Evaluation of trace elements associated with antioxidant enzymes in blood of primary epithelial ovarian cancer patients.

Epithelial ovarian cancer (EOC) has been associated with oxidative stress (OS) due to epithelial inflammation which makes ovaries more vulnerable to the deleterious effects of reactive oxygen species (ROS). However, antioxidant enzymes (AOEs) such as manganese-superoxide dismutase (Mn-SOD), copper,zinc-superoxide dismutase (Cu,Zn-SOD) and glutathione peroxidase (GPx1) protect cells against the biological damage of ROS-induced OS and support cancer prevention by maintaining normal cell cycle progression, inhibiting proliferation, tumor invasion, angiogenesis, inflammation or inducing apoptosis. In the present study, we aimed to measure the levels of trace elements [manganese (Mn), copper (Cu), zinc (Zn) and selenium (Se)] which are structurally and/or functionally associated with the AOEs by inductively coupled plasma/mass-spectrometry (ICP/MS) in blood samples of patients with EOC (M, n = 26) and compare the data with healthy subjects (C, n = 46). Serous EOC (M1, n = 18) data were also evaluated according to the tumor grading [well or moderately well differentiated (G 1-2) vs. poorly differentiated or undifferentiated (G3)] and staging of disease [stage I-II (SI-II) vs. stage III (SIII)]. We obtained; i) The Mn and Se levels of M were significantly lower than C, ii) only Mn levels were changed [(G3(Mn) < G 1-2 (Mn)] in M1, iii) significant correlations were observed between [Cu and Zn levels (r = 0.701, p = 0.036) in G 1-2 and (r = 0.686, p = 0.041) in G3; Cu and Se levels (r = 0.960, p = 0.000) in G3; Mn levels and Mn-SOD expression (r = 0.551, p = 0.006) in M, (r = 0.857, p = 0.007) in G 1-2 and (r = 0.690, p = 0.056) in G3; Se levels and erythrocyte GPx1 activity (r = 0.660, p = 0.053) in G 1-2 ; Se levels and erythrocyte Cu,Zn-SOD activity (r = 0.693, p = 0.038) in G3]. The study revealed that trace elements, particularly low Mn and Se levels along with high Cu/Se ratios might be of value in all histologic subtypes of EOC. Although Mn level was important in terms of discriminating tumor grades, positive correlation between Cu-Se levels was also remarkable in patients with G 1-2 tumors of M1. Moreover, high erythrocyte Cu/Se ratios might be a favourable marker for EOC.

Assessment of oxidant-antioxidant status alterations with tumor biomarkers and reproductive system hormones in uterine MYOMAS.

OBJECTIVES: Uterine myomas (UM) are responsible for significant morbidity and have adverse effects on quality of life in women. Reactive oxygen species (ROS) and antioxidant enzymes (AOE), as well as sex steroids play important roles in the reproductive physiology processes. Thus, we aimed to investigate the role of oxidant-antioxidant status in UM by measuring the AOE activities and lipid peroxidation (LPO) levels. This is the first study assessing these parameters together in UM based on also menopausal status and evaluating possible correlations between AOE activities, LPO markers, tumor biomarkers, female reproductive system hormone levels, comprehensively. STUDY DESIGN: The study group consisted of patients who have undergone surgical resection with confirmed pathology of uterine myoma (UM, n = 25) and divided into subgroups; premenopausal (UMpre) and postmenopausal (UMpost). Erythrocyte copper-zinc superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx1) activities were measured along with plasma malondialdehyde (MDA) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) levels in patients with UM. The obtained data were compared to the data of healthy individuals (C, n = 25) and its subgroups; premenopausal (Cpre) and postmenopausal (Cpost). RESULTS: All AOE activities were higher (∼40% for Cu,Zn-SOD, p = 0.003; ∼55% for CAT, p = 0.001; ∼15% for GPx1, p = 0.169) and the LPO levels were lower (∼60% for MDA, p = 0.011 and ∼45% for 8-epi-PGF2α, p = 0.055) in patients with UM vs control. Approximately similar alterations were observed in UMpre vs Cpre and in UMpost vs Cpost. A significant negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels (r = -0.431, p = 0.005) was reported. CONCLUSION: Decreased LPO levels might be the consequence of compensator high antioxidant enzyme activities against mild oxidative stress in the circulation of patients with UM. The marked negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels also supported this finding.

Impaired antioxidant enzyme functions with increased lipid peroxidation in epithelial ovarian cancer.

We aimed to identify the possible role of oxidant-antioxidant status in epithelial ovarian cancer (EOC) by measuring (a) antioxidant enzyme (AOE) activities [total superoxide dismutase (SODtotal ), manganese-SOD (Mn-SOD), copper,zinc-SOD (Cu,Zn-SOD), catalase (CAT) and glutathione peroxidase (GPx1)], (b) Mn-SOD protein expression, (c) lipid peroxidation markers [malondialdehyde (MDA), 8-epi-prostaglandin-F2α (8-epi-PGF2α)] and by evaluating the possible correlations between tumor biomarkers, reproductive hormone levels and all measured parameters, comprehensively. The data obtained from the patients with EOC (M, n = 26) evaluated according to the histopathological/clinical characteristics of tumors and compared with data of healthy controls [Ctissue (C1) and Cblood/urine (C2), n = 30, respectively). Significantly, low activities of tumor SODtotal (52%), Mn-SOD (42%), Cu,Zn-SOD (55%); high activities of tumor and erythrocyte CAT (66%, 33% respectively) and tumor GPx1 (60%); high levels of tumor Mn-SOD protein expression; tumor MDA (193%) and urinary 8-epi-PGF2α (179%) were observed in serous EOC tumors (M1, n = 18) compared with controls (P < 0.05). However, higher levels of tumor MDA, Mn-SOD protein expression and urinary 8-epi-PGF2α were observed along with lower tumor CAT activity in poorly differentiated or undifferentiated (grade 3, G 3) versus well or moderately well differentiated (grade 1-2, G 1-2) serous EOC tumors. Obtained data indicate the presence of a severe redox imbalance in EOC and draw attention to the criticial role of AOEs in the pathogenesis of the disease. © 2017 IUBMB Life, 69(10):802-813, 2017.