Estrogen plus progestin increase superoxide dismutase and total antioxidant capacity in postmenopausal women.

OBJECTIVE: This cross-sectional study aimed to evaluate the behavior of blood antioxidant enzymes (superoxide dismutase (SOD), catalase and glutathione peroxidase), plasma total antioxidant capacity and oxidative damage (lipid oxidation and protein carbonyl levels) and their relationship with the serum levels of steroid hormones in premenopausal and postmenopausal women without and with estrogen alone (ET) or estrogen plus progestin therapy (EPT). METHODS: Blood was collected from four groups of subjects: premenopausal women (n = 24), postmenopausal women without hormone therapy (n = 31), postmenopausal women with ET (n = 12) and postmenopausal women with EPT (n = 16). RESULTS: The activities of the different SOD isoforms (CuZnSOD and MnSOD) and the plasma total antioxidant power were significantly higher in the postmenopausal women under EPT than in the postmenopausal women without hormone replacement therapy (HRT). Only CuZnSOD activity was increased in women receiving ET compared to the postmenopausal women without HRT. However, no differences were observed in the levels of lipid or protein oxidation or in the non-enzymatic plasma antioxidants (uric acid and albumin) among the groups. The duration of HRT and serum estrogen levels were positively correlated to the blood CuZnSOD activity and to plasma total antioxidant power, whereas the serum progesterone levels were positively correlated to CuZnSOD activity and negatively correlated to protein carbonyl groups. Interestingly, the total antioxidant power of plasma was positively correlated to CuZnSOD and glutathione peroxidase activities. CONCLUSION: We conclude that EPT increases blood MnSOD and CuZnSOD activity in postmenopausal women, leading to an increased plasma total antioxidant capacity. This finding may be relevant to the prevention of oxidative stress-related disorders in postmenopausal women.

Association between advanced oxidation protein products and 5-year mortality risk among amazon riparian elderly population.

Proteins are important targets of several modifications caused by oxidative stress, leading to structural changes and consequently partial or total loss of their functions. The oxidized proteins include advanced oxidation protein products (AOPP) derived from oxidation-modified albumin, as well as fibrinogen and lipoproteins. An increase in AOPP levels indicates an oxidative stress state and the presence of coexisting inflammation. Several investigations have also suggested an association between high AOPP levels and aging-related diseases. However, the link between elevated AOPP levels and elderly mortality risk has not yet been investigated. Here, we report on a 5-year longitudinal study that investigated the potential association between AOPP levels and mortality using a population-based representative sample of riparian elders living in Brazilian Amazon region (Maués-AM). Age, sex, socioeconomic and cultural conditions, chronic morbidities, polypharmacy, and previous morbidities were also tested as potential confounders. The AOPP levels were measured in 540 (84.78%) individuals, all of whom were followed over a 5-year period in order to establish the mortality rate. Within this study period, 74 (13.7%) elders died and 466 (86.3%) survived. The AOPP levels were higher among the elders who died within the 5-year period (46.27 ± 40.6 mmol/L) compared with those who survived (36.79 ± 20.84 mmol/L) (p = 0.002). The analysis confirmed the link between high AOPP levels and mortality risk, independent of other intervenient factors. These results suggest that elevated AOPP levels could be used to predict mortality risk in elderly patients.

Non-genomic, direct modulatory effect of 17ß-estradiol, progesterone and their synthetic derivatives on the activity of human erythrocyte CuZn superoxide dismutase.

This study aimed to evaluate whether natural or synthetic steroid hormones could directly modulate the activity of the different superoxide dismutase (SOD) isoforms found in human blood fractions without changing enzyme expression. Enzyme samples of human erythrocytes, the human platelet-rich plasma fraction (PRP) or isolated CuZnSOD, which was purified from human erythrocytes were pre-incubated with natural steroids (17ß-estradiol 17-acetate and progesterone) and their synthetic derivatives (ß-estradiol 3-benzoate and medroxyprogesterone 17-acetate). Then, CuZn and MnSOD activities were measured using the xanthine/xanthine oxidase/nitroblue tetrazolium method. Hormones had no effect on MnSOD activity from the PRP, but we show for the first time that natural and synthetic steroid hormones have a direct, bell-shaped effect on the activity of CuZnSOD from both male and female human erythrocytes. Low (physiological) hormone concentrations caused a dose-dependent increase in enzyme activity, which disappeared at higher hormone concentrations. In addition, the combination of synthetic and natural estrogens and progestins had a synergistic stimulatory effect on the activity of CuZnSOD from human erythrocytes. The molecular interaction between CuZnSOD and steroid hormones was preliminarily studied. Natural hormones did not change the electrophoretic mobility of SOD under denaturing conditions, but they did increase the absorption spectra of SOD in the 230-290 nm range. These data suggest that hormone-mediated modulation of CuZnSOD is related to subtle changes in protein conformation, possibly related to Trp and Phe residues. We propose that this effect may account for the physiological regulation of enzyme activity during conditions where steroid hormones undergo alterations as the ovulatory cycle.