ABSTRACT
Recent data from several studies suggest that oxidative stress is involved in the biochemical mechanisms that underlie neuropsychiatric disorders. The present study was designed to investigate oxidative stress status in depressive patients with gastric adenocarcinoma (GA) at TNM stage III. Oxidative stress, depression and expression of specific genes were monitored during a pretreatment period. Serum total antioxidant capacity, catalase, superoxide dismutase concentrations, and antisuperoxide anion capacity (A-ASC) were significantly decreased in depressive patients compared to control subjects, whereas serum malondialdehyde (MDA) levels were significantly increased. Importantly, the formation of 8-hydroxy-deoxyguanosine (8-OHdG) accumulated. Furthermore, SYBR Green real-time PCR revealed that the expression levels of human oxoguanine glycosylase 1 and APEX nuclease 1 (APEX1) were increased in depressive patients. Pearson correlation analysis revealed that depression was positively correlated with SAS, SCL-90, MDA, 8-OHdG and APEX1, but negatively correlated with A-ASC. Thus, this study confirms oxidative imbalance in depressive patients with GA, and oxidative stress may play a role in the onset and exacerbation of depression.
Subject(s)
Adenocarcinoma/complications , Depression/complications , Oxidative Stress/physiology , Stomach Neoplasms/complications , 8-Hydroxy-2'-Deoxyguanosine , Adult , Aged , Analysis of Variance , Antioxidants/metabolism , Catalase/blood , DNA Glycosylases/genetics , DNA Glycosylases/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Female , Gene Expression Regulation, Neoplastic/physiology , Humans , Male , Malondialdehyde/metabolism , Middle Aged , Superoxide Dismutase/bloodABSTRACT
OBJECTIVES: This study investigated the connection among the oxidative stress, depression and expression of specific genes involved in DNA-damage signaling pathways in patients with colorectal carcinoma (CRC). METHODS: A unique Dukes'C subset of patients with newly diagnosed colorectal adenocarcinoma were assessed using the Hamilton Depression Rating Scale (HAMD), Zung Self-rating Depression Scale (SDS), Zung Self-rating Anxiety Scale (SAS), Symptom Checklist 90 (SCL-90) and other multiple-item questionnaires. Oxidative-stress-related parameters in sera and the expression of genes were monitored during a pretreatment period. RESULTS: Eighty-two eligibility cases were divided into 2 groups based on an HAMD score cutoff of 20: the mean score was 28.29 in Group A (depression, n=52) and 16.50 in Group B (nondepression, n=30). The serum total antioxidant capacity, catalase, and superoxide dismutase concentrations were lower in Group A, whereas those of nitric oxide and malondialdehyde were higher in Group A. Importantly, the 8-hydroxy-deoxyguanosine level was higher in Group A than in Group B (P<.05). Microarray analysis revealed that the expressions of p34, PA26, and ABL were higher in Group A, whereas those of HRAD51, CR6, and XRCC3 were higher in Group B. CONCLUSION: Oxidative stress is capable of causing neuronal toxicity via lipid peroxidation, DNA damage, and abnormalities of gene expression, and therefore is a possible pathogenic mechanism underlying depression in patients with CRC.
