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During periods of psychological stress, excess amounts of free radicals are produced. Bilirubin oxidative metabolites (biopyrrins; BOM) are generated from bilirubin as a result of its scavenging action against free radicals. We investigated whether the urinary excretion of biopyrrins is altered by anxiolytics. In the present study, mice were immobilized for a period of 6 hr. Alprazolam (0.1-1 mg/kg of body-weight) was administered 30 min. before subjecting the animals to acute stress. The BOM concentrations in urine and the corticosterone levels in serum were measured by ELISA with an anti-bilirubin antibody and EIA, respectively. We observed an increase in urinary biopyrrins in stressed mice in comparison with non-stressed mice and a decrease after the treatment of stressed animals with alprazolam. A correlation between urinary BOM and serum corticosterone levels was found. Urinary levels of biopyrrins might be used to assess the response to anxiolytics prescribed during acute stress periods., (© 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.)

Emotional stress can be viewed as a cause of adverse circumstances that induces a wide range of biochemical and behavioural changes. Oxidative stress is a critical route of damage in various psychological stress-induced disorders such as depression. Antidepressants are widely prescribed to treat these conditions; however, no animal study has investigated the effect of selective serotonin reuptake inhibitors (SSRIs) on the levels of intracellular reactive oxygen species in peripheral blood leucocytes of stressed mice. In this study, mice were immobilized for a period of 6 hr. Fluoxetine (5 mg/kg of body-weight) was administered 30 min. before subjecting the animals to acute stress. The level of intracellular reactive oxygen species in leucocytes of the peripheral blood of stressed mice was investigated using a 2',7'-dichlorofluorescein diacetate probe, and the antioxidant response of fluoxetine was evaluated by superoxide dismutase, diaphorase, catalase and reduced glutathione. Our results show that restraint stress significantly increases the generation of reactive oxygen species in the peripheral defence cells. Treatment with fluoxetine partially reverses the adverse effects of stress. The improvement in cellular oxidative status may be an important mechanism underlying the protective pharmacological effects of fluoxetine, which are clinically observed in the treatment of depressive disorders., (© 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.)