Oxidative Stress and Antioxidant Status in High-Risk Prostate Cancer Subjects
Sanjeev Shukla, Janmejai Kumar Srivastava, Eswar Shankar, Rajnee Kanwal, Akbar Nawab, Haripaul Sharma, Natarajan Bhaskaran, Lee Ponsky, Pingfu Fu, Gregory T. MacLennan, Sanjay Gupta
Abstract
The oxidant/antioxidant balance has been implicated in the pathophysiology of prostate cancer. We investigated oxidative damage and antioxidant status in high-risk prostate cancer subjects. Reduced glutathione (GSH) levels were measured in erythrocytes, 8-hydroxydeoxyguanosine (8-OHdG) in leukocytes and plasma levels of catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R), glutathione S-transferase (GST), superoxide dismutase (SOD), and lipid peroxide products were measured in high-risk and age-matched healthy subjects. Serum PSA levels were significantly higher (p < 0.0001) in high-risk subjects, whereas GST (p < 0.0001) and GSH (p < 0.002) were higher in healthy controls. Levels of 8-OHdG, an oxidized nucleoside of DNA, were significantly increased (p < 0.0001) in high-risk subjects. No marked difference in the levels of CAT (p = 0.237), GSH-Px (p = 0.74), GSH-R (p = 0.344), SOD (p = 0.109), and lipid peroxide products (p = 0129) were observed between two groups. Pearson’s correlation between GST and PSA (r = −0.69 (p < 0.0001)), GST and 8-OHdG (r = −0.62 (p < 0.0004)), GSH and 8-OHdG (r= −0.39 (p = 0.038)), and CAT and GSH-Px (r= −0.33 (p = 0.04)) were found to be negatively correlated, whereas 8-OHdG and PSA were positively associated (r= 0.57 (p < 0.002). These results indicate a significant role of oxidative damage in prostate carcinogenesis, particularly during the early stages of development. In conclusion, our data support the importance of antioxidant defense as a valuable diagnostic and/or prognostic marker in prostate cancer.