High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Abstract

Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through ROS and ROS-driven oxidative stress, the role of anti-oxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the anti-oxidant response of the lung correlated well with that of RBC. We then proceeded to test whether differences of RBC anti-oxidant response would predict the pneumonitis development in patients. SOD, GPX, CAT activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in fifteen eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the anti-oxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs. 6.8 unit/mg for median SOD, 16.5 vs. 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pre-treatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

Nitric oxide, afferent sensory nerves, and antioxidative enzymes in the mechanism of protection mediated by tricarbonyldichlororuthenium(II) dimer and sodium hydrosulfide against aspirin-induced gastric damage

“…Together these observations suggest that mainly H 2 S but to lesser degree of CO can promote an antioxidative response in gastric mucosa at the mRNA level for both enzymes. It has previously been reported that differences in GPx-1 and SOD activities could serve as a marker of the pathological condition [41]. Our present observations support recent findings that H 2 S-releasing Lawesson's reagent or another CO donor, dimanganese decacarbonyl, protected gastric mucosa against alendronate-induced gastric damage via regulation of oxidative stress as manifested by an increase in reduced glutathione content and a decrease in MDA content in rat gastric mucosa injured by alendronate [42,43].…”

Basal levels of glutathione peroxidase correlate with onset of radiation induced lung disease in inbred mouse strains

“…Second, because baseline GPx activity in the serum was correlated with tissue fibrosis in these mice, serum levels of this enzyme may be a useful biomarker, although they were not predictive of the pulmonary activity of the same enzyme. These findings are supported by one clinical report wherein the lower levels of RBC GPx activity, both pretreatment and after radiotherapy, were observed in lung cancer patients developing pneumonitis compared with those in patients who did not develop pneumonitis following radiotherapy (21).…”

“…GSH not only directly scavenges ROS but is also required for the catalytic activity of GPx. These cellular antioxidants, however, may not be enough to overcome the primary oxidative damage caused by radiation exposure because of the excessive generation of ROS, a condition termed as oxidative stress (3,18,21). It is therefore possible that an individual's susceptibility toward radiation-induced lung diseases could depend on how efficiently the lung cells are able to manage this primary injury (21).…”

Antioxidant Enzymes in Gestational Diabetes: A Study on a Kuwaiti Population

“…Further investigations may suggest modified treatment program for GDM patients at early pregnancy. Park and Associates [39] found striking differences in the anti-oxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs. 6.8 unit/mg for median SOD, 16.5 vs. 10.7 nmol/min/mg for median GPX).…”