The impact of chronic stress on intracellular redox balance: A systems level analysis

Chronic psychosocial stress is implicated in the onset and progression of noncommunicable diseases, and mechanisms underlying this relationship include alterations to the intracellular redox state. However, such changes are often investigated in isolation, with few studies adopting a system level approach. Here, male Wistar rats were exposed to 9.5 weeks of chronic unpredictable mild stress and redox status assays were subsequently performed on cardiac, hepatic, and brain tissues versus matched controls. The stressed rats displayed an anxious phenotype, with lowered plasma corticosterone levels (p = 0.04 vs. Controls) and higher plasma epinephrine concentrations (p = 0.03 vs. Controls). Our findings showed organ-specific redox profiles, with stressed rats displaying increased myocardial lipid peroxidation (p = 0.04 vs. Controls) in the presence of elevated nonenzymatic antioxidant capacity (p = 0.04 vs. Controls). Conversely, hepatic tissues of stressed rats exhibited lowered nonenzymatic antioxidant capacity (p < 0.001 vs. Controls) together with increased superoxide dismutase (SOD) activity (p = 0.05 vs. Controls). The brain displayed region-specific antioxidant perturbations, with increased SOD activity (p = 0.01 vs. Controls) in the prefrontal cortex of the stressed rats. These findings reveal distinct stress-related organ-specific vulnerability to redox perturbations and may provide novel insights into putative therapeutic targets.

Automated summary

Chronic psychosocial stress is associated with noncommunicable diseases and affects the intracellular redox state. In this study, male Wistar rats were exposed to chronic unpredictable mild stress and redox status assays were performed on cardiac, hepatic, and brain tissues. The stressed rats showed increased anxiety, decreased corticosterone levels, and elevated epinephrine concentrations. Organ-specific redox profiles were observed, with the stressed rats showing increased myocardial lipid peroxidation and nonenzymatic antioxidant capacity in the heart, decreased nonenzymatic antioxidant capacity and increased superoxide dismutase activity in the liver, and increased superoxide dismutase activity in the prefrontal cortex of the brain. These findings highlight the organ-specific vulnerability to redox perturbations caused by chronic stress and provide potential therapeutic targets.