title: Interplay between the pro-oxidant and antioxidant systems and proinflammatory cytokine levels, in relation to iron metabolism and the erythron in depression.
abstract: As there is strong evidence for inflammation and oxidative stress in depression, the aim of this study was to elucidate the relationship between oxidative imbalance and cellular immune response and to ask whether these processes are linked with iron metabolism in depressed patients. Blood was collected from patients diagnosed with recurrent depressive disorder (n=15) and from healthy controls (n=19). Whole-blood reduced glutathione (GSH), erythrocyte superoxide dismutase (SOD-1), glutathione peroxidase (GPx-1), glutathione reductase, malondialdehyde (MDA), and methemoglobin (MetHb) and plasma H₂O₂ were assayed spectrophotometrically. The serum heme oxygenase 1 (HO-1), cytokine, neopterin, and iron statuses were measured by ELISA. DNA damage was analyzed by comet assay. Serum concentrations of ferritin and soluble transferrin receptor were assayed by ELISA. MetHb saturation was analyzed spectrophotometrically in red blood cell hemolysate. The erythron variables were measured using a hematological analyzer. We observed a significant decrease in GPx-1 and SOD-1 activities and decreased levels of HO-1 and GSH in depressed patients compared to controls. Conversely, compared with controls, we found increased concentrations of MDA and H₂O₂ and more DNA damage in depressed patients. Furthermore, the levels of the proinflammatory cytokine interleukin-6 and of neopterin were increased in depressed patients along with decreased hemoglobin and hematocrit. A strong association between antioxidant defense, cytokine levels, and iron homeostasis was also revealed. These findings show that depression is associated with increased oxidative stress, inflammation, and restrictions on the available iron supply for red blood cell production. Furthermore, decreased antioxidant defense correlates with an increased cellular inflammatory response, whereas both concur with erythron and iron status, the latter explained by significant canonical correlations with the set of free radical scavenging enzymes and proinflammatory enzymes. The strong links between immune function, oxidative stress, and iron homeostasis suggest the presence of a self-sustaining multipathway mechanism that may progressively worsen, i.e., throughout accumulation of oxidative damage, producing the functional and structural consequences associated with depression. Hence, identifying viable therapeutic strategies to tackle oxidative stress and accompanying physiological disturbances, including inflammation and anemia, of chronic disease provides more opportunities for the treatment and, ultimately, prevention of depression.
authors.affiliation: Department of Biochemistry, Collegium Medicum UMK, 85-092 Bydgoszcz, Poland. joanna.rybka@scienceventure.eu
authors.forename: Joanna
authors.initials: J
authors.lastname: Rybka
authors.forename: Kornelia
authors.initials: K
authors.lastname: Kędziora-Kornatowska
authors.forename: Patrycja
authors.initials: P
authors.lastname: Banaś-Leżańska
authors.forename: Ireneusz
authors.initials: I
authors.lastname: Majsterek
authors.forename: Livia A
authors.initials: LA
authors.lastname: Carvalho
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cattaneo
authors.forename: Christoph
authors.initials: C
authors.lastname: Anacker
authors.forename: Józef
authors.initials: J
authors.lastname: Kędziora
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D003866:Depressive Disorder / Q000097:blood* / Q000473:pathology; D005260:Female; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D005980:Glutathione Reductase / Q000097:blood; D051547:Heme Oxygenase-1 / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D007111:Immunity, Cellular; D007249:Inflammation / Q000097:blood / Q000378:metabolism / Q000473:pathology; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000097:blood; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D016207:Cytokines; C000606290:SOD1 protein, human; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007501:Iron; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005980:Glutathione Reductase; D005978:Glutathione; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
keywords: Depression; Free radicals; GPx-1; Inflammation; Iron; MDA; Macrophage function; Oxidative stress