD, CAT, vitamin C and vitamin E in the plasma of ovarian cancer patients may be due to their increased utilization to scavenge lipid peroxides as well as their sequestration by tumor cells. Increased levels of lipid peroxidation may be due to excessive oxidative stress caused by incessant ovulation or epithelial inflammation.

Introduction

Ovarian cancer is the leading cause of death due to gynecological malignancies and is the fifth most common cause of mortality from cancers among women [1]. In India, 15% of all gynecological cancers is ovarian malignancy [2] and it represents the greatest clinical challenge. Risk factors for ovarian carcinoma include inflammation, excessive number of life time ovulations, increases in steroid hormone levels, heredity, infertility, oral contraceptive pills, age, asbestos, talc and reproductive factors such as nulliparity [3], [4]. Ovarian cancer at an early stage is asymptomatic, but later the main symptoms include abdominal swelling, bloating, pain and pressure [5]. Recent molecular studies have shown that ovarian cancer has acquired genetic alterations of oncogenes and tumor suppressor genes such as BRCA1, p53, nm23 and K-ras, which may be due to inflammation and oxidative stress [6].

Oxidative stress is potentially harmful to cells and reactive oxygen species (ROS) are known to be induced in the initiation and progression of cancer [7]. ROS can damage cellular components such as lipids, proteins and DNA, affecting enzyme activity and membrane function [8]. Humans are well endowed with enzymic and non-enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione, ascorbic acid (vitamin C) and alpha-tocopheral (vitamin E) [9]. Under conditions of excessive oxidative stress, however, cellular antioxidants are depleted [10].

In recent years, there has been a growing interest in studying the role played by lipid peroxidation and antioxidants in ovarian cancer patients [11], [12]. Therefore, the aim of our study was to assess the lipid peroxidation as indicated by TBARS and conjugated dienes and antioxidants such as SOD, CAT, vitamin C and vitamin E in circulation of women with ovarian cancer and to compare our findings with age-matched controls.

Section snippets

Subjects

Thirty newly diagnosed ovarian cancer patients who obtained a transvaginal ultrasonography (USG) at Rajah Muthiah Medical College and Hospital, Annamalai University, Annamalainagar, Tamil Nadu, India, and who had not undergone any previous treatment for their tumors were selected for the study. The mean age of the patients were 58.6±7.3 years with a range of 50–70 years. Thirty healthy volunteers (all women 58.2±7.6 years; 50–70 years) served as control subjects. Oral consent was obtained from

Results

Table 1 shows the level of lipid peroxidation in plasma of normal and ovarian cancer patients. Lipid peroxidation as assessed by TBARS level was significantly higher in ovarian cancer patients as compared with normal subjects. Plasma conjugated dienes were also significantly increased in ovarian cancer patients as compared with normal subjects.

Table 2 shows the level of antioxidants in the circulation of normal and ovarian cancer patients. The enzymatic antioxidants such as SOD and CAT in the

Discussion

Oxidative stress is due to a disturbance in the balance between the production of ROS and the efficiency of the antioxidant defense. In other words, oxidative stress results if excessive production of ROS overwhelms the antioxidant defense system or when there is a significant decrease or lack of antioxidant defense [20]. Potential biological targets for free radical attack include lipids, proteins and nucleic acids [21]. The epoxides generated due to increased oxidative stress may

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