Immobilization stress causes extra-cellular oxidant–antioxidant imbalance in rats: Restoration by L-NAME and vitamin E

Stress has been shown to be associated with altered homeostasis that may lead to oxidant–antioxidant imbalance. Non-enzymatic antioxidants are important regulators of reactive oxygen species produced in extra-cellular milieu and represent the first line of defense against them. Extra-cellular non-enzymatic antioxidants may be disturbed by the production of superoxide and nitric oxide and this has not been studied in stressful situation previously. In the present study, effects of immobilization stress (IS), both acute (IS × 1) and repeated (IS × 7) were assessed on extra-cellular total antioxidant capacity measured as plasma ferric reducing antioxidant power (FRAP) and protein sulfhydryls, and oxidative stress measured as leukocyte superoxide generation, plasma nitric oxide production (total nitrates and nitrites, NOx) and lipid peroxides in rats. Effects of pretreatment with nitric oxide synthase (NOS) inhibitors and vitamin E were also studied on these biochemical parameters. The results showed that both IS × 1 and IS × 7 resulted in extra-cellular oxidant–antioxidant imbalance as oxidant generation was increased and non-enzymatic antioxidants were depleted. Pretreatment either with NOS inhibitors or vitamin E restored stress-induced extracellular oxidant–antioxidant imbalance implying their potential role as antioxidants. Our data suggest that there is extra-cellular oxidant–antioxidant imbalance in the stressed rats, with greater magnitude of severity in repeated stress paradigm. Augmentation of antioxidant defenses might be beneficial in long-term stress.