Abstract
The aim of the present study was to assess the effects of l-buthionine-(S,R)-sulfoximine (BSO), a glutathione (GSH) synthesis inhibitor, and GBR 12909, a dopamine reuptake inhibitor, administered alone or in combination to Sprague-Dawley rats during early postnatal development (p5–p16), on the levels of reactive oxygen species (ROS), lipid peroxidation (LP) and the activities of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR) in peripheral tissues (liver, kidney) and selected brain structures (prefrontal cortex, PFC; hippocampus, HIP; and striatum, STR) of 16-day-old rats. The studied parameters were analyzed with reference to the content of GSH and sulfur amino acids, methionine (Met) and cysteine (Cys) described in our previous study. This analysis showed that treatment with a BSO + GBR 12909 combination caused significant decreases in the lipid peroxidation levels in the PFC and HIP, in spite of there being no changes in ROS. The reduction of lipid peroxidation indicates a weakening of the oxidative power of the cells, and a shift in balance in favor of reducing processes. Such changes in cellular redox signaling in the PFC and HIP during early postnatal development may result in functional changes in adulthood.
Highlights
There is a growing body of evidence implicating oxidative stress mechanisms in the pathophysiology of schizophrenia [1,2,3,4,5]
superoxide dismutase (SOD) activity is expressed in U/mg of protein, the activity of CAT is expressed in μmol/mg of protein/min
glutathione peroxidase (GPx) and glutathione disulfide reductase (GR) activities are expressed in nmol/mg of protein/min (the amount of enzyme that causes the oxidation of 1 nmol of nicotinamide adenine dinucleotide phosphate (NADPH) to NADP+ during 1 min per mg of protein)
Summary
There is a growing body of evidence implicating oxidative stress mechanisms in the pathophysiology of schizophrenia [1,2,3,4,5]. Antioxidants 2020, 9, 538 hydrogen peroxide (H2 O2 ), peroxynitrite (ONOO− ), aldehydes, quinones and disulfides [7]. All these oxidants significantly affect the regulation of the cellular redox state by modulating sulfhydryl (–SH). Residues of Cys and thioeter groups of methionine (Met) located in the active sites of many proteins [7]. These redox molecules are usually susceptible to two-electron oxidants. The adequate levels of thiol antioxidants, like GSH, Cys and Trxred , which control the functions of the thiol-containing proteins, are essential for maintaining the physiological redox status of cells
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