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A large body of evidence supports the protective role of the flavonol antioxidant compound quercetin in mammals. We tested the hypothesis that quercetin can protect against the hypothalamus-pituitary-gonadal (HPG) axis defect like a reduction in gonadotropins and testicular hormones and abnormal semen analysis induced by chronic unpredictable stress (CUS), possibly via the downregulation of oxidative stress (ROS) and p53-Bax-caspase-3 pathways. Rats were either exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group) or were treated with quercetin (50 mg/kg body weight/day) at the same time the CUS were induced (treated group). Harvested testicular tissues were stained with basic histological staining, and testis homogenates were assayed for the tumor suppressor p53, apoptosis regulator Bax, B-cell lymphoma 2 (Bcl-2), caspase-3, malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, harvested epididymis tissues were used to assess semen analysis, and blood samples were assayed for the testicular hormone testosterone, the adrenal cortex hormone corticosterone, and the anterior pituitary gonadotropins, follicular stimulating hormone (FSH) and luteinizing hormone (LH). CUS induced profound testicular damage and significantly (p<0.05) induced p53, Bax, caspase-3, MDA, and corticosterone, which were significantly (p<0.05) inhibited by quercetin except corticosterone. Whereas, quercetin significantly (p<0.05) increased FSH, LH, testosterone, Bcl-2, GPx, and SOD levels that were inhibited by CUS. In addition, CUS induced oligozoospermia, asthenozoospermia, and teratozoospermia, which were significantly (p<0.05) protected by quercetin. Thus, Quercetin protects against CUS-induced HPG defects in rats, which is associated with the inhibition of ROS-p53-Bax-caspase-3 axis. [ABSTRACT FROM AUTHOR]

Repeated stress is a risk factor for memory impairment and neurological abnormalities in both humans and animals. We sought to investigate the extent of (i) brain tissue injury; (ii) nitrosative and oxidative stress in brain tissue homogenates; (iii) apoptotic and survival biomarkers in brain tissue homogenates; and (iv) immobility and climbing abilities, induced over a period of three weeks by chronic unpredictable stress (CUS). Wistar rats were either left untreated (Control group) or exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group). Assessment of depression-like behavior was performed and animals were then culled and harvested brain tissues were stained with basic histological staining and examined under light microscopy. In addition, brain tissue homogenates were prepared and assayed for these parameters; inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), superoxide dismutase (SOD), caspase-3, and B-cell lymphoma 2 (Bcl-2). Histology images showed CUS induced profound damage to the cerebral cortex as demonstrated by severe neuronal damage with shrunken cells, disrupted atrophic nuclei, perineuronal vacuolation and swollen glial cells. CUS also significantly (p<0.05) induced iNOS, MDA, and caspase-3, whereas SOD and Bcl-2 brain tissue levels were inhibited by CUS. In addition, data from the depression-like behavior, forced swimming test showed significant (p<0.05) increase in animal immobility and decrease in climbing ability in the model group of rats. Thus, here we demonstrated a reliable rat model of chronic stress-induced brain injury, which can further be used to investigate beneficial drugs or agents used for a period of three weeks to protect against CUS-induced brain damage. [ABSTRACT FROM AUTHOR]

We recently reported that chronic unpredictable stress (CUS) induced left ventricular dysfunction (LVD) in rats, which was inhibited by the cardioprotective agent quercetin. Based on these findings and because majority of patients with myocardial infarction (MI) can develop LVD and heart failure, we sought to produce an animal model of MI and LVD in rats and use this model to test the hypothesis that quercetin is able to prevent the potential MI induction by CUS. Rats were exposed to CUS using a variety of stressors in the presence and absence of quercetin (50 mg/kg body weight/day) for 21 days. Blood pressure and electrocardiogram (ECG) were recorded in all rat groups together with the examination of left ventricle (LV) tissue homogenates and sections to confirm the production of the animal model. We further extend on our recent findings on the role of apoptosis in the pathology of LVD and eventually MI. Blood pressure measurements and ECG recording confirmed the development of systemic hypertension and MI in the model group of rats exposed to CUS. In addition, histological staining confirmed that LV damages occurred in the same group. Furthermore, the proapoptotic gene Bax and the inflammatory biomarkers, TNF-α and IL-6 were augmented in LV homogenates by CUS. Simultaneous quercetin treatment lowered blood pressure and substantially prevented MI since it blocked the elevation of ST segment on the ECG and maintained a normal ECG reading. Quercetin suppressed the expression of Bax RNA messages, and significantly (p<0.05) blocked CUS-induced TNF-α and IL-6 upregulation. Thus, CUS induced MI in rats associated with augmentation of tissue injury biomarkers were prevented by quercetin, which further endorses our recent findings of a potential therapeutic role for quercetin in CUS induced cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Complications of chronic stress including cardiovascular disease are among the common public health problems that affect the lives of millions of people around the globe. We sought to determine whether the anti-oxidant and anti-apoptotic agent, quercetin can inhibit chronic stress-induced left ventricular dysfunction (LVD). Chronic unpredictable stress (CUS) was induced in rats using a variety of stressors in the presence and absence of quercetin (50 mg/kg body weight/day). Harvested tissues from the left ventricles (LV) of these animals were examined using basic histological staining. In addition, LV tissue homogenates were assayed for markers of oxidative and anti-oxidative stress that are known to be modulated in cardiac dysfunction. Furthermore, LV pressure was monitored by a pressure catheter inserted directly into the LV. Histopathological examinations of the LV in the model group (CUS) showed a profound damage to LV compared to the control group as demonstrated by a severe damage of cardiomyocytes and an increase of inflammatory cell infiltration, which was prevented by quercetin. CUS increased LV end-diastolic pressure that was significantly blocked by quercetin. In addition, quercetin significantly (p<0.05) blocked CUS-induced inhibition of the anti-oxidant superoxide dismutase (SOD) and the survival Bcl-2 proteins. Quercetin also significantly (p<0.05) inhibited CUS-induced augmentation of the oxidative stress TBARS and the apoptotic protein caspase-3. We conclude that LVD induced by CUS possibly via activation of oxidative and apoptosis pathways can be inhibited by quercetin; thus may offer therapeutic potential in humans. [ABSTRACT FROM AUTHOR]

Chronic stress by immobilization during pregnancy may cause alterations in mechanisms maintaining homeostasis in the adrenal gland. The objective of this study was to quantify cellular proliferation index in the adrenal cortex during pregnancy second half and assess the effects of chronic stress on it. Adrenal cortex proliferation index in stressed rats showed a significant decrease at 12 and 17 days of gestation, while at day 21 it did not show differences with the control treatments. Moreover, proliferation index of reticular zones in control and experimental rats, exhibited a significant reduction in comparison to glomerular and fascicular zones of adrenal cortex during the three gestation days studied. In conclusion, chronic stress by immobilization produces a decrease in cellular proliferation index at 12 and 17 gestation days, which may be related to changes in plasmatic concentrations of corticosterone and prolactin and, to the reduction of specific growth factors. Furthermore, the observed proliferation diminishment in reticular zone regarding the other cortical zones would be consistent with the migration theory of adrenal cells. [ABSTRACT FROM AUTHOR]

The chronic stress induces functional adaptations in the hypothalamo-pituitary- adrenocortical (HPA) and in the sympathetic-medullary-adrenal axis (SAM). Both axis are considered vital regulators of the homeostasis in vertebrates (Seyle, 1936; Ostrandrer et a!., 2006. On the other hand, the placenta provides highly specialized functions during gestation that are critical for the normal development of the eiribryo/fetus (Soares eta!., 1991). We hypothesized that the chronic immobilization (IMO) stress in pregnancy rats produces alterations in prolactin concentrations in placental tissue and also changes in the response of SAM axis. Chronic stress by IMO was applied on days 12, 17 and 21 of pregnancy rats. Relative concentrations and localization of placental lactogen-Il (PL-ll) and the PRL- like protein A (PLP-A) in chorioalantoic placenta were estimated by Immunoblotting and Immunocytochemical analysis. The levels of catecholamines metabolite, acid 3-metoxi 4-hidroximandélico (VMA), were analyzed in stressed rats urines on 6,12,17,21 days of pregnancy, by HPLC, in order to determine the response of SAM axis. During the days of the pregnancy studied, chronic stress did not induce any changes neither in the localization nor in placental concentrations of PL-II and PLP-A. The VMA values in stressed mothers urines increased on the day 6 respecting the control ones at the same time of pregnancy. VMA values in stressed rats at 21 days of pregnancy are smaller than the respective controls. We conclude that the chronic stressed mothers activated the SAM axis at the beginning of pregnancy and then they diminished the metabolites catecholamines that were interpreted as a stress adaptation coincident with normal concentrations of both placentary prolactines at this stage of the pregnancy. [ABSTRACT FROM AUTHOR]