Chronic environmental stress is associated with reactive oxygen species (ROS) overproduction and the pathogenesis of depression. The purpose of this study was to evaluate biochemical and molecular changes associated with ROS generation in the brains of rats submitted to chronic variable stress. Male Wistar rats (50–55 days old, weighing 200–250 g) were divided in two groups (n = 10): control and stressed. Rats in the stressed group were exposed to stress conditions for 40 days. The animals were decapitated and the brain samples were collected. In prefrontal cortex, we measured the following biochemical parameters: lipid peroxidation and concentration of glutathione—GSH, GSSG, GSH/GSSG ratio, glutathione peroxidase, and glutathione reductase activities. In the hippocampus marker of DNA, oxidative damage and expression of DNA-repairing genes (Ogg1, MsrA) and gene-encoding antioxidative transcriptional factor (Nrf2) were determined. The results demonstrate indirect evidence of ROS overproduction and presence of oxidative stress. They also reveal disruption of oxidative defense systems (decreased GR activity, diminished GSH/GSSG ratio, and decreased Nrf2 expression) and activation of the oxidative DNA repair system (increased Ogg1 and MsrA expression). Together, the presented data suggest that independent activation of oxidative stress response genes occurs in chronic variable stress conditions.

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Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases, especially in developed countries. One group of substances with a potential use in the treatment of NAFLD are plant polyphenols, represented by resveratrol. The aim of this study was to evaluate the effect of resveratrol on steatosis and oxidative stress in HepG2 cells. The steatosis of cells was carried out using free fatty acids: oleic or palmitic acid and their mixtures. Steatosis was visualized using the intracellular lipid staining by Nile Red dye with a fluorescence microscope. This study also determined the viability of cells and mitochondrial membrane potential. The current study showed that fatty acids and their mixtures induced fat overloading in HepG2 cells. In the group of cells incubated with oleic acid (OA), observed changes were moderate with prevailing micro-vesicular steatosis. In case of cells incubated with palmitic acid (PA) and the mixtures of fatty acids, micro- and macro-vacuolar steatosis occurred in most of the cells. Resveratrol decreased steatosis in HepG2 cells induced by OA, PA, as well as their mixtures, and in most of experimental groups did not reduce cells viability. Resveratrol reduced the oxidative stress in HepG2 cells treated with fatty acids mixtures.

The observed changes may indicate an increased activity of the enzyme system preventing oxidation, which appears to be the effect of the reaction on the severity of oxidative stress during the combined treatment with rosuvastatin and antidepressants.