Regulation of antioxidant enzyme activities in female rat brain by ovarian steroids

The sex steroids produce their effects by acting on numerous target tissues and organs, such as the reproductive organs, bone tissue and cartilage, peripheral blood vessels as well as the central nervous system (CNS). In our studies we have monitored the change of enzyme activity of the antioxidant (AO) system in the brain of female rats depending on the ovarian steroids. We have chosen it as a new parameter that might represent an important indicator of the changes within the CNS, bearing in mind the biological importance of the enzymes of the AO system. The experimental results of our study indicate that the enzyme activity of the AO system in the brain tissue of female rats shows a certain dependence on the concentration of ovarian hormones, progesterone and estradiol, in the organism. Study of the activity of the enzymes of the AO system in the brain of female rats depending on the influence of ovarian hormones can answer whether the action of ovarian steroids on the CNS includes maintenance of a dynamic equilibrium of free radicals in the neurons

Differential activation of JNK in rat hippocampus following acute and/or chronic stressors.

c-Jun N-terminal kinase (JNK) is activated by phosporylation in response to cellular stressors and extracellular signals and plays a role in the activation of glucocorticoid receptor (GR) and contributes to the stress-induced apoptosis. Therefore, the expression protein pattern of the active forms of cytosolic phospho- JNK (P-JNK) and inactive JNK in hippocampus of rats exposed to 21daily isolation as chronic stressor, sole and in combination with 2hrs acute stressors of immobilization (IM) or cold (4oC), were followed by Western blot. Concentration of serum corticosterone was monitored. We found significant increase in the levels of P-JNK following acute IM. Decreased levels of P-JNK following chronic isolation and when isolation preceded the application of acute IM were found, compared to its level after acute IM. Data suggest that diminished expresion of PJNK level following chronic isolation in hippocampus, might be involved in deregulation of intracellular GR negative feedback control as well as stress-induced apoptosis.Physical chemistry 2008 : 9th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 24-28 September 200

The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

The sensitivity of copper,zinc (CuZn)- and manganese (Mn)-superoxide dismutase (SOD) to exogenous estradiol benzoate (EB) was investigated in Wistar rats during postnatal brain development. Enzyme activities were measured in samples prepared from brains of rats of both sexes and various ages between 0 and 75 days, treated sc with 0.5 mug EB/100 g body weight in 0.1 ml olive oil/100 g body weight, 48 and 24 h before sacrifice. In females, EB treatment stimulated MnSOD activity on days 0 (66.1%), 8 (72.7%) and 15 (81.7%). In males, the stimulatory effect of EB on MnSOD activity on day 0 (113.6%) disappeared on day 8 and on days 15. and 45 it became inhibitory (40.3 and 30.5%, respectively). EB had no effect on the other age groups. The stimulatory effect of EB on CuZnSOD activity in newborn females (51.8%) changed to an inhibitory effect on day 8 (38.4%) and disappeared by day 45 when inhibition was detected again (48.7%). In males, the inhibitory effect on this enzyme was observed on days 0 (45.0%) and 15 (28.9%), and then disappeared until day 60 when a stimulatory effect was observed (38.4%). EB treatment had no effect on the other age groups. The sensitivity of MnSOD to estradiol differed significantly between sexes during the neonatal and prepubertal period, whereas it followed a similar pattern thereafter. The sensitivity of CuZnSOD to estradiol differed significantly between sexes during most of the study period. Regression analysis showed that the sensitivity of MnSOD to this estrogen tended to decrease similarly in both sexes, whereas the sensitivity of CuZnSOD showed a significantly different opposite tendency in female and male rats. These are the first reports indicating hormonal modulation of antioxidant enzyme activities related to the developmental process

Lithium Modulates the Chronic Stress-Induced Effect on Blood Glucose Level of Male Rats

In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li) and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism

Changes of Hippocampal Noradrenergic Capacity in Stress Condition

This study aimed to investigate the effects of chronic restraint stress (CRS) on the protein levels of dopamine-β-hydroxylase (DBH), noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2) and brain-derived neurotrophic factor (BDNF), as well as the concentration of noradrenaline (NA) in the rat hippocampus. The investigated parameters were quantified by Western blot analyses and ELISA kits. We found that CRS increased the protein levels of DBH by 30 %, VMAT2 by 11 %, BDNF by 11 % and the concentration of NA by 104 %, but decreased the protein levels of NET by 16 % in the hippocampus of chronically stressed rats. The molecular mechanisms by which CRS increased the hippocampal NA level are an important adaptive phenomenon of the noradrenergic system in the stress condition. © 2020 Charles University. All rights reserved

Effects of acute stress on gene expression of splenic catecholamine biosynthetic enzymes in chronically stressed rats

The aim of this study was to examine how acute immobilization stress affects the concentrations of catecholamines in the plasma and the expression of the splenic catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine-Я-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in chronically socially isolated rats. We found that acute immobilization increases the plasma catecholamine levels and splenic PNMT protein levels in chronically socially isolated rats. These results show that acute stress of chronically stressed animals activates the sympatho-adrenomedullary system and increases synthesis of splenic PNMT by 37%, both of which can modulate the immune function. [Projekat Ministarstva nauke Republike Srbije, br. III 41027, br. III 41022 and br. ON 173044

Antioxidant Status and Sex Hormones in Women with Simple Endometrial Hyperplasia

Cancer of the reproductive tract is an important source of morbidity and mortality among women worldwide. Factors affecting endometrial cancer and endometrial hyperplasia are known to be similar. Endometrial hyperplasia is abnormal proliferation of the glands and the stroma resulting in architectural and cytological modifications. Due to hormonal changes, this condition is most common among women who are nearing the menopause or have reached the menopause. Antioxidant system has a role in preventing cancer initiation and promotion. Since the carcinogenesis occurs in several stages, it is likely that the antioxidant defense depends on the type of cell and tissue. The objective of this study was to investigate whether antioxidant enzymes activities and lipid hydroperoxides concentration in patients with endometrial hyperplasia are influenced by the changes in sex hormones level (estradiol, progesterone, FSH, and LH) during the menstrual cycle and in postmenopause. The material we used consisted of blood and endometrial tissue specimens of women diagnosed with endometrial hyperplasia simplex. Patients were divided in groups depending on the phase of the menstrual cycle: follicular phase, luteal phase and postmenopause. The activities of antioxidant enzymes and the lipid hydroperoxides level were compared among the phases to test the differences and a linear regression model was used to evaluate the associations between hormone levels and antioxidant/oxidant variables. In the blood of examined patients, we observed a phase-related changes of LOOH concentrations. Significant negative correlation between FSH concentration and GR activity (r= -0.42, p<0.05) and significant positive correlation between LH and LOOH concentrations (r= 0.038, p<0.05) was found. In hyperplasia simplex tissue we recorded significant phase-related changes of LOOH level as well as of AO enzyme activities. SOD and CAT had similar activity pattern, which was higher in luteal phase and in postmenopause, compared to follicular phase (p<0.05). GPx and GR activities did not show any statistical difference. Also, negative correlation between progesterone and GR activity (r=-0.036, p<0.05) was observed. Hormonal influence on AO system is of importance in gynecological diseases etiology since they may promote cell proliferation but are also used in conservative therapy, especially for hyperplasia simplex. However, the role of ROS production as a risk factor for endometrial hyperplasia still needs to be clarified as well as the role of AO status in response to gonadotropins and sex steroids

Antioxidant Enzymes in Women with Hyperplasia Complex: Relation with Sex Hormones

Endometrial hyperplasia complex is gynecological disorder characterized by morphological irregularities of glands shape and size. Antioxidant enzymes (AOE), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), have an essential role in preventing oxidative damage in cell caused by reactive oxygen species (ROS). In this study, we examined the AO status in hyperplastic tissue of patients in menstrual cycle (follicular and luteal phase) and in postmenopause, as well as the relationship between sex hormones and AO parameters. The phase-related activity of GPx and GR in examined patients was significantly different than in healthy women. A significant negative correlation between FSH/LH level and GPx activiy was observed. Endometrial hyperplasias are considered as precancerous lesions and are treated either conservatively or surgicaly, and also by radiation therapy. Since the effects of these therapies are associated with AO and hormonal changes, our results may contribute to the prediction of potential therapeutic efficacy and to selection of the most effective treatment for hyperplasia complex.3rd International Conference on Radiation and Applications in Various Fields of Research (RAD), Jun 08-12, 2015, Budva, Montenegr

Animal Models for Chronic Stress-Induced Oxidative Stress in the Spleen: The Role of Exercise and Catecholaminergic System

We examined the effects of daily exercise on the gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and phenyl ethanolamine N-methyltransferase (PNMT)), vesicular monoamine transporter 2 (VMAT 2), antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), concentrations of catecholamines (noradrenaline (NA) and adrenaline (A)) and malondialdehyde (MDA), activities of monoamine oxidase (MAO), and antioxidant enzymes in the spleen of chronically psychosocially stressed rats. Exposure of chronically stressed rats to exercise increased the levels of PNMT protein by 19%, VMAT 2 mRNA by 100%, NA by 160%, and A by 140%; decreased/unchanged MAO enzyme activity; returned concentrations of MDA to control level; and increased CAT and GPx mRNA levels (50% and 150%, respectively). Exercise induced the accumulation of the catecholamines and a decrease of stress-induced oxidative stress in the spleen, which may significantly affect the immune-neuroendocrine interactions in stress conditions. Also, exercise induced the catecholaminergic system and antioxidant defense to become more ready to a novel stressor, which indicates that exercise may induce potentially positive physiological adaptations. Our combined model of chronic social isolation and long-term daily treadmill running in rats may be a good animal model in the research of therapeutic role of exercise in human disease caused by chronic stress

Stress-induced alternations of CuZn- and Mn- superoxide dismutase activity in rat liver

Superoxide dismutases (SODs) represent the first line of antioxidant defense and any alternation in their function might be potentially damaging. Therefore, changes of the CuZnSOD activity in cytosolic and nuclear fractions and MnSOD activity in mitochondrial fraction in liver of male rats exposed to 2h of either immobilization (IM) or cold (4°) as acute stressors, 21 day of social isolation (IS) as chronic stress, or their combination (acute+chronic stress), were investigated. Serum corticosterone (CORT) level was monitored as a stress marker. Acute stress IM with elevated CORT level led to increased CuZnSOD activity in nuclear fraction. Chronic isolation, where CORT was close to control value did not change the CuZnSOD activity neither in nuclei nor cytosol fraction, while combined stress IS+Cold led to increased cytosolic CuZnSOD activity. MnSOD activity in mitochondrial fraction was decreased in all treated groups. Data indicate that unchanged or increased cytosolic or nuclear CuZnSOD activity after different stressors mediate liver restoration of homeostasis, while decrease of mitochondrial MnSOD activity may results in cellular injury and inefficient ROS defense